{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:56:55Z","timestamp":1788947815662,"version":"build-2803163510"},"reference-count":77,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T00:00:00Z","timestamp":1673827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deputyship for Research and Innovation, Ministry of Education, Saudi Arabia","award":["IF-2020-NBU-243"],"award-info":[{"award-number":["IF-2020-NBU-243"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Leishmania tropica is a tropical parasite causing cutaneous leishmaniasis (CL) in humans. Leishmaniasis is a serious public health threat, affecting an estimated 350 million people in 98 countries. The global rise in antileishmanial drug resistance has triggered the need to explore novel therapeutic strategies against this parasite. In the present study, we utilized the recently available multidrug resistant L. tropica strain proteome data repository to identify alternative therapeutic drug targets based on comparative subtractive proteomic and druggability analyses. Additionally, small drug-like compounds were scanned against novel targets based on virtual screening and ADME profiling. The analysis unveiled 496 essential cellular proteins of L. tropica that were nonhomologous to the human proteome set. The druggability analyses prioritized nine parasite-specific druggable proteins essential for the parasite\u2019s basic cellular survival, growth, and virulence. These prioritized proteins were identified to have appropriate binding pockets to anchor small drug-like compounds. Among these, UDPase and PCNA were prioritized as the top-ranked druggable proteins. The pharmacophore-based virtual screening and ADME profiling predicted MolPort-000-730-162 and MolPort-020-232-354 as the top hit drug-like compounds from the Pharmit resource to inhibit L. tropica UDPase and PCNA, respectively. The alternative drug targets and drug-like molecules predicted in the current study lay the groundwork for developing novel antileishmanial therapies.<\/jats:p>","DOI":"10.3390\/microorganisms11010228","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T02:10:32Z","timestamp":1673921432000},"page":"228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Comparative Proteomics and Genome-Wide Druggability Analyses Prioritized Promising Therapeutic Targets against Drug-Resistant Leishmania tropica"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4115-4984","authenticated-orcid":false,"given":"Sara","family":"Aiman","sequence":"first","affiliation":[{"name":"Faculty of Environmental and Life Sciences, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5456-5769","authenticated-orcid":false,"given":"A. Khuzaim","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Medical Laboratory Technology, Faculty of Applied Medical Sciences, Northern Border University, Arar 91431, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5331-7816","authenticated-orcid":false,"given":"Fawad","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Abida","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6064-1040","authenticated-orcid":false,"given":"Mohd.","family":"Imran","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3585-0828","authenticated-orcid":false,"given":"Mehnaz","family":"Kamal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Usman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamdy Khamees","family":"Thabet","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Arts and Science, Northern Border University, Rafha 91911, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhua","family":"Li","sequence":"additional","affiliation":[{"name":"Faculty of Environmental and Life Sciences, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1444-4249","authenticated-orcid":false,"given":"Asifullah","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.apar.2018.11.001","article-title":"Leishmania tropica: What we know from its experimental models","volume":"104","author":"Rostamian","year":"2019","journal-title":"Adv. Parasitol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/qjmed\/hct116","article-title":"Leishmaniasis: Clinical syndromes and treatment","volume":"107","author":"McGwire","year":"2014","journal-title":"QJM"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Azim, M., Khan, S.A., Ullah, S., Ullah, S., and Anjum, S.I. (2021). Therapeutic advances in the topical treatment of cutaneous leishmaniasis: A review. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009099"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1017\/S0031182020002413","article-title":"Epidemiological and pathological characteristics of Cutaneous Leishmaniasis from Baluchistan Province of Pakistan","volume":"148","author":"Khan","year":"2021","journal-title":"Parasitology"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Salloum, T., Moussa, R., Rahy, R., Al Deek, J., Khalifeh, I., El Hajj, R., Hall, N., Hirt, R.P., and Tokajian, S. (2020). Expanded genome-wide comparisons give novel insights into population structure and genetic heterogeneity of Leishmania tropica complex. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008684"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s40475-021-00232-7","article-title":"A Review of Leishmaniasis: Current Knowledge and Future Directions","volume":"8","author":"Mann","year":"2021","journal-title":"Curr. Trop. Med. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1136\/bmj.308.6924.307","article-title":"Clinicoepidemiological study of drug resistance in Indian kala-azar","volume":"308","author":"Sundar","year":"1994","journal-title":"BMJ"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s40257-015-0114-z","article-title":"Cutaneous Leishmaniasis: Recent Developments in Diagnosis and Management","volume":"16","author":"Reedijk","year":"2015","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s12551-013-0134-y","article-title":"Antimony transport mechanisms in resistant leishmania parasites","volume":"6","author":"Reis","year":"2014","journal-title":"Biophys. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Perez-Franco, J.E., Cruz-Barrera, M.L., Robayo, M.L., Lopez, M.C., Daza, C.D., Bedoya, A., Mari\u00f1o, M.L., Saavedra, C.H., and Echeverry, M.C. (2016). Clinical and parasitological features of patients with American cutaneous leishmaniasis that did not respond to treatment with meglumine antimoniate. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004739"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Deep, D.K., Singh, R., Bhandari, V., Verma, A., Sharma, V., Wajid, S., Sundar, S., Ramesh, V., Dujardin, J.C., and Salotra, P. (2017). Increased miltefosine tolerance in clinical isolates of Leishmania donovani is associated with reduced drug accumulation, increased infectivity and resistance to oxidative stress. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005641"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lin, X., Li, X., and Lin, X. (2020). A Review on Applications of Computational Methods in Drug Screening and Design. Molecules, 25.","DOI":"10.3390\/molecules25061375"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"104293","DOI":"10.1016\/j.micpath.2020.104293","article-title":"Identification and qualitative characterization of new therapeutic targets in Stenotrophomonas maltophilia through in silico proteome exploration","volume":"149","author":"Chakrabarty","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/ddr.21669","article-title":"A comprehensive review of computational techniques for the prediction of drug side effects","volume":"81","author":"Sachdev","year":"2020","journal-title":"Drug Dev. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e0054521","DOI":"10.1128\/MRA.00545-21","article-title":"Genome Assemblies across the Diverse Evolutionary Spectrum of Leishmania Protozoan Parasites","volume":"10","author":"Warren","year":"2021","journal-title":"Microbiol. Resour. Announc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1093\/bioinformatics\/btq003","article-title":"CD-HIT Suite: A web server for clustering and comparing biological sequences","volume":"26","author":"Huang","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"D574","DOI":"10.1093\/nar\/gkt1131","article-title":"DEG 10, an update of the database of essential genes that includes both protein-coding genes and noncoding genomic elements","volume":"42","author":"Luo","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"W5","DOI":"10.1093\/nar\/gkn201","article-title":"NCBI BLAST: A better web interface","volume":"36","author":"Johnson","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"D23","DOI":"10.1093\/nar\/gky1069","article-title":"Database resources of the National Center for Biotechnology Information","volume":"47","author":"Sayers","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ygeno.2016.11.005","article-title":"TiD: Standalone software for mining putative drug targets from bacterial proteome","volume":"109","author":"Gupta","year":"2017","journal-title":"Genomics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"D901","DOI":"10.1093\/nar\/gkm958","article-title":"DrugBank: A knowledgebase for drugs, drug actions and drug targets","volume":"36","author":"Wishart","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: Homology modelling of protein structures and complexes","volume":"46","author":"Waterhouse","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/prot.10286","article-title":"Structure validation by Calpha geometry: Phi,psi and Cbeta deviation","volume":"50","author":"Lovell","year":"2003","journal-title":"Proteins"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/nrd2684","article-title":"Genomic-scale prioritization of drug targets: The TDR Targets database","volume":"7","author":"Aslett","year":"2008","journal-title":"Nat. Rev. Drug Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1093\/bioinformatics\/btq249","article-title":"PSORTb 3.0: Improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all prokaryotes","volume":"26","author":"Yu","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Yu, C.S., Cheng, C.W., Su, W.C., Chang, K.C., Huang, S.W., Hwang, J.K., and Lu, C.H. (2014). CELLO2GO: A Web Server for Protein subCELlular LOcalization Prediction with Functional Gene Ontology Annotation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099368"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1021\/ci5006004","article-title":"PockDrug: A Model for Predicting Pocket Druggability That Overcomes Pocket Estimation Uncertainties","volume":"55","author":"Borrel","year":"2015","journal-title":"J. Chem. Inf. Model."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"W442","DOI":"10.1093\/nar\/gkw287","article-title":"Pharmit: Interactive exploration of chemical space","volume":"44","author":"Sunseri","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/s41401-019-0228-6","article-title":"CB-Dock: A web server for cavity detection-guided protein\u2013ligand blind docking","volume":"41","author":"Liu","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s13071-020-3999-1","article-title":"Genetic validation of Leishmania genes essential for amastigote survival in vivo using N-myristoyltransferase as a model","volume":"13","author":"Paape","year":"2020","journal-title":"Parasit. Vectors"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1007\/s13258-019-00857-z","article-title":"Proteome-wide subtractive approach to prioritize a hypothetical protein of XDR-Mycobacterium tuberculosis as potential drug target","volume":"41","author":"Uddin","year":"2019","journal-title":"Genes Genom."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Fatoba, A.J., Okpeku, M., and Adeleke, M.A. (2021). Subtractive Genomics Approach for Identification of Novel Therapeutic Drug Targets in Mycoplasma genitalium. Pathogens, 10.","DOI":"10.3390\/pathogens10080921"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1089\/mdr.2016.0259","article-title":"Genome-Wide Identification of Potential Drug Target in Enterobacteriaceae Family: A Homology-Based Method","volume":"24","author":"Hadizadeh","year":"2018","journal-title":"Microb. Drug Resist."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1186\/s12936-021-03865-1","article-title":"Analysing the essential proteins set of Plasmodium falciparum PF3D7 for novel drug targets identification against malaria","volume":"20","author":"Ali","year":"2021","journal-title":"Malar. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1742-4682-10-22","article-title":"Homology modeling and virtual screening approaches to identify potent inhibitors of VEB-1 \u03b2-lactamase","volume":"10","author":"Messaoudi","year":"2013","journal-title":"Theor. Biol. Med. Model."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1021\/acscatal.7b03714","article-title":"Decoding Allosteric Networks in Biocatalysts: Rational Approach to Therapies and Biotechnologies","volume":"8","author":"Cramer","year":"2018","journal-title":"ACS Catal."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/90761","article-title":"ADMET\u2014Turning chemicals into drugs","volume":"19","author":"Hodgson","year":"2001","journal-title":"Nat. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"46","author":"Lipinski","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"105004","DOI":"10.1016\/j.meegid.2021.105004","article-title":"Therapeutic target identification via differential genome analysis of antibiotic resistant Shigella sonnei and inhibitor evaluation against a selected drug target","volume":"94","author":"Basharat","year":"2021","journal-title":"Infect. Genet. Evol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","article-title":"Leishmaniasis","volume":"392","author":"Burza","year":"2018","journal-title":"Lancet"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.mib.2013.07.010","article-title":"Protein interaction networks as starting points to identify novel antimicrobial drug targets","volume":"16","author":"Zoraghi","year":"2013","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"He, X., and Zhang, J. (2006). Why Do Hubs Tend to Be Essential in Protein Networks?. PLoS Genet., 2.","DOI":"10.1371\/journal.pgen.0020088"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"16314","DOI":"10.1074\/jbc.M600076200","article-title":"Molecular cloning of the Leishmania major UDP-glucose pyrophosphorylase, functional characterization, and ligand binding analyses using NMR spectroscopy","volume":"281","author":"Lamerz","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0166-6851(03)00079-3","article-title":"Improvements in transfection efficiency and tests of RNA interference (RNAi) approaches in the protozoan parasite Leishmania","volume":"128","author":"Robinson","year":"2003","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1128\/EC.00175-07","article-title":"Sugar nucleotide pools of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major","volume":"6","author":"Turnock","year":"2007","journal-title":"Eukaryot. Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"13003","DOI":"10.1074\/jbc.M609984200","article-title":"Open and Closed Structures of the UDP-glucose Pyrophosphorylase from Leishmania major*","volume":"282","author":"Steiner","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"649","DOI":"10.2174\/1566524043360069","article-title":"Surface determinants of Leishmania parasites and their role in infectivity in the mammalian host","volume":"4","author":"Naderer","year":"2004","journal-title":"Curr. Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1073\/pnas.97.1.406","article-title":"The role of phosphoglycans in Leishmania-sand fly interactions","volume":"97","author":"Sacks","year":"2000","journal-title":"Prol. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Damerow, S., Hoppe, C., Bandini, G., Zarnovican, P., Buettner, F.R., L\u00fcder, C.G.K., Ferguson, M.A.J., and Routier, F.H. (2015). Depletion of UDP-Glucose and UDP-Galactose Using a Degron System Leads to Growth Cessation of Leishmania major. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0004205"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Prakash, O., F\u00fchring, J., Post, J., Shepherd, S.M., Eadsforth, T.C., Gray, D., Fedorov, R., and Routier, F.H. (2019). Identification of Leishmania major UDP-Sugar Pyrophosphorylase Inhibitors Using Biosensor-Based Small Molecule Fragment Library Screening. Molecules, 24.","DOI":"10.3390\/molecules24050996"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/sj.onc.1200886","article-title":"PCNA: Structure, functions and interactions","volume":"14","author":"Kelman","year":"1997","journal-title":"Oncogene"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1093\/aob\/mcq243","article-title":"Proliferating cell nuclear antigen (PCNA): A key factor in DNA replication and cell cycle regulation","volume":"107","author":"Strzalka","year":"2011","journal-title":"Ann. Bot."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3748","DOI":"10.1099\/mic.0.033217-0","article-title":"The distribution pattern of proliferating cell nuclear antigen in the nuclei of Leishmania donovani","volume":"155","author":"Kumar","year":"2009","journal-title":"Microbiology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1128\/AAC.01847-13","article-title":"Characterization of the proliferating cell nuclear antigen of Leishmania donovani clinical isolates and its association with antimony resistance","volume":"58","author":"Tandon","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1099\/jmm.0.46841-0","article-title":"Molecular mechanisms of antimony resistance in Leishmania","volume":"56","author":"Ashutosh","year":"2007","journal-title":"J. Med. Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1074\/jbc.M209395200","article-title":"3-Mercaptopyruvate sulfurtransferase of Leishmania contains an unusual C-terminal extension and is involved in thioredoxin and antioxidant metabolism","volume":"278","author":"Williams","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"33883","DOI":"10.1074\/jbc.M003671200","article-title":"Inducible resistance to oxidant stress in the protozoan Leishmania chagasi","volume":"275","author":"Miller","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S1357-2725(99)00035-7","article-title":"Rhodanese as a thioredoxin oxidase","volume":"32","author":"Nandi","year":"2000","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"a011536","DOI":"10.1101\/cshperspect.a011536","article-title":"The structure and function of the eukaryotic ribosome","volume":"4","author":"Wilson","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"13223","DOI":"10.1038\/ncomms13223","article-title":"Structures and stabilization of kinetoplastid-specific split rRNAs revealed by comparing leishmanial and human ribosomes","volume":"7","author":"Zhang","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/nchembio.1158","article-title":"Essential nontranslational functions of tRNA synthetases","volume":"9","author":"Guo","year":"2013","journal-title":"Nat. Chem. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"17754","DOI":"10.1074\/jbc.M116.727107","article-title":"Twin Attributes of Tyrosyl-tRNA Synthetase of Leishmania donovani: A housekeeping protein translation enzyme and a mimic of host chemokine","volume":"291","author":"Anand","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"22648","DOI":"10.1074\/jbc.M114.573972","article-title":"Mechanistic study of Uba5 enzyme and the Ufm1 conjugation pathway","volume":"289","author":"Gavin","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"8399","DOI":"10.1038\/s41598-018-26532-z","article-title":"Ubiquitin Proteasome pathway proteins as potential drug targets in parasite Trypanosoma cruzi","volume":"8","author":"Gupta","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"630888","DOI":"10.3389\/fchem.2020.630888","article-title":"Ubiquitination and the Proteasome as Drug Targets in Trypanosomatid Diseases","volume":"8","author":"Bijlmakers","year":"2021","journal-title":"Front. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/S0014-5793(03)00603-3","article-title":"PTP1B: From the sidelines to the front lines!","volume":"546","author":"Tonks","year":"2003","journal-title":"FEBS Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6272","DOI":"10.1128\/IAI.00853-05","article-title":"Role of host protein tyrosine phosphatase SHP-1 in Leishmania donovani-induced inhibition of nitric oxide production","volume":"74","author":"Forget","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e00084-17","DOI":"10.1128\/IAI.00084-17","article-title":"Characterization of the Protein Tyrosine Phosphatase LmPRL-1 Secreted by Leishmania major via the Exosome Pathway","volume":"85","author":"Leitherer","year":"2017","journal-title":"Infect. Immun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"36257","DOI":"10.1074\/jbc.M606256200","article-title":"Identification and Characterization of a Protein-tyrosine Phosphatase in Leishmania","volume":"281","author":"Nascimento","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1091\/mbc.12.1.221","article-title":"Multiple roles of Arf1 GTPase in the yeast exocytic and endocytic pathways","volume":"12","author":"Yahara","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Sahin, A., Espiau, B., Tetaud, E., Cuvillier, A., Lartigue, L., Ambit, A., Robinson, D.R., and Merlin, G. (2008). The leishmania ARL-1 and Golgi traffic. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001620"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1111\/j.1600-0854.2004.00229.x","article-title":"LdARF1 in trafficking and structural maintenance of the trans-Golgi cisternal network in the protozoan pathogen Leishmania donovani","volume":"5","author":"Gerald","year":"2004","journal-title":"Traffic"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1242\/jcs.01624","article-title":"Functional analysis of TbARL1, an N-myristoylated Golgi protein essential for viability in bloodstream trypanosomes","volume":"118","author":"Price","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.molbiopara.2010.08.002","article-title":"Crystal structure of Leishmania major ADP-ribosylation factor-like 1 and a classification of related GTPase family members in this Kinetoplastid","volume":"174","author":"Fleming","year":"2010","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1016\/j.bbamcr.2016.03.015","article-title":"The transport mechanism of the mitochondrial ADP\/ATP carrier","volume":"1863","author":"Kunji","year":"2016","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e1004875","DOI":"10.1371\/journal.ppat.1004875","article-title":"An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei","volume":"11","author":"Niemann","year":"2015","journal-title":"PLoS Pathog."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/1\/228\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:07:39Z","timestamp":1760119659000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/1\/228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,16]]},"references-count":77,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["microorganisms11010228"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms11010228","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,16]]}}}