{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:42:19Z","timestamp":1787730139750,"version":"build-2784847793"},"reference-count":58,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI148214"],"award-info":[{"award-number":["R01AI148214"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15GM125065"],"award-info":[{"award-number":["R15GM125065"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM103408"],"award-info":[{"award-number":["P20GM103408"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM109095"],"award-info":[{"award-number":["P20GM109095"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R25GM123927."],"award-info":[{"award-number":["R25GM123927."]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The first line therapy for Lyme disease is treatment with doxycycline, amoxicillin, or cefuroxime. In endemic regions, the persistence of symptoms in many patients after completion of antibiotic treatment remains a major healthcare concern. The causative agent of Lyme disease is a spirochete, Borrelia burgdorferi, an extreme auxotroph that cannot exist under free-living conditions and depends upon the tick vector and mammalian hosts to fulfill its nutritional needs. Despite lacking all major biosynthetic pathways, B. burgdorferi uniquely possesses three homologous and functional methylthioadenosine\/S-adenosylhomocysteine nucleosidases (MTANs: Bgp, MtnN, and Pfs) involved in methionine and purine salvage, underscoring the critical role these enzymes play in the life cycle of the spirochete. At least one MTAN, Bgp, is exceptional in its presence on the surface of Lyme spirochetes and its dual functionality in nutrient salvage and glycosaminoglycan binding involved in host-cell adherence. Thus, MTANs offer highly promising targets for discovery of new antimicrobials. Here we report on our studies to evaluate five nucleoside analogs for MTAN inhibitory activity, and cytotoxic or cytostatic effects on a bioluminescently engineered strain of B. burgdorferi. All five compounds were either alternate substrates and\/or inhibitors of MTAN activity, and reduced B. burgdorferi growth. Two inhibitors: 5\u2032-deoxy-5\u2032-iodoadenosine (IADO) and 5\u2032-deoxy-5\u2032-ethyl-immucillin A (dEt-ImmA) showed bactericidal activity. Thus, these inhibitors exhibit high promise and form the foundation for development of novel and effective antimicrobials to treat Lyme disease.<\/jats:p>","DOI":"10.3390\/pathogens9090678","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T21:13:42Z","timestamp":1597958022000},"page":"678","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Evaluation of Nucleoside Analogs as Antimicrobials Targeting Unique Enzymes in Borrelia burgdorferi"],"prefix":"10.3390","volume":"9","author":[{"given":"Monideep","family":"Chakraborti","sequence":"first","affiliation":[{"name":"Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Schlachter","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"},{"name":"Department of Biology, Saint Elizabeth University, 2 Convent Road, Henderson Hall Room 112C, Morristown, NJ 07960, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shekerah","family":"Primus","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Boise State University, Boise, ID 83725, USA"},{"name":"Bridges to Baccalaureate Program, Boise State University, Boise, ID 83725, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6375-4147","authenticated-orcid":false,"given":"Brandi","family":"Sweet","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Boise State University, Boise, ID 83725, USA"},{"name":"Bridges to Baccalaureate Program, Boise State University, Boise, ID 83725, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7622-7725","authenticated-orcid":false,"given":"Zoey","family":"Carr","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Boise State University, Boise, ID 83725, USA"},{"name":"Bridges to Baccalaureate Program, Boise State University, Boise, ID 83725, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3959-2499","authenticated-orcid":false,"given":"Kenneth A.","family":"Cornell","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Boise State University, Boise, ID 83725, USA"},{"name":"Biomolecular Research Center; Boise State University, Boise, ID 83725, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0592-0693","authenticated-orcid":false,"given":"Nikhat","family":"Parveen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.3201\/eid2207.151694","article-title":"Current Guidelines, Common Clinical Pitfalls, and Future Directions for Laboratory Diagnosis of Lyme Disease, United States","volume":"22","author":"Moore","year":"2016","journal-title":"Emerg. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1086\/506936","article-title":"Comparison of findings for patients with Borrelia garinii and Borrelia afzelii isolated from cerebrospinal fluid","volume":"43","author":"Strle","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJM200107123450207","article-title":"Lyme disease","volume":"345","author":"Steere","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1086\/508667","article-title":"The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: Clinical practice guidelines by the Infectious Diseases Society of America","volume":"43","author":"Wormser","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","unstructured":"Hu, L.T. (2020, August 19). Patient education: Lyme disease symptoms and diagnosis (Beyond the Basics). Available online: https:\/\/www.uptodate.com\/contents\/lyme-disease-symptoms-and-diagnosis-beyond-the-basics."},{"key":"ref_6","unstructured":"Centers for Disease Control and Prevention (2019, December 17). Lyme disease treatment, Available online: https:\/\/www.cdc.gov\/lyme\/treatment\/index.html."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1056\/NEJM199707313370501","article-title":"Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease","volume":"337","author":"Dattwyler","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s00508-005-0361-8","article-title":"A comparison of two treatment regimens of ceftriaxone in late Lyme disease","volume":"117","author":"Dattwyler","year":"2005","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_9","unstructured":"Hu, L.T. (2020, July 15). Treatment of Lyme disease. Available online: https:\/\/www.uptodate.com\/contents\/treatment-of-lyme-disease."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1086\/314860","article-title":"Successful treatment of Lyme encephalopathy with intravenous ceftriaxone","volume":"180","author":"Logigian","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1365-2958.2010.07455.x","article-title":"Methylthioadenosine\/S-adenosylhomocysteine nucleosidase, a critical enzyme for bacterial metabolism","volume":"79","author":"Parveen","year":"2011","journal-title":"Mol. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1006\/bbrc.1996.1723","article-title":"Characterization of recombinant Escherichia coli 5\u2019-methylthioadenosine\/S-adenosylhomocysteine nucleosidase: Analysis of enzymatic activity and substrate specificity","volume":"228","author":"Cornell","year":"1996","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.chembiol.2005.04.012","article-title":"A nucleosidase required for in vivo function of the S-adenosyl-L-methionine radical enzyme, biotin synthase","volume":"12","author":"Cronan","year":"2005","journal-title":"Chem. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5240","DOI":"10.1074\/jbc.M109.056606","article-title":"Catalytic activity of the anaerobic tyrosine lyase required for thiamine biosynthesis in Escherichia coli","volume":"285","author":"Challand","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/j.febslet.2009.03.044","article-title":"Product inhibition in the radical S-adenosylmethionine family","volume":"583","author":"Challand","year":"2009","journal-title":"FEBS Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"19392","DOI":"10.1074\/jbc.M111.229781","article-title":"5\u2019-methylthioadenosine nucleosidase is implicated in playing a key role in a modified futalosine pathway for menaquinone biosynthesis in Campylobacter jejuni","volume":"286","author":"Li","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1038\/s41429-018-0087-2","article-title":"Aplasmomycin and boromycin are specific inhibitors of the futalosine pathway","volume":"71","author":"Shimizu","year":"2018","journal-title":"J. Antibiot. (Tokyo)"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"129455","DOI":"10.1016\/j.bbagen.2019.129455","article-title":"Characterization of 5\u2019-methylthioadenosine\/S-adenosylhomocysteine nucleosidases from Borrelia burgdorferi: Antibiotic targets for Lyme disease","volume":"1864","author":"Cornell","year":"2020","journal-title":"Biochim. Biophys. Acta. Gen. Subj."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nchembio.153","article-title":"Transition state analogs of 5\u2019-methylthioadenosine nucleosidase disrupt quorum sensing","volume":"5","author":"Gutierrez","year":"2009","journal-title":"Nat. Chem. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1046\/j.1365-2958.2000.01792.x","article-title":"Identification of a candidate glycosaminoglycan-binding adhesin of the Lyme disease spirochete Borrelia burgdorferi","volume":"35","author":"Parveen","year":"2000","journal-title":"Mol. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1093\/jac\/dkp129","article-title":"Assessment of methylthioadenosine\/S-adenosylhomocysteine nucleosidases of Borrelia burgdorferi as targets for novel antimicrobials using a novel high-throughput method","volume":"63","author":"Cornell","year":"2009","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1111\/j.1365-2958.2009.06621.x","article-title":"Rrp1, a cyclic-di-GMP-producing response regulator, is an important regulator of Borrelia burgdorferi core cellular functions","volume":"71","author":"Rogers","year":"2009","journal-title":"Mol. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mongodin, E.F., Casjens, S.R., Bruno, J.F., Xu, Y., Drabek, E.F., Riley, D.R., Cantarel, B.L., Pagan, P.E., Hernandez, Y.A., and Vargas, L.C. (2013). Inter- and intra-specific pan-genomes of Borrelia burgdorferi sensu lato: Genome stability and adaptive radiation. BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-693"},{"key":"ref_24","unstructured":"Parveen, N., and Leong, J.M. (2006). Genetic Analysis of Attachment of Borrelia Burgdorferi to Host Cells and Extracellular Matrix, IOS Press."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Schlachter, S., Seshu, J., Lin, T., Norris, S., and Parveen, N. (2018). The Borrelia burgdorferi Glycosaminoglycan Binding Protein Bgp in the B31 Strain Is Not Essential for Infectivity despite Facilitating Adherence and Tissue Colonization. Infect. Immun., 86.","DOI":"10.1128\/IAI.00667-17"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4151","DOI":"10.1016\/S0021-9258(17)40245-6","article-title":"Charges of nicotinamide adenine nucleotides and adenylate energy charge as regulatory parameters of the metabolism in Escherichia coli","volume":"252","author":"Andersen","year":"1977","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0065-2911(08)60318-5","article-title":"Adenine nucleotide concentrations and turnover rates. Their correlation with biological activity in bacteria and yeast","volume":"15","author":"Chapman","year":"1977","journal-title":"Adv. Microb. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/nri.2016.4","article-title":"Purinergic regulation of the immune system","volume":"16","author":"Cekic","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/nchembio.740","article-title":"Microbial environments confound antibiotic efficacy","volume":"8","author":"Lee","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Cantoni, G.L. (1986). The Centrality of S-Adenosylhomocysteinase in the Regulation of the Biological Utilization of S-Adenosylmethionine., Humana Press.","DOI":"10.1007\/978-1-4612-5012-8_19"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3450","DOI":"10.1128\/JB.184.13.3450-3456.2002","article-title":"pfs-dependent regulation of autoinducer 2 production in Salmonella enterica serovar Typhimurium","volume":"184","author":"Beeston","year":"2002","journal-title":"J. Bacteriol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ab.2010.04.021","article-title":"Quantitative liquid chromatography-tandem mass spectrometry profiling of activated methyl cycle metabolites involved in LuxS-dependent quorum sensing in Escherichia coli","volume":"403","author":"Halliday","year":"2010","journal-title":"Anal. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/nchembio.117","article-title":"Targeted polypharmacology: Discovery of dual inhibitors of tyrosine and phosphoinositide kinases","volume":"4","author":"Apsel","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ijmm.2013.03.004","article-title":"Methylthioadenosine\/S-adenosylhomocysteine nucleosidase (Pfs) of Staphylococcus aureus is essential for the virulence independent of LuxS\/AI-2 system","volume":"303","author":"Bao","year":"2013","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1089\/adt.2006.053","article-title":"Bioluminescent assays for high-throughput screening","volume":"5","author":"Fan","year":"2007","journal-title":"Assay Drug Dev. Technol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"688","DOI":"10.4103\/0971-5916.90997","article-title":"Non invasive real-time monitoring of bacterial infection & therapeutic effect of anti-microbials in five mouse models","volume":"134","author":"Barman","year":"2011","journal-title":"Indian J. Med. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2806","DOI":"10.1128\/AAC.00400-10","article-title":"Rapid assessment of antibacterial activity against Mycobacterium ulcerans by using recombinant luminescent strains","volume":"54","author":"Zhang","year":"2010","journal-title":"Antimicrob. Agents. Chemother."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/j.micinf.2009.08.005","article-title":"Use of non-invasive bioluminescent imaging to assess mycobacterial dissemination in mice, treatment with bactericidal drugs and protective immunity","volume":"11","author":"Heuts","year":"2009","journal-title":"Microbes Infect."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ymeth.2017.03.022","article-title":"A high content microscopy assay to determine drug activity against intracellular Mycobacterium tuberculosis","volume":"127","author":"Manning","year":"2017","journal-title":"Methods"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/mmi.13626","article-title":"A high susceptibility to redox imbalance of the transmissible stages of Plasmodium falciparum revealed with a luciferase-based mature gametocyte assay","volume":"104","author":"Siciliano","year":"2017","journal-title":"Mol. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.ijmm.2007.09.004","article-title":"Lyme borreliosis spirochete Erp proteins, their known host ligands, and potential roles in mammalian infection","volume":"298","author":"Brissette","year":"2008","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1002\/bio.985","article-title":"Bioluminescence characteristics of a tropical terrestrial fungus (Basidiomycetes)","volume":"22","author":"Deheyn","year":"2007","journal-title":"Luminescence"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Chan, K., Alter, L., Barthold, S.W., and Parveen, N. (2015). Disruption of bbe02 by insertion of a luciferase gene increases transformation efficiency of Borrelia burgdorferi and allows live imaging in Lyme disease susceptible C3H mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129532"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chan, K., Awan, M., Barthold, S.W., and Parveen, N. (2012). Comparative molecular analyses of Borrelia burgdorferi sensu stricto strains B31 and N40D10\/E9 and determination of their pathogenicity. BMC Microbiol., 12.","DOI":"10.1186\/1471-2180-12-157"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1128\/IAI.06326-11","article-title":"Detection of established virulence genes and plasmids to differentiate Borrelia burgdorferi strains","volume":"80","author":"Chan","year":"2012","journal-title":"Infect. immun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11647","DOI":"10.1021\/bi050863a","article-title":"Transition state structure of 5\u2019-methylthioadenosine\/S-adenosylhomocysteine nucleosidase from Escherichia coli and its similarity to transition state analogues","volume":"44","author":"Singh","year":"2005","journal-title":"Biochemistry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4069","DOI":"10.1073\/pnas.1719504115","article-title":"Robust, linear correlations between growth rates and beta-lactam-mediated lysis rates","volume":"115","author":"Lee","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/S0969-2126(01)00656-6","article-title":"Structure of E. coli 5\u2019-methylthioadenosine\/S-adenosylhomocysteine nucleosidase reveals similarity to the purine nucleoside phosphorylases","volume":"9","author":"Lee","year":"2001","journal-title":"Structure"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1107\/S0907444900014669","article-title":"Expression, purification, crystallization and preliminary X-ray analysis of Escherichia coli 5\u2019-methylthioadenosine\/S-adenosylhomocysteine nucleosidase","volume":"57","author":"Lee","year":"2001","journal-title":"Acta. Crystallogr. D. Biol. Crystallogr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5159","DOI":"10.1021\/bi035492h","article-title":"Structural comparison of MTA phosphorylase and MTA\/AdoHcy nucleosidase explains substrate preferences and identifies regions exploitable for inhibitor design","volume":"43","author":"Lee","year":"2004","journal-title":"Biochemistry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1111\/j.1742-4658.2007.05784.x","article-title":"Biochemical and structural characterization of mammalian-like purine nucleoside phosphorylase from the Archaeon Pyrococcus furiosus","volume":"274","author":"Cacciapuoti","year":"2007","journal-title":"FEBS J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1006\/prep.1999.1076","article-title":"Heterologous expression of 5\u2019-methylthioadenosine phosphorylase from the archaeon Sulfolobus solfataricus: Characterization of the recombinant protein and involvement of disulfide bonds in thermophilicity and thermostability","volume":"16","author":"Cacciapuoti","year":"1999","journal-title":"Protein Expr. Purif."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s00792-002-0307-2","article-title":"Purification and characterization of 5\u2019-methylthioadenosine phosphorylase from the hyperthermophilic archaeon Pyrococcus furiosus: Substrate specificity and primary structure analysis","volume":"7","author":"Cacciapuoti","year":"2003","journal-title":"Extremophiles"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.1128\/IAI.74.5.3016-3020.2006","article-title":"Bgp, a secreted GAG-binding protein of B. burgdorferi strain N40, displays nucleosidase activity and is not essential for infection of immunodeficient mice","volume":"74","author":"Parveen","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1016\/j.cell.2019.04.016","article-title":"A White-Box Machine Learning Approach for Revealing Antibiotic Mechanisms of Action","volume":"177","author":"Yang","year":"2019","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1021\/bi301098g","article-title":"Affinity labeling of hepatitis C virus replicase with a nucleotide analogue: Identification of binding site","volume":"52","author":"Manvar","year":"2013","journal-title":"Biochemistry"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/0006-2952(85)90044-9","article-title":"5\u2019-Deoxy-5\u2019-methylthioadenosine phosphorylase--III. Role of the enzyme in the metabolism and action of 5\u2019-halogenated adenosine analogs","volume":"34","author":"Savarese","year":"1985","journal-title":"Biochem. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"8761","DOI":"10.1074\/jbc.M210836200","article-title":"Structure of Escherichia coli 5\u2019-methylthioadenosine\/ S-adenosylhomocysteine nucleosidase inhibitor complexes provide insight into the conformational changes required for substrate binding and catalysis","volume":"278","author":"Lee","year":"2003","journal-title":"J. Biol. Chem."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/9\/678\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:04:24Z","timestamp":1760177064000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/9\/678"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,20]]},"references-count":58,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["pathogens9090678"],"URL":"https:\/\/doi.org\/10.3390\/pathogens9090678","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,20]]}}}