{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:18:11Z","timestamp":1791389891755,"version":"4.3.3"},"reference-count":216,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>African trypanosomiasis is a neglected tropical disease caused by <jats:italic>Trypanosoma brucei<\/jats:italic> (<jats:italic>T. brucei<\/jats:italic>) and spread by the tsetse fly in sub-Saharan Africa. The trypanosome relies on heat shock proteins for survival in the insect vector and mammalian host. Heat shock protein 90 (HSP90) plays a crucial role in the stress response at the cellular level. Inhibition of its interactions with chaperones and co-chaperones is being explored as a potential therapeutic target for numerous diseases. This study provides an <jats:italic>in silico<\/jats:italic> overview of HSP90 and its co-chaperones in both <jats:italic>T. brucei brucei<\/jats:italic> and <jats:italic>T. brucei gambiense<\/jats:italic> in relation to human and other trypanosomal species, including non-parasitic <jats:italic>Bodo saltans<\/jats:italic> and the insect infecting <jats:italic>Crithidia fasciculata<\/jats:italic>. A structural analysis of <jats:italic>T. brucei<\/jats:italic> HSP90 revealed differences in the orientation of the linker and C-terminal domain in comparison to human HSP90. Phylogenetic analysis displayed the <jats:italic>T. brucei<\/jats:italic> HSP90 proteins clustering into three distinct groups based on subcellular localizations, namely, cytosol, mitochondria, and endoplasmic reticulum. Syntenic analysis of cytosolic <jats:italic>HSP90<\/jats:italic> genes revealed that <jats:italic>T. b. brucei<\/jats:italic> encoded for 10 tandem copies, while <jats:italic>T. b. gambiense<\/jats:italic> encoded for three tandem copies; <jats:italic>Leishmania major (L. major)<\/jats:italic> had the highest gene copy number with 17 tandem copies. The updated information on HSP90 from recently published proteomics on <jats:italic>T. brucei<\/jats:italic> was examined for different life cycle stages and subcellular localizations. The results show a difference between <jats:italic>T. b. brucei<\/jats:italic> and <jats:italic>T. b. gambiense<\/jats:italic> with <jats:italic>T. b. brucei<\/jats:italic> encoding a total of twelve putative <jats:italic>HSP90<\/jats:italic> genes, while <jats:italic>T. b. gambiense<\/jats:italic> encodes five <jats:italic>HSP90<\/jats:italic> genes. Eighteen putative co-chaperones were identified with one notable absence being cell division cycle 37 (Cdc37). These results provide an updated framework on approaching HSP90 and its interactions as drug targets in the African trypanosome.<\/jats:p>","DOI":"10.3389\/fmolb.2022.947078","type":"journal-article","created":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T11:29:08Z","timestamp":1663932548000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["In silico analysis of the HSP90 chaperone system from the African trypanosome, Trypanosoma brucei"],"prefix":"10.3389","volume":"9","author":[{"given":"Miebaka","family":"Jamabo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen John","family":"Bentley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Macucule-Tinga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praise","family":"Tembo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne Lesley","family":"Edkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aileen","family":"Boshoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5497","DOI":"10.1002\/pmic.200900354","article-title":"Protein composition of Trypanosoma brucei mitochondrial membranes","volume":"9","author":"Acestor","year":"2009","journal-title":"Proteomics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"M110006908","DOI":"10.1074\/mcp.M110.006908","article-title":"Trypanosoma brucei mitochondrial respiratome: Composition and organization in procyclic form","volume":"10","author":"Acestor","year":"2011","journal-title":"Mol. Cell. Proteomics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1257\/aer.20130604","article-title":"The effect of the TseTse fly on african development","volume":"105","author":"Alsan","year":"2015","journal-title":"Am. Econ. Rev."},{"key":"B4","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1101\/gr.115089.110","article-title":"High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome","volume":"21","author":"Alsford","year":"2011","journal-title":"Genome Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/j.bbamcr.2011.08.007","article-title":"TRAP-1, the mitochondrial Hsp90","volume":"1823","author":"Altieri","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1645\/GE-916R1.1","article-title":"Functional characterization of the serine\/threonine protein phosphatase 5 from Trypanosoma brucei","volume":"92","author":"Anderson","year":"2006","journal-title":"J. Parasitol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.tcb.2005.09.003","article-title":"Modulating molecular chaperone Hsp90 functions through reversible acetylation","volume":"15","author":"Aoyagi","year":"2005","journal-title":"Trends Cell Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1006\/scdb.1999.0320","article-title":"GRP94, an ER chaperone with protein and peptide binding properties","volume":"10","author":"Argon","year":"1999","journal-title":"Semin. Cell Dev. Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"D457","DOI":"10.1093\/nar\/gkp851","article-title":"TriTrypDB: A functional genomic resource for the trypanosomatidae","volume":"38","author":"Aslett","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"11099","DOI":"10.1074\/jbc.REV120.011833","article-title":"Post-translational modifications of Hsp90 and translating the chaperone code","volume":"295","author":"Backe","year":"2020","journal-title":"J. Biol. Chem."},{"key":"B11","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/978-3-319-11731-7_3","article-title":"Hsp70\/Hsp90 organising protein (hop): Beyond interactions with chaperones and prion proteins","volume":"78","author":"Baindur-Hudson","year":"2015","journal-title":"Subcell. Biochem."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1894","DOI":"10.1016\/j.celrep.2019.07.045","article-title":"Co-Chaperones TIMP2 and AHA1 competitively regulate extracellular HSP90:client MMP2 activity and matrix proteolysis","volume":"28","author":"Baker-Williams","year":"2019","journal-title":"Cell Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1093\/bmb\/lds031","article-title":"Management of trypanosomiasis and leishmaniasis","volume":"104","author":"Barrett","year":"2012","journal-title":"Br. Med. Bull."},{"key":"B14","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1111\/febs.13141","article-title":"Identification of two p23 co-chaperone isoforms in Leishmania braziliensis exhibiting similar structures and Hsp90 interaction properties despite divergent stabilities","volume":"282","author":"Batista","year":"2015","journal-title":"FEBS J."},{"key":"B15","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1093\/emboj\/cdg065","article-title":"Elucidation of tRNA-dependent editing by a class II tRNA synthetase and significance for cell viability","volume":"22","author":"Beebe","year":"2003","journal-title":"EMBO J."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1002\/pmic.200300462","article-title":"Developmentally induced changes of the proteome in the protozoan parasite Leishmania donovani","volume":"3","author":"Bente","year":"2003","journal-title":"PROTEOMICS"},{"key":"B17","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s12192-018-0950-x","article-title":"The Hsp70\/J-protein machinery of the African trypanosome, Trypanosoma brucei","volume":"24","author":"Bentley","year":"2019","journal-title":"Cell Stress Chaperones"},{"key":"B18","doi-asserted-by":"publisher","first-page":"5975","DOI":"10.1038\/s41467-020-19783-w","article-title":"The Hsp70-Hsp90 co-chaperone Hop\/Stip1 shifts the proteostatic balance from folding towards degradation","volume":"11","author":"Bhattacharya","year":"2020","journal-title":"Nat. Commun."},{"key":"B19","doi-asserted-by":"publisher","first-page":"5765","DOI":"10.4049\/jimmunol.1401417","article-title":"Functions of heat shock proteins in pathways of the innate and adaptive immune system","volume":"193","author":"Binder","year":"2014","journal-title":"J. Immunol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1002\/(SICI)1521-1878(199911)21:11<932::AID-BIES5>3.0.CO;2-N","article-title":"The tetratricopeptide repeat: A structural motif mediating protein-protein interactions","volume":"21","author":"Blatch","year":"1999","journal-title":"BioEssays"},{"key":"B21","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S0014-5793(01)02177-9","article-title":"Nuclear localization of protein phosphatase 5 is dependent on the carboxy-terminal region","volume":"491","author":"Borthwick","year":"2001","journal-title":"FEBS Lett."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1126\/science.274.5293.1715","article-title":"Chaperone function of hsp90-associated proteins","volume":"274","author":"Bose","year":"1996","journal-title":"Science"},{"key":"B23","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1042\/bj3100225","article-title":"High constitutive levels of heat-shock proteins in human-pathogenic parasites of the genus Leishmania","volume":"310","author":"Brandau","year":"1995","journal-title":"Biochem. J."},{"key":"B24","doi-asserted-by":"publisher","first-page":"19265","DOI":"10.1074\/jbc.M109002200","article-title":"Ligand discrimination by TPR domains: Relevance and selectivity of EEVD-RECOGNITION in Hsp70\u00b7Hop\u00b7Hsp90 complexes","volume":"277","author":"Brinker","year":"2002","journal-title":"J. Biol. Chem."},{"key":"B25","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1038\/nature04541","article-title":"Flagellar motility is required for the viability of the bloodstream trypanosome","volume":"440","author":"Broadhead","year":"2006","journal-title":"Nature"},{"key":"B26","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/S0140-6736(09)60829-1","article-title":"Human african trypanosomiasis","volume":"375","author":"Brun","year":"2010","journal-title":"Lancet"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3613","DOI":"10.1093\/emboj\/cdg362","article-title":"Cofactor Tpr2 combines two TPR domains and a J domain to regulate the Hsp70\/Hsp90 chaperone system","volume":"22","author":"Brychzy","year":"2003","journal-title":"EMBO J."},{"key":"B28","doi-asserted-by":"publisher","first-page":"106","DOI":"10.4103\/2319-4170.113230","article-title":"Structure, function and regulation of the Hsp90 machinery","volume":"36","author":"Buchner","year":"2013","journal-title":"Biomed. J."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2397","DOI":"10.1016\/S0140-6736(17)31510-6","article-title":"Human african trypanosomiasis","volume":"390","author":"B\u00fcscher","year":"2017","journal-title":"Lancet"},{"key":"B30","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1074\/mcp.M112.019224","article-title":"Comparative proteomics of two life cycle stages of stable isotope-labeled Trypanosoma brucei reveals novel components of the parasite\u2019s host adaptation machinery","volume":"12","author":"Butter","year":"2013","journal-title":"Mol. Cell. Proteomics"},{"key":"B31","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1006\/excr.2000.4983","article-title":"Immunoelectron microscopy provides evidence that tumor necrosis factor receptor-associated protein 1 (TRAP-1) is a mitochondrial protein which also localizes at specific extramitochondrial sites","volume":"260","author":"Cechetto","year":"2000","journal-title":"Exp. Cell Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"4872","DOI":"10.1128\/MCB.00711-13","article-title":"A multiple aminoacyl-tRNA synthetase complex that enhances tRNA-aminoacylation in african trypanosomes","volume":"33","author":"Cestari","year":"2013","journal-title":"Mol. Cell. Biol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1128\/MCB.17.1.318","article-title":"In vivo analysis of the Hsp90 cochaperone Sti1 (p60)","volume":"17","author":"Chang","year":"1997","journal-title":"Mol. Cell. Biol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.ygeno.2005.08.012","article-title":"The HSP90 family of genes in the human genome: Insights into their divergence and evolution","volume":"86","author":"Chen","year":"2005","journal-title":"Genomics"},{"key":"B35","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1186\/1471-2164-7-156","article-title":"Comparative genomics and evolution of the HSP90 family of genes across all kingdoms of organisms","volume":"7","author":"Chen","year":"2006","journal-title":"BMC Genomics"},{"key":"B36","doi-asserted-by":"publisher","first-page":"32315","DOI":"10.1074\/jbc.271.50.32315","article-title":"The tetratricopeptide repeat domain of protein phosphatase 5 mediates binding to glucocorticoid receptor heterocomplexes and acts as a dominant negative mutant","volume":"271","author":"Chen","year":"1996","journal-title":"J. Biol. Chem."},{"key":"B37","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/S1043-2760(00)00335-0","article-title":"Protein phosphatase 5 in signal transduction","volume":"12","author":"Chinkers","year":"2001","journal-title":"Trends Endocrinol. Metab."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1017\/S0031182013002084","article-title":"Co-chaperones of Hsp90 in Plasmodium falciparum and their concerted roles in cellular regulation","volume":"141","author":"Chua","year":"2014","journal-title":"Parasitology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"50","DOI":"10.4161\/cc.3.1.607","article-title":"The achilles heel of ErbB-2\/HER2: Regulation by the Hsp90 chaperone machine and potential for pharmacological intervention","volume":"3","author":"Citri","year":"2004","journal-title":"Cell Cycle"},{"key":"B40","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.molbiopara.2007.07.007","article-title":"Post-transcriptional regulation of gene expression in trypanosomes and leishmanias","volume":"156","author":"Clayton","year":"2007","journal-title":"Mol. Biochem. Parasitol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/S0968-0004(97)01060-8","article-title":"Novel protein serine\/threonine phosphatases: Variety is the spice of life","volume":"22","author":"Cohen","year":"1997","journal-title":"Trends biochem. Sci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"3275","DOI":"10.1002\/pmic.200500668","article-title":"Comparative proteomics of glycosomes from bloodstream form and procyclic culture form Trypanosoma brucei brucei","volume":"6","author":"Colasante","year":"2006","journal-title":"Proteomics"},{"key":"B43","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.ijbiomac.2018.06.123","article-title":"Structural and functional studies of the Leishmania braziliensis SGT co-chaperone indicate that it shares structural features with HIP and can interact with both Hsp90 and Hsp70 with similar affinities","volume":"118","author":"Coto","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e0001737","DOI":"10.1371\/journal.pone.0001737","article-title":"The human TPR protein TTC4 is a putative Hsp90 Co-chaperone which interacts with CDC6 and shows alterations in transformed cells","volume":"3","author":"Crevel","year":"2008","journal-title":"PLoS ONE"},{"key":"B45","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/S0163-7258(98)00013-8","article-title":"The 90-kDa molecular chaperone family: Structure, function, and clinical applications. A comprehensive review","volume":"79","author":"Csermely","year":"1998","journal-title":"Pharmacol. Ther."},{"key":"B46","doi-asserted-by":"publisher","first-page":"21170","DOI":"10.1074\/jbc.M800046200","article-title":"Intra- and intermonomer interactions are required to synergistically facilitate ATP hydrolysis in Hsp90","volume":"283","author":"Cunningham","year":"2008","journal-title":"J. Biol. Chem."},{"key":"B47","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1038\/nrg3055","article-title":"Controlling gene expression in response to stress","volume":"12","author":"de Nadal","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"B48","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s12192-020-01167-0","article-title":"Human Hsp90 cochaperones: Perspectives on tissue-specific expression and identification of cochaperones with similar in vivo functions","volume":"26","author":"Dean","year":"2021","journal-title":"Cell Stress Chaperones"},{"key":"B49","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.pt.2016.10.009","article-title":"TrypTag.org: A trypanosome genome-wide protein localisation resource","volume":"33","author":"Dean","year":"2017","journal-title":"Trends Parasitol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1007\/s40265-019-1051-6","article-title":"Fexinidazole: First global approval","volume":"79","author":"Deeks","year":"2019","journal-title":"Drugs"},{"key":"B51","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/978-1-59745-406-3_6","article-title":"High-yield isolation and subcellular proteomic characterization of nuclear and subnuclear structures from trypanosomes","volume":"463","author":"DeGrasse","year":"2008","journal-title":"Methods Mol. Biol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/0166-6851(87)90077-6","article-title":"The genome and the antigen gene repertoire of Trypanosoma brucei gambiense are smaller than those of T. b. brucei","volume":"26","author":"Dero","year":"1987","journal-title":"Mol. Biochem. Parasitol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1093\/molbev\/msq289","article-title":"Phylogenomic analysis of kinetoplastids supports that trypanosomatids arose from within bodonids","volume":"28","author":"Deschamps","year":"2011","journal-title":"Mol. Biol. Evol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"4458","DOI":"10.1093\/emboj\/cdf447","article-title":"LeishmaniaLPG3 encodes a GRP94 homolog required for phosphoglycan synthesis implicated in parasite virulence but not viability","volume":"21","author":"Descoteaux","year":"2002","journal-title":"EMBO J."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1980","DOI":"10.1093\/gbe\/evw140","article-title":"Species- and strain-specific adaptation of the HSP70 super family in pathogenic trypanosomatids","volume":"8","author":"Drini","year":"2016","journal-title":"Genome Biol. Evol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"e1003286","DOI":"10.1371\/journal.ppat.1003286","article-title":"Post-transcriptional regulation of the trypanosome heat shock response by a zinc finger protein","volume":"9","author":"Droll","year":"2013","journal-title":"PLoS Pathog."},{"key":"B57","doi-asserted-by":"publisher","first-page":"4659","DOI":"10.1091\/mbc.e07-05-0467","article-title":"Src-mediated phosphorylation of Hsp90 in response to vascular endothelial growth factor (VEGF) is required for VEGF receptor-2 signaling to endothelial NO synthase","volume":"18","author":"Duval","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"B58","doi-asserted-by":"publisher","first-page":"e26044","DOI":"10.1371\/journal.pone.0026044","article-title":"An interaction network predicted from public data as a discovery tool: Application to the Hsp90 molecular chaperone machine","volume":"6","author":"Echeverr\u00eda","year":"2011","journal-title":"PLOS ONE"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1128\/MCB.01099-15","article-title":"A remodeled Hsp90 molecular chaperone ensemble with the novel cochaperone Aarsd1 is required for muscle differentiation","volume":"36","author":"Echeverr\u00eda","year":"2016","journal-title":"Mol. Cell. Biol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1126\/science.1112631","article-title":"The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease","volume":"309","author":"El-Sayed","year":"","journal-title":"Science"},{"key":"B61","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1126\/science.1112181","article-title":"Comparative genomics of trypanosomatid parasitic Protozoa","volume":"309","author":"El-Sayed","year":"","journal-title":"Science"},{"key":"B62","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/S0378-1119(02)01021-1","article-title":"Phylogenetic relationships of organellar Hsp90 homologs reveal fundamental differences to organellar Hsp70 and Hsp60 evolution","volume":"299","author":"Emelyanov","year":"2002","journal-title":"Gene"},{"key":"B63","doi-asserted-by":"publisher","first-page":"3305","DOI":"10.1074\/jbc.275.5.3305","article-title":"The hsp90-related protein TRAP1 is a mitochondrial protein with distinct functional properties","volume":"275","author":"Felts","year":"2000","journal-title":"J. Biol. Chem."},{"key":"B64","doi-asserted-by":"publisher","first-page":"e333","DOI":"10.1371\/journal.pntd.0000333","article-title":"The burden of human african trypanosomiasis","volume":"2","author":"F\u00e8vre","year":"2008","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B65","doi-asserted-by":"publisher","first-page":"245","DOI":"10.2174\/1389203715666140331114233","article-title":"Protozoan HSP90-heterocomplex: Molecular interaction network and biological significance","volume":"15","author":"Figueras","year":"2014","journal-title":"Curr. Protein Pept. Sci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1111\/j.1574-6976.2007.00069.x","article-title":"A postgenomic view of the heat shock proteins in kinetoplastids","volume":"31","author":"Folgueira","year":"2007","journal-title":"FEMS Microbiol. Rev."},{"key":"B67","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1186\/1471-2164-13-531","article-title":"Comparative genomic analysis of human infective Trypanosoma cruzi lineages with the bat-restricted subspecies T. cruzi marinkellei","volume":"13","author":"Franz\u00e9n","year":"2012","journal-title":"BMC Genomics"},{"key":"B68","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1126\/science.274.5293.1718","article-title":"Molecular chaperone machines: Chaperone activities of the cyclophilin cyp-40 and the steroid aporeceptor-associated protein p23","volume":"274","author":"Freeman","year":"1996","journal-title":"Science"},{"key":"B69","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.2174\/1568026033451862","article-title":"Peptidylprolyl cis\/trans isomerases (immunophilins): Biological diversity - targets - functions","volume":"3","author":"Galat","year":"2003","journal-title":"Curr. Top. Med. Chem."},{"key":"B70","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1074\/mcp.M900261-MCP200","article-title":"A proteomic investigation of ligand-dependent HSP90 complexes reveals CHORDC1 as a novel ADP-dependent HSP90-interacting protein","volume":"9","author":"Gano","year":"2010","journal-title":"Mol. Cell. Proteomics"},{"key":"B71","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S0014-5793(02)03321-5","article-title":"p23 and HSP20\/alpha-crystallin proteins define a conserved sequence domain present in other eukaryotic protein families.","volume":"529","author":"Garcia-Ranea","year":"2002","journal-title":"FEBS Lett."},{"key":"B72","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1385\/1-59259-890-0:571","article-title":"Protein identification and analysis tools on the ExPASy server","volume-title":"The proteomics protocols handbook","author":"Gasteiger","year":"2005"},{"key":"B73","doi-asserted-by":"publisher","first-page":"e0005368","DOI":"10.1371\/journal.pntd.0005368","article-title":"TrypsNetDB: An integrated framework for the functional characterization of trypanosomatid proteins","volume":"11","author":"Gazestani","year":"2017","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B74","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/1756-3305-5-71","article-title":"The origins of the trypanosome genome strains Trypanosoma brucei brucei TREU 927, T. b. gambiense DAL 972, T. vivax Y486 and T. congolense IL3000","volume":"5","author":"Gibson","year":"2012","journal-title":"Parasit. Vectors"},{"key":"B75","doi-asserted-by":"publisher","first-page":"3626","DOI":"10.1038\/s41467-019-11518-w","article-title":"The Hsp90 isoforms from S. cerevisiae differ in structure, function and client range","volume":"10","author":"Girstmair","year":"2019","journal-title":"Nat. Commun."},{"key":"B76","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1007\/s10555-008-9125-z","article-title":"The role of serine\/threonine protein phosphatase type 5 (PP5) in the regulation of stress-induced signaling networks and cancer","volume":"27","author":"Golden","year":"2008","journal-title":"Cancer Metastasis Rev."},{"key":"B77","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/j.jmb.2004.11.071","article-title":"Characterization of Saccharomyces cerevisiae Nop17p, a novel nop58p-interacting protein that is involved in pre-rRNA processing","volume":"346","author":"Gonzales","year":"2005","journal-title":"J. Mol. Biol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"e0181884","DOI":"10.1371\/journal.pone.0181884","article-title":"The nuclear proteome of Trypanosoma brucei","volume":"12","author":"Goos","year":"2017","journal-title":"PLoS ONE"},{"key":"B79","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1128\/EC.1.6.936-943.2002","article-title":"Inhibition of HSP90 in trypanosoma cruzi induces a stress response but No stage differentiation","volume":"1","author":"Graefe","year":"2002","journal-title":"Eukaryot. Cell"},{"key":"B80","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1186\/1471-2164-13-556","article-title":"Proteome remodelling during development from blood to insect-form Trypanosoma brucei quantified by SILAC and mass spectrometry","volume":"13","author":"Gunasekera","year":"2012","journal-title":"BMC Genomics"},{"key":"B81","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1093\/oxfordjournals.molbev.a040281","article-title":"Phylogenetic analysis of the 90 kD heat shock family of protein sequences and an examination of the relationship among animals, plants, and fungi species","volume":"12","author":"Gupta","year":"1995","journal-title":"Mol. Biol. Evol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"2796","DOI":"10.1021\/pr401209w","article-title":"High-confidence glycosome proteome for procyclic form Trypanosoma brucei by epitope-tag organelle enrichment and SILAC proteomics","volume":"13","author":"G\u00fcther","year":"2014","journal-title":"J. Proteome Res."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.3390\/cancers6021065","article-title":"The double-edged sword: Conserved functions of extracellular hsp90 in wound healing and cancer","volume":"6","author":"Hance","year":"2014","journal-title":"Cancers (Basel)"},{"key":"B84","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/nature10317","article-title":"Molecular chaperones in protein folding and proteostasis","volume":"475","author":"Hartl","year":"2011","journal-title":"Nature"},{"key":"B85","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1016\/j.str.2018.06.002","article-title":"Deep structural analysis of RPAP3 and PIH1D1, two components of the HSP90 Co-chaperone R2TP complex","volume":"26","author":"Henri","year":"2018","journal-title":"Structure"},{"key":"B86","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.3390\/genes11101196","article-title":"Trypanosoma cruzi genome: Organization, multi-gene families, transcription, and biological implications","volume":"11","author":"Herreros-Cabello","year":"2020","journal-title":"Genes."},{"key":"B87","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1111\/cmi.12057","article-title":"The Hsp90-Sti1 interaction is critical for Leishmania donovani proliferation in both life cycle stages","volume":"15","author":"Hombach","year":"2013","journal-title":"Cell. Microbiol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"5074","DOI":"10.1038\/s41598-019-41640-0","article-title":"Leishmania donovani 90 kD heat shock protein \u2013 impact of phosphosites on parasite fitness, infectivity and casein kinase affinity","volume":"9","author":"Hombach-Barrigah","year":"2019","journal-title":"Sci. Rep."},{"key":"B89","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.celrep.2014.03.013","article-title":"Phosphorylation-dependent PIH1D1 interactions define substrate specificity of the R2TP cochaperone complex","volume":"7","author":"Ho\u0159ej\u0161\u00ed","year":"2014","journal-title":"Cell Rep."},{"key":"B90","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.3390\/ijms19092560","article-title":"The HSP90 family: Structure, regulation, function, and implications in health and disease","volume":"19","author":"Hoter","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"B91","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.3892\/or.2020.7565","article-title":"Ubiquitin specific peptidase 19 is a prognostic biomarker and affect the proliferation and migration of clear cell renal cell carcinoma","volume":"43","author":"Hu","year":"2020","journal-title":"Oncol. Rep."},{"key":"B92","doi-asserted-by":"publisher","first-page":"e86842","DOI":"10.1371\/journal.pone.0086842","article-title":"Hsp90 binds directly to fibronectin (FN) and inhibition reduces the extracellular fibronectin matrix in breast cancer cells","volume":"9","author":"Hunter","year":"2014","journal-title":"PLoS One"},{"key":"B93","doi-asserted-by":"publisher","first-page":"e658","DOI":"10.1371\/journal.pntd.0000658","article-title":"The genome sequence of trypanosoma brucei gambiense, causative agent of chronic human african trypanosomiasis","volume":"4","author":"Jackson","year":"2010","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B94","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/128_2012_356","article-title":"Hsp90: Structure and function","volume":"328","author":"Jackson","year":"2013","journal-title":"Top. Curr. Chem."},{"key":"B95","doi-asserted-by":"publisher","first-page":"17881","DOI":"10.1073\/pnas.1414073111","article-title":"The charged linker of the molecular chaperone Hsp90 modulates domain contacts and biological function","volume":"111","author":"Jahn","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B96","doi-asserted-by":"publisher","first-page":"14412","DOI":"10.1074\/jbc.270.24.14412","article-title":"Structural organization of procaryotic and eucaryotic Hsp90. Influence of divalent cations on structure and function","volume":"270","author":"Jakob","year":"1995","journal-title":"J. Biol. Chem."},{"key":"B97","doi-asserted-by":"publisher","first-page":"3679","DOI":"10.1074\/jbc.273.6.3679","article-title":"Hop modulates hsp70\/hsp90 interactions in protein folding","volume":"273","author":"Johnson","year":"1998","journal-title":"J. Biol. Chem."},{"key":"B98","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s12192-008-0058-9","article-title":"Plasticity of the Hsp90 chaperone machine in divergent eukaryotic organisms","volume":"14","author":"Johnson","year":"2009","journal-title":"Cell Stress Chaperones"},{"key":"B99","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.bbamcr.2011.09.020","article-title":"Evolution and function of diverse Hsp90 homologs and cochaperone proteins","volume":"1823","author":"Johnson","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"B100","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1007\/s00436-007-0817-z","article-title":"Protein phosphatase 5 is required for Hsp90 function during proteotoxic stresses in Trypanosoma brucei","volume":"102","author":"Jones","year":"2008","journal-title":"Parasitol. Res."},{"key":"B101","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1093\/bioinformatics\/8.3.275","article-title":"The rapid generation of mutation data matrices from protein sequences","volume":"8","author":"Jones","year":"1992","journal-title":"Comput. Appl. Biosci."},{"key":"B102","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1177\/1087057115569155","article-title":"Repurposing of the open access malaria box for kinetoplastid diseases identifies novel active scaffolds against trypanosomatids","volume":"20","author":"Kaiser","year":"2015","journal-title":"J. Biomol. Screen."},{"key":"B103","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s12192-008-0068-7","article-title":"Guidelines for the nomenclature of the human heat shock proteins","volume":"14","author":"Kampinga","year":"2009","journal-title":"Cell Stress Chaperones"},{"key":"B104","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1091\/mbc.e09-12-1017","article-title":"Biological and structural basis for Aha1 regulation of Hsp90 ATPase activity in maintaining proteostasis in the human disease cystic fibrosis","volume":"21","author":"Koulov","year":"2010","journal-title":"Mol. Biol. Cell"},{"key":"B105","doi-asserted-by":"publisher","first-page":"E2210","DOI":"10.1073\/pnas.1719969115","article-title":"Functional and physical interaction between yeast Hsp90 and Hsp70","volume":"115","author":"Kravats","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B106","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1111\/zph.12945","article-title":"Atypical human trypanosomosis: Potentially emerging disease with lack of understanding","volume":"69","author":"Kumar","year":"2022","journal-title":"Zoonoses Public Health"},{"key":"B107","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"Mega X: Molecular evolutionary genetics analysis across computing platforms","volume":"35","author":"Kumar","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"B108","doi-asserted-by":"publisher","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","article-title":"Clustal W and clustal X version 2.0","volume":"23","author":"Larkin","year":"2007","journal-title":"Bioinformatics"},{"key":"B109","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/S0165-2478(01)00331-5","article-title":"Antigenic properties of the Leishmania infantum GRP94 and mapping of linear B-cell epitopes","volume":"80","author":"Larreta","year":"2002","journal-title":"Immunol. Lett."},{"key":"B110","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1006\/expr.2000.4553","article-title":"Leishmania infantum: Gene cloning of the GRP94 homologue, its expression as recombinant protein, and analysis of antigenicity","volume":"96","author":"Larreta","year":"2000","journal-title":"Exp. Parasitol."},{"key":"B111","doi-asserted-by":"publisher","first-page":"D302","DOI":"10.1093\/nar\/gkr931","article-title":"Smart 7: Recent updates to the protein domain annotation resource","volume":"40","author":"Letunic","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"B112","doi-asserted-by":"publisher","first-page":"19214","DOI":"10.1073\/pnas.1209997109","article-title":"SGTA antagonizes BAG6-mediated protein triage","volume":"109","author":"Leznicki","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B113","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1016\/j.bbamcr.2011.09.003","article-title":"The Hsp90 chaperone machinery: Conformational dynamics and regulation by co-chaperones","volume":"1823","author":"Li","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"B114","doi-asserted-by":"publisher","first-page":"W60","DOI":"10.1093\/NAR\/GKAA443","article-title":"Fatcat 2.0: Towards a better understanding of the structural diversity of proteins","volume":"48","author":"Li","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"B115","doi-asserted-by":"publisher","first-page":"e38","DOI":"10.1016\/S1473-3099(19)30612-7","article-title":"New WHO guidelines for treatment of gambiense human african trypanosomiasis including fexinidazole: Substantial changes for clinical practice","volume":"20","author":"Lindner","year":"2020","journal-title":"Lancet. Infect. Dis."},{"key":"B116","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1002\/CBIC.202000699","article-title":"The charged linker modulates the conformations and molecular interactions of Hsp90","volume":"22","author":"L\u00f3pez","year":"2021","journal-title":"Chembiochem."},{"key":"B117","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1038\/s41467-018-03942-1","article-title":"RPAP3 provides a flexible scaffold for coupling HSP90 to the human R2TP co-chaperone complex","volume":"9","author":"Martino","year":"2018","journal-title":"Nat. Commun."},{"key":"B118","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1016\/j.bbamcr.2011.10.013","article-title":"GRP94: An HSP90-like protein specialized for protein folding and quality control in the endoplasmic reticulum","volume":"1823","author":"Marzec","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"B119","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3389\/fonc.2017.00058","article-title":"The chaperone TRAP1 as a modulator of the mitochondrial adaptations in cancer cells","volume":"7","author":"Masgras","year":"2017","journal-title":"Front. Oncol."},{"key":"B120","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1016\/S1097-2765(02)00793-1","article-title":"Aha, another regulator for Hsp90 chaperones","volume":"10","author":"Mayer","year":"2002","journal-title":"Mol. Cell"},{"key":"B121","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1016\/j.jmb.2005.11.085","article-title":"The Co-chaperone p23 arrests the Hsp90 ATPase cycle to trap client proteins","volume":"356","author":"McLaughlin","year":"2006","journal-title":"J. Mol. Biol."},{"key":"B122","doi-asserted-by":"publisher","first-page":"e00056","DOI":"10.1128\/AAC.00056-18","article-title":"Model system identifies kinetic driver of Hsp90 inhibitor activity against african trypanosomes and plasmodium falciparum","volume":"62","author":"Meyer","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"B123","doi-asserted-by":"publisher","first-page":"e0063221","DOI":"10.1128\/AAC.00632-21","article-title":"Cytosolic and mitochondrial Hsp90 in cytokinesis, mitochondrial DNA replication, and drug action in trypanosoma brucei","volume":"65","author":"Meyer","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"B124","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1093\/infdis\/jit179","article-title":"Potent antitrypanosomal activities of heat shock protein 90 inhibitors in vitro and in vivo","volume":"208","author":"Meyer","year":"2013","journal-title":"J. Infect. Dis."},{"key":"B125","doi-asserted-by":"publisher","first-page":"7042","DOI":"10.1016\/S0021-9258(19)50533-6","article-title":"The 90-kDa heat shock protein, HSP90, binds and protects casein kinase II from self-aggregation and enhances its kinase activity","volume":"267","author":"Miyata","year":"1992","journal-title":"J. Biol. Chem."},{"key":"B126","doi-asserted-by":"publisher","first-page":"8203","DOI":"10.1021\/bi800770g","article-title":"Role of the cochaperone Tpr2 in Hsp90 chaperoning","volume":"47","author":"Moffatt","year":"2008","journal-title":"Biochemistry"},{"key":"B127","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1016\/j.bbamcr.2011.07.018","article-title":"Post-translational modifications of Hsp90 and their contributions to chaperone regulation","volume":"1823","author":"Mollapour","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"B128","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1016\/j.molcel.2011.02.011","article-title":"Threonine 22 phosphorylation attenuates Hsp90 interaction with cochaperones and affects its chaperone activity","volume":"41","author":"Mollapour","year":"2011","journal-title":"Mol. Cell"},{"key":"B129","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1021\/acs.jproteome.7b00603","article-title":"Comparative proteomic analysis of lysine acetylation in trypanosomes","volume":"17","author":"Moretti","year":"2018","journal-title":"J. Proteome Res."},{"key":"B130","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/j.pt.2016.04.012","article-title":"Animal african trypanosomiasis: Time to increase focus on clinically relevant parasite and host species","volume":"32","author":"Morrison","year":"2016","journal-title":"Trends Parasitol."},{"key":"B131","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/0166-6851(89)90108-4","article-title":"A transcriptional analysis of the Trypanosoma brucei hsp83 gene cluster","volume":"37","author":"Mottram","year":"1989","journal-title":"Mol. Biochem. Parasitol."},{"key":"B132","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1089\/dna.1996.15.727","article-title":"Identification and characterization of two novel tetratricopeptide repeat-containing genes","volume":"15","author":"Murthy","year":"1996","journal-title":"DNA Cell Biol."},{"key":"B133","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1379\/1466-1268(2003)008<0125:cotcdr>2.0.co;2","article-title":"Comparison of the carboxy-terminal DP-repeat region in the co-chaperones Hop and Hip","volume":"8","author":"Nelson","year":"2003","journal-title":"Cell Stress Chaperones"},{"key":"B134","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1128\/EC.00366-08","article-title":"Identification and specific localization of tyrosine-phosphorylated proteins in trypanosoma brucei","volume":"8","author":"Nett","year":"","journal-title":"Eukaryot. Cell"},{"key":"B135","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1074\/mcp.M800556-MCP200","article-title":"The phosphoproteome of bloodstream form Trypanosoma brucei, causative agent of African sleeping sickness","volume":"8","author":"Nett","year":"","journal-title":"Mol. Cell. Proteomics"},{"key":"B136","doi-asserted-by":"publisher","first-page":"M111010538","DOI":"10.1074\/mcp.M111.010538","article-title":"Independent analysis of the flagellum surface and matrix proteomes provides insight into flagellum signaling in mammalian-infectious trypanosoma brucei","volume":"10","author":"Oberholzer","year":"2011","journal-title":"Mol. Cell. Proteomics"},{"key":"B137","doi-asserted-by":"publisher","first-page":"6896","DOI":"10.1074\/jbc.M206867200","article-title":"Tetratricopeptide repeat motif-mediated hsc70-mSTI1 interaction: Molecular characterization of the critical contacts for successful binding and specificity","volume":"278","author":"Odunuga","year":"2003","journal-title":"J. Biol. Chem."},{"key":"B138","doi-asserted-by":"publisher","first-page":"14279","DOI":"10.1038\/ncomms14279","article-title":"X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3","volume":"8","author":"Olcese","year":"2017","journal-title":"Nat. Commun."},{"key":"B139","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/s12192-009-0160-7","article-title":"The co-chaperone SGT of Leishmania donovani is essential for the parasite\u2019s viability","volume":"15","author":"Ommen","year":"2010","journal-title":"Cell Stress Chaperones"},{"key":"B140","doi-asserted-by":"publisher","first-page":"103735","DOI":"10.1016\/j.jprot.2020.103735","article-title":"Phosphoproteomic analysis of mammalian infective Trypanosoma brucei subjected to heat shock suggests atypical mechanisms for thermotolerance","volume":"219","author":"Ooi","year":"2020","journal-title":"J. Proteomics"},{"key":"B141","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/j.beem.2012.05.003","article-title":"Cellular and molecular mechanisms of mitochondrial function","volume":"26","author":"Osellame","year":"2012","journal-title":"Best. Pract. Res. Clin. Endocrinol. Metab."},{"key":"B142","doi-asserted-by":"publisher","first-page":"37964","DOI":"10.1074\/jbc.M110.155317","article-title":"Heat shock protein 90 as a drug target against Protozoan infections BIOCHEMICAL characterization of hsp90 from plasmodium falciparum and trypanosoma evansi and evaluation of its inhibitor as a candidate drug","volume":"285","author":"Pallavi","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B143","doi-asserted-by":"publisher","first-page":"4829","DOI":"10.1093\/emboj\/17.16.4829","article-title":"ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo","volume":"17","author":"Panaretou","year":"1998","journal-title":"EMBO J."},{"key":"B144","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1002\/pmic.200800477","article-title":"A comprehensive analysis of Trypanosoma brucei mitochondrial proteome","volume":"9","author":"Panigrahi","year":"2009","journal-title":"Proteomics"},{"key":"B145","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1186\/1471-2164-6-127","article-title":"Comparative analysis of the kinomes of three pathogenic trypanosomatids: Leishmania major, Trypanosoma brucei and Trypanosoma cruzi","volume":"6","author":"Parsons","year":"2005","journal-title":"BMC Genomics"},{"key":"B146","doi-asserted-by":"publisher","first-page":"15272","DOI":"10.1038\/ncomms15272","article-title":"Charting organellar importomes by quantitative mass spectrometry","volume":"8","author":"Peikert","year":"2017","journal-title":"Nat. Commun."},{"key":"B147","doi-asserted-by":"publisher","first-page":"e2492","DOI":"10.1371\/JOURNAL.PNTD.0002492","article-title":"Exploring the Trypanosoma brucei Hsp83 potential as a target for structure guided drug design","volume":"7","author":"Pizarro","year":"2013","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B148","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1126\/science.4012301","article-title":"Heat shock genes: Regulatory role for differentiation in parasitic protozoa","volume":"228","author":"Ploeg","year":"1985","journal-title":"Science"},{"key":"B149","doi-asserted-by":"publisher","first-page":"5817","DOI":"10.1038\/sj.onc.1203961","article-title":"TTC4, a novel candidate tumor suppressor gene at 1p31 is often mutated in malignant melanoma of the skin","volume":"19","author":"Poetsch","year":"2000","journal-title":"Oncogene"},{"key":"B150","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1016\/j.cbpa.2010.03.019","article-title":"Discovery and development of Hsp90 inhibitors: A promising pathway for cancer therapy","volume":"14","author":"Porter","year":"2010","journal-title":"Curr. Opin. Chem. Biol."},{"key":"B151","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1016\/j.cellsig.2004.02.004","article-title":"Role of hsp90 and the hsp90-binding immunophilins in signalling protein movement","volume":"16","author":"Pratt","year":"2004","journal-title":"Cell. Signal."},{"key":"B152","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.ijmm.2012.07.004","article-title":"mRNA splicing in trypanosomes","volume":"302","author":"Preu\u00dfer","year":"2012","journal-title":"Int. J. Med. Microbiol."},{"key":"B153","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1093\/emboj\/18.3.754","article-title":"Regulation of Hsp90 ATPase activity by tetratricopeptide repeat (TPR)-domain co-chaperones","volume":"18","author":"Prodromou","year":"1999","journal-title":"EMBO J."},{"key":"B154","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1016\/j.bbamcr.2011.07.020","article-title":"The \u2018active life\u2019 of Hsp90 complexes","volume":"1823","author":"Prodromou","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"B155","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1016\/j.molcel.2017.09.013","article-title":"Picky hsp90\u2014every game with another mate","volume":"67","author":"Radli","year":"2017","journal-title":"Mol. Cell"},{"key":"B156","doi-asserted-by":"publisher","first-page":"1886","DOI":"10.1182\/blood-2008-03-143644","article-title":"HDAC6 inhibition enhances 17-AAG\u2013mediated abrogation of hsp90 chaperone function in human leukemia cells","volume":"112","author":"Rao","year":"2008","journal-title":"Blood"},{"key":"B157","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.2174\/1568026033451934","article-title":"Immunophilin chaperones in steroid receptor signalling","volume":"3","author":"Ratajczak","year":"2003","journal-title":"Curr. Top. Med. Chem."},{"key":"B158","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.2741\/3840","article-title":"Lights and shadows on gene organization and regulation of gene expression in Leishmania","volume":"16","author":"Requena","year":"2011","journal-title":"Front. Biosci."},{"key":"B159","doi-asserted-by":"publisher","first-page":"e301326","DOI":"10.1155\/2015\/301326","article-title":"Molecular chaperones of Leishmania: Central players in many stress-related and -unrelated physiological processes","volume":"2015","author":"Requena","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"B160","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.molcel.2010.01.006","article-title":"Asymmetric activation of the Hsp90 dimer by its cochaperone Aha1","volume":"37","author":"Retzlaff","year":"2010","journal-title":"Mol. Cell"},{"key":"B161","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.molcel.2007.10.007","article-title":"A grp on the Hsp90 mechanism","volume":"28","author":"Richter","year":"2007","journal-title":"Mol. Cell"},{"key":"B162","doi-asserted-by":"publisher","first-page":"71","DOI":"10.3389\/fmolb.2015.00071","article-title":"Structural and functional insights into small, glutamine-rich, tetratricopeptide repeat protein alpha","volume":"2","author":"Roberts","year":"2015","journal-title":"Front. Mol. Biosci."},{"key":"B163","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.tibs.2013.02.003","article-title":"The chaperone Hsp90: Changing partners for demanding clients","volume":"38","author":"R\u00f6hl","year":"2013","journal-title":"Trends biochem. Sci."},{"key":"B164","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.bbamcr.2011.12.003","article-title":"Heat shock protein 90 from neglected protozoan parasites","volume":"1823","author":"Roy","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"B165","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1016\/j.molcel.2017.08.004","article-title":"The plasticity of the Hsp90 Co-chaperone system","volume":"67","author":"Sahasrabudhe","year":"2017","journal-title":"Mol. Cell"},{"key":"B166","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.4161\/cc.19722","article-title":"The expanding proteome of the molecular chaperone HSP90","volume":"11","author":"Samant","year":"2012","journal-title":"Cell Cycle"},{"key":"B167","doi-asserted-by":"publisher","first-page":"30399","DOI":"10.1074\/jbc.M005120200","article-title":"Functional roles of the two domains of phosducin and phosducin-like protein","volume":"275","author":"Savage","year":"2000","journal-title":"J. Biol. Chem."},{"key":"B168","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/S0092-8674(00)80830-2","article-title":"Structure of TPR domain\u2013peptide complexes: Critical elements in the assembly of the hsp70\u2013hsp90 multichaperone machine","volume":"101","author":"Scheufler","year":"2000","journal-title":"Cell"},{"key":"B169","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/nrm3027","article-title":"Common ground for protein translocation: Access control for mitochondria and chloroplasts","volume":"12","author":"Schleiff","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B170","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1590\/s0074-02762011000100012","article-title":"Characterization of TcSTI-1, a homologue of stress-induced protein-1, in Trypanosoma cruzi","volume":"106","author":"Schmidt","year":"2011","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"B171","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/nrm.2017.20","article-title":"The HSP90 chaperone machinery","volume":"18","author":"Schopf","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B172","doi-asserted-by":"publisher","first-page":"e66822","DOI":"10.1371\/journal.pone.0066822","article-title":"Low resolution structural studies indicate that the activator of Hsp90 ATPase 1 (Aha1) of Leishmania braziliensis has an elongated shape which allows its interaction with both N- and M-domains of Hsp90","volume":"8","author":"Seraphim","year":"2013","journal-title":"PLoS One"},{"key":"B173","doi-asserted-by":"publisher","first-page":"e0211507","DOI":"10.1371\/journal.pone.0211507","article-title":"BAP1 expression is prognostic in breast and uveal melanoma but not colon cancer and is highly positively correlated with RBM15B and USP19","volume":"14","author":"Shahriyari","year":"2019","journal-title":"PLoS One"},{"key":"B174","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/nmeth.2413","article-title":"A bright monomeric green fluorescent protein derived from Branchiostoma lanceolatum","volume":"10","author":"Shaner","year":"2013","journal-title":"Nat. Methods"},{"key":"B175","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1074\/mcp.M114.045146","article-title":"Cell surface proteomics provides insight into stage-specific remodeling of the host-parasite interface in trypanosoma brucei","volume":"14","author":"Shimogawa","year":"2015","journal-title":"Mol. Cell. Proteomics"},{"key":"B176","doi-asserted-by":"publisher","first-page":"143","DOI":"10.2174\/092986611794475002","article-title":"Intracellular Protozoan parasites of humans: The role of molecular chaperones in development and pathogenesis","volume":"18","author":"Shonhai","year":"2011","journal-title":"Protein Pept. Lett."},{"key":"B177","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1172\/JCI44855","article-title":"Exploiting the mitochondrial unfolded protein response for cancer therapy in mice and human cells","volume":"121","author":"Siegelin","year":"2011","journal-title":"J. Clin. Invest."},{"key":"B178","doi-asserted-by":"publisher","first-page":"D161","DOI":"10.1093\/nar\/gkp885","article-title":"PROSITE, a protein domain database for functional characterization and annotation","volume":"38","author":"Sigrist","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"B179","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/J.BBAPAP.2012.08.004","article-title":"Structural and functional studies of Leishmania braziliensis Hsp90","volume":"1834","author":"Silva","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"B180","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/1476-072X-9-57","article-title":"The atlas of human african trypanosomiasis: A contribution to global mapping of neglected tropical diseases","volume":"9","author":"Simarro","year":"2010","journal-title":"Int. J. Health Geogr."},{"key":"B181","doi-asserted-by":"publisher","first-page":"362","DOI":"10.4161\/cc.8.3.7531","article-title":"Targeting CDC37: An alternative, kinase-directed strategy for disruption of oncogenic chaperoning","volume":"8","author":"Smith","year":"2009","journal-title":"Cell Cycle"},{"key":"B182","doi-asserted-by":"publisher","first-page":"3574","DOI":"10.1074\/jbc.270.8.3574","article-title":"Identification of a protein with homology to hsp90 that binds the type 1 tumor necrosis factor receptor","volume":"270","author":"Song","year":"1995","journal-title":"J. Biol. Chem."},{"key":"B183","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1007\/s00239-003-2490-x","article-title":"Phylogenetic analysis of eukaryotes using heat-shock protein Hsp90","volume":"57","author":"Stechmann","year":"2003","journal-title":"J. Mol. Evol."},{"key":"B184","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/B978-0-12-374105-9.00254-9","article-title":"Immunophilin ligands","volume-title":"Encyclopedia of movement disorders","author":"Steiner","year":"2010"},{"key":"B185","doi-asserted-by":"publisher","first-page":"283","DOI":"10.4161\/psb.3.5.5576","article-title":"Staying in the fold: The SGT1\/chaperone machinery in maintenance and evolution of leucine-rich repeat proteins","volume":"3","author":"Stuttmann","year":"2008","journal-title":"Plant Signal. Behav."},{"key":"B186","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1006\/geno.1998.5633","article-title":"TTC4, a novel human gene containing the tetratricopeptide repeat and mapping to the region of chromosome 1p31 that is frequently deleted in sporadic breast cancer","volume":"55","author":"Su","year":"1999","journal-title":"Genomics"},{"key":"B187","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/S0014-5793(04)00229-7","article-title":"Hsp90 isoforms: Functions, expression and clinical importance","volume":"562","author":"Subbarao Sreedhar","year":"2004","journal-title":"FEBS Lett."},{"key":"B188","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.1074\/mcp.M113.033357","article-title":"Proteomic analysis of intact flagella of procyclic Trypanosoma brucei cells identifies novel flagellar proteins with unique sub-localization and dynamics","volume":"13","author":"Subota","year":"2014","journal-title":"Mol. Cell. Proteomics"},{"key":"B189","doi-asserted-by":"publisher","first-page":"11553","DOI":"10.1073\/pnas.1833911100","article-title":"A candidate gene for developmental dyslexia encodes a nuclear tetratricopeptide repeat domain protein dynamically regulated in brain","volume":"100","author":"Taipale","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B190","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/j.cell.2012.06.047","article-title":"Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition","volume":"150","author":"Taipale","year":"2012","journal-title":"Cell"},{"key":"B191","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.cell.2014.05.039","article-title":"A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways","volume":"158","author":"Taipale","year":"2014","journal-title":"Cell"},{"key":"B192","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1017\/S0031182014000778","article-title":"Chaperoning parasitism: The importance of molecular chaperones in pathogen virulence","volume":"141","author":"Tatu","year":"2014","journal-title":"Parasitology"},{"key":"B193","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/nrc2887","article-title":"Targeting the dynamic HSP90 complex in cancer","volume":"10","author":"Trepel","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"B194","doi-asserted-by":"publisher","first-page":"e36619","DOI":"10.1371\/journal.pone.0036619","article-title":"Comparative SILAC proteomic analysis of Trypanosoma brucei bloodstream and procyclic lifecycle stages","volume":"7","author":"Urbaniak","year":"2012","journal-title":"PLoS ONE"},{"key":"B195","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.1021\/pr400086y","article-title":"Global quantitative SILAC phosphoproteomics reveals differential phosphorylation is widespread between the procyclic and bloodstream form lifecycle stages of Trypanosoma brucei","volume":"12","author":"Urbaniak","year":"2013","journal-title":"J. Proteome Res."},{"key":"B196","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1007\/978-94-007-7305-9_5","article-title":"The heat shock proteins of Trypanosoma cruzi","volume":"74","author":"Urm\u00e9nyi","year":"2014","journal-title":"Subcell. Biochem."},{"key":"B197","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/0014-4894(66)90015-4","article-title":"The trypanosomatid parasites of insects and arachnids","volume":"18","author":"Wallace","year":"1966","journal-title":"Exp. Parasitol."},{"key":"B198","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1093\/BIOINFORMATICS\/BTP033","article-title":"Jalview version 2\u2014A multiple sequence alignment editor and analysis workbench","volume":"25","author":"Waterhouse","year":"2009","journal-title":"Bioinformatics"},{"key":"B199","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/s0166-6851(97)00115-1","article-title":"Molecular characterization of the heat-inducible LmSTI1 protein of Leishmania major","volume":"89","author":"Webb","year":"1997","journal-title":"Mol. Biochem. Parasitol."},{"key":"B200","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1038\/nrc1716","article-title":"HSP90 and the chaperoning of cancer","volume":"5","author":"Whitesell","year":"2005","journal-title":"Nat. Rev. Cancer"},{"key":"B201","volume-title":"WHO interim guidelines for the treatment of gambiense human African trypanosomiasis","author":"WHO","year":"2019"},{"key":"B202","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s004300100074","article-title":"The heat shock protein 90 of Leishmania donovani","volume":"190","author":"Wiesgigl","year":"2001","journal-title":"Med. Microbiol. Immunol."},{"key":"B203","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.1016\/j.cellsig.2007.06.013","article-title":"Function of phosducin-like proteins in G protein signaling and chaperone-assisted protein folding","volume":"19","author":"Willardson","year":"2007","journal-title":"Cell. Signal."},{"key":"B204","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.febslet.2004.12.005","article-title":"Mammalian CHORD-containing protein 1 is a novel heat shock protein 90-interacting protein","volume":"579","author":"Wu","year":"2005","journal-title":"FEBS Lett."},{"key":"B205","doi-asserted-by":"publisher","first-page":"4728","DOI":"10.1242\/jcs.155648","article-title":"SGTA regulates the cytosolic quality control of hydrophobic substrates","volume":"127","author":"Wunderley","year":"2014","journal-title":"J. Cell Sci."},{"key":"B206","doi-asserted-by":"publisher","first-page":"4833","DOI":"10.1158\/0008-5472.CAN-08-0644","article-title":"Role of acetylation and extracellular location of heat shock protein 90alpha in tumor cell invasion","volume":"68","author":"Yang","year":"2008","journal-title":"Cancer Res."},{"key":"B207","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0166-6851(03)00211-1","article-title":"The major surface protease (MSP or GP63) of Leishmania sp. Biosynthesis, regulation of expression, and function","volume":"132","author":"Yao","year":"2003","journal-title":"Mol. Biochem. Parasitol."},{"key":"B208","doi-asserted-by":"publisher","first-page":"e729","DOI":"10.1371\/journal.pntd.0000729","article-title":"Cyclosporin A treatment of Leishmania donovani reveals stage-specific functions of cyclophilins in parasite proliferation and viability","volume":"4","author":"Yau","year":"2010","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B209","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1111\/mmi.12639","article-title":"The L eishmania donovani chaperone cyclophilin 40 is essential for intracellular infection independent of its stage-specific phosphorylation status: LdCyP40 null mutant analysis","volume":"93","author":"Yau","year":"2014","journal-title":"Mol. Microbiol."},{"key":"B210","doi-asserted-by":"publisher","first-page":"5930","DOI":"10.1093\/emboj\/19.21.5930","article-title":"Polypeptide release by Hsp90 involves ATP hydrolysis and is enhanced by the co-chaperone p23","volume":"19","author":"Young","year":"2000","journal-title":"EMBO J."},{"key":"B211","doi-asserted-by":"publisher","first-page":"101074","DOI":"10.1016\/j.isci.2020.101074","article-title":"Landscapes of protein posttranslational modifications of african trypanosoma parasites","volume":"23","author":"Zhang","year":"2020","journal-title":"iScience"},{"key":"B212","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1083\/jcb.200709061","article-title":"Molecular chaperone Hsp90 stabilizes Pih1\/Nop17 to maintain R2TP complex activity that regulates snoRNA accumulation","volume":"180","author":"Zhao","year":"2008","journal-title":"J. Cell Biol."},{"key":"B213","doi-asserted-by":"publisher","first-page":"30316","DOI":"10.1074\/jbc.M402664200","article-title":"NCB5OR is a novel soluble NAD(P)H reductase localized in the endoplasmic reticulum","volume":"279","author":"Zhu","year":"2004","journal-title":"J. Biol. Chem."},{"key":"B214","doi-asserted-by":"publisher","first-page":"14742","DOI":"10.1073\/pnas.96.26.14742","article-title":"Identification of a cytochrome b -type NAD(P)H oxidoreductase ubiquitously expressed in human cells","volume":"96","author":"Zhu","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B215","doi-asserted-by":"publisher","first-page":"5930","DOI":"10.3390\/ijms20235930","article-title":"Small molecule inhibitors targeting the heat shock protein system of human obligate Protozoan parasites","volume":"20","author":"Zininga","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B216","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1002\/bip.21292","article-title":"Hsp90 and co-chaperones twist the functions of diverse client proteins","volume":"93","author":"Zuehlke","year":"2010","journal-title":"Biopolymers"}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2022.947078\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T11:29:21Z","timestamp":1663932561000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2022.947078\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,23]]},"references-count":216,"alternative-id":["10.3389\/fmolb.2022.947078"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2022.947078","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,23]]},"article-number":"947078"}}