{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:30:26Z","timestamp":1762507826984,"version":"3.37.3"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T00:00:00Z","timestamp":1572480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100013778","name":"AJA University of Medical Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100013778","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Leishmania donovani, a parasitic protozoan causing visceral leishmaniasis, can lead to a dangerous and often fatal disease in humans. Current treatment for leishmaniasis may have severe side effects, low efficacy and high cost, hence an immediate need for new efficient drugs is essential. Arabinono-1, 4-lactone oxidase enzyme from Leishmania donovani (LdALO), which catalyzes the last step of the ascorbate biosynthesis pathway, has been considered as a potential target for antileishmanial drugs design.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The current study was performed with an in silico approach to predict novel inhibitory molecules against the LdALO enzyme. Various modeling and refinement processes were employed to obtain a reliable 3D structure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The best LdALO model with the highest qualitative model energy analysis score was predicted by the Robetta server and subsequently refined by 3D refine and ModLoop servers. The high quality of the final LdALO model was confirmed using model assessment software. Based on docking analysis results, we predicted 10 inhibitory molecules of a US Food and Drug Administration-approved library, with appropriate criteria regarding energy binding and interaction with the main functionally active sites of LdALO, indicating that they could be significant targets for further drug design investigations against L. donovani.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Suramin is used to treat the first stage of African sleeping sickness and its mechanism of action is unknown. Our results showed that suramin was the best-predicted inhibitor compound for LdALO enzyme activity.<\/jats:p><\/jats:sec>","DOI":"10.1093\/trstmh\/trz091","type":"journal-article","created":{"date-parts":[[2019,8,3]],"date-time":"2019-08-03T11:12:51Z","timestamp":1564830771000},"page":"162-172","source":"Crossref","is-referenced-by-count":4,"title":["Suramin could block the activity of Arabinono-1, 4-lactone oxidase enzyme from Leishmania donovani: structure-based screening and molecular dynamics analyses"],"prefix":"10.1093","volume":"114","author":[{"given":"Keivan","family":"Adinehbeigi","sequence":"first","affiliation":[{"name":"Department of Parasitology and Mycology, Faculty of Medicine, AJA University of Medical Sciences, Etemad Zadeh Street, Fatemi Street, Tehran, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minoo","family":"Shaddel","sequence":"first","affiliation":[{"name":"Department of Parasitology and Mycology, Faculty of Medicine, AJA University of Medical Sciences, Etemad Zadeh Street, Fatemi Street, Tehran, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saeed","family":"Khalili","sequence":"first","affiliation":[{"name":"Department of Biology Science, Shahid Rajaee University, Tehran, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alireza","family":"Zakeri","sequence":"first","affiliation":[{"name":"Department of Biology Science, Shahid Rajaee University, Tehran, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,10,31]]},"reference":[{"issue":"2","key":"2020031012572187500_ref1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.idc.2012.03.005","article-title":"Visceral leishmaniasis","volume":"26","author":"Griensven","year":"2012","journal-title":"Infect Dis Clin."},{"issue":"4","key":"2020031012572187500_ref2","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1080\/20477724.2017.1312777","article-title":"In vitro antileishmanial activity of fisetin flavonoid via inhibition of glutathione biosynthesis and arginase activity in Leishmania infantum","volume":"111","author":"Adinehbeigi","year":"2017","journal-title":"Pathog Glob Health."},{"issue":"4","key":"2020031012572187500_ref3","doi-asserted-by":"crossref","first-page":"778","DOI":"10.4269\/ajtmh.12-0442","article-title":"Visceral leishmaniasis prevalence and associated risk factors in the saran district of Bihar, India, from 2009 to July of 2011","volume":"88","author":"Perry","year":"2013","journal-title":"Am J Trop Med Hyg."},{"issue":"949","key":"2020031012572187500_ref4","first-page":"1","article-title":"World Health Organization. Report of a meeting of the WHO expert committee on the control of Leishmaniases, Geneva, Switzerland, 22-26 March 2010","volume":"2010","year":"2010","journal-title":"WHO Tech Rep Ser."},{"issue":"8","key":"2020031012572187500_ref5","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1007\/s12010-009-8764-z","article-title":"Rational approaches for drug designing against leishmaniasis","volume":"160","author":"Shukla","year":"2010","journal-title":"Appl Biochem Biotechnol."},{"issue":"1","key":"2020031012572187500_ref6","doi-asserted-by":"crossref","first-page":"42","DOI":"10.4103\/0972-9062.234625","article-title":"Cryotherapy of cutaneous leishmaniasis caused by Leishmania major in BALB\/c mice: a comparative experimental study","volume":"55","author":"Shaddel","year":"2018","journal-title":"J Vector Borne Dis."},{"issue":"15","key":"2020031012572187500_ref7","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1001\/jama.281.15.1415","article-title":"Criteria and recommendations for vitamin C intake","volume":"281","author":"Levine","year":"1999","journal-title":"JAMA."},{"issue":"4","key":"2020031012572187500_ref8","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1080\/07352680091139231","article-title":"Ascorbic acid in plants: biosynthesis and function","volume":"19","author":"Smirnoff","year":"2000","journal-title":"Crit Rev Plant Sci."},{"issue":"33","key":"2020031012572187500_ref9","doi-asserted-by":"crossref","first-page":"11645","DOI":"10.1073\/pnas.0504251102","article-title":"Vitamin C biosynthesis in trypanosomes: a role for the glycosome","volume":"102","author":"Wilkinson","year":"2005","journal-title":"Proc Natl Acad Sci."},{"issue":"4","key":"2020031012572187500_ref10","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1046\/j.1365-2958.1998.01133.x","article-title":"D-Erythroascorbic acid is an important antioxidant molecule in Saccharomyces cerevisiae","volume":"30","author":"Huh","year":"1998","journal-title":"Mol Microbiol."},{"issue":"3","key":"2020031012572187500_ref11","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1042\/BJ20070766","article-title":"The terminal step in vitamin C biosynthesis in Trypanosoma cruzi is mediated by a FMN-dependent galactonolactone oxidase","volume":"407","author":"Logan","year":"2007","journal-title":"Biochem J."},{"issue":"18","key":"2020031012572187500_ref12","doi-asserted-by":"crossref","first-page":"13685","DOI":"10.1016\/S0021-9258(17)36884-9","article-title":"Cloning and chromosomal mapping of the human nonfunctional gene for L-gulono-gamma-lactone oxidase, the enzyme for L-ascorbic acid biosynthesis missing in man","volume":"269","author":"Nishikimi","year":"1994","journal-title":"J Biol Chem."},{"issue":"2","key":"2020031012572187500_ref13","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.molbiopara.2011.08.005","article-title":"Leishmania donovani encodes a functional enzyme involved in vitamin C biosynthesis: Arabino-1, 4-lactone oxidase","volume":"180","author":"Biyani","year":"2011","journal-title":"Mol Biochem Parasitol."},{"issue":"suppl_2","key":"2020031012572187500_ref14","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1093\/nar\/gkh468","article-title":"Protein structure prediction and analysis using the Robetta server","volume":"32","author":"Kim","year":"2004","journal-title":"Nucleic Acids Res."},{"issue":"4","key":"2020031012572187500_ref15","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/nprot.2010.5","article-title":"I-TASSER: a unified platform for automated protein structure and function prediction","volume":"5","author":"Roy","year":"2010","journal-title":"Nat Protoc."},{"issue":"1","key":"2020031012572187500_ref16","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nmeth.3213","article-title":"The I-TASSER suite: Protein structure and function prediction","volume":"12","author":"Yang","year":"2015","journal-title":"Nat Methods."},{"issue":"2","key":"2020031012572187500_ref17","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1002\/prot.21945","article-title":"MUSTER: improving protein sequence profile-profile alignments by using multiple sources of structure information","volume":"72","author":"Wu","year":"2008","journal-title":"Proteins."},{"issue":"1","key":"2020031012572187500_ref18","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/prot.21715","article-title":"QMEAN: a comprehensive scoring function for model quality assessment","volume":"71","author":"Benkert","year":"2008","journal-title":"Proteins."},{"issue":"W1","key":"2020031012572187500_ref19","doi-asserted-by":"crossref","first-page":"W406","DOI":"10.1093\/nar\/gkw336","article-title":"3Drefine: an interactive web server for efficient protein structure refinement","volume":"44","author":"Bhattacharya","year":"2016","journal-title":"Nucleic Acids Res."},{"issue":"9","key":"2020031012572187500_ref20","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1110\/ps.9.9.1753","article-title":"Modeling of loops in protein structures","volume":"9","author":"Fiser","year":"2000","journal-title":"Protein Sci."},{"issue":"18","key":"2020031012572187500_ref21","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1093\/bioinformatics\/btg362","article-title":"ModLoop: automated modeling of loops in protein structures","volume":"19","author":"Fiser","year":"2003","journal-title":"Bioinformatics."},{"key":"2020031012572187500_ref22","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.toxicon.2017.01.010","article-title":"Structural pierce into molecular mechanism underlying Clostridium perfringens epsilon toxin function","volume":"127","author":"Khalili","year":"2017","journal-title":"Toxicon."},{"issue":"D1","key":"2020031012572187500_ref23","doi-asserted-by":"crossref","first-page":"D1074","DOI":"10.1093\/nar\/gkx1037","article-title":"DrugBank 5.0: a major update to the DrugBank database for 2018","volume":"46","author":"Wishart","year":"2017","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"2020031012572187500_ref24","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J Comput Chem."},{"issue":"11","key":"2020031012572187500_ref25","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1016\/j.freeradbiomed.2008.08.029","article-title":"Leishmania major ascorbate peroxidase overexpression protects cells against reactive oxygen species-mediated cardiolipin oxidation","volume":"45","author":"Dolai","year":"2008","journal-title":"Free Radic Biol Med."},{"issue":"1\u20132","key":"2020031012572187500_ref26","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0027-5107(01)00072-0","article-title":"Vitamin C and genomic stability","volume":"475","author":"Halliwell","year":"2001","journal-title":"Mutat Res-Fond Mol M."},{"issue":"10","key":"2020031012572187500_ref27","doi-asserted-by":"crossref","first-page":"6172","DOI":"10.1128\/AAC.02834-14","article-title":"Ascorbate peroxidase, a key molecule regulating amphotericin B resistance in clinical isolates of Leishmania donovani","volume":"58","author":"Kumar","year":"2014","journal-title":"Antimicrob Agents Chemother."},{"key":"2020031012572187500_ref28","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-7020-6285-8.00157-X","article-title":"Antiparasitic Agents","volume":"1345-72","author":"Kuhlmann","year":"2017","journal-title":"Infect Dis."},{"issue":"1","key":"2020031012572187500_ref29","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1186\/s13104-018-3446-y","article-title":"In vitro screening of known drugs identified by scaffold hopping techniques shows promising leishmanicidal activity for suramin and netilmicin","volume":"11","author":"Khanra","year":"2018","journal-title":"BMC Res Notes."},{"issue":"1","key":"2020031012572187500_ref30","doi-asserted-by":"crossref","first-page":"43","DOI":"10.4103\/0974-777X.93761","article-title":"Analyzing a potential drug target N-Myristoyltransferase of Plasmodium falciparum through in silico approaches","volume":"4","author":"Banerjee","year":"2012","journal-title":"J Glob Infect Dis."},{"key":"2020031012572187500_ref31","first-page":"18","article-title":"Immunoinformatics: Novel view in understanding of immune system function, databases and prediction of immunogenic epitopes","volume":"2015","author":"Ranjbar","journal-title":"Koomesh."},{"key":"2020031012572187500_ref32","first-page":"1","article-title":"Computational drug design and molecular dynamic studies-a review","volume":"5","author":"Maithri","year":"2016","journal-title":"Int J Biomed Data Min."},{"issue":"2","key":"2020031012572187500_ref33","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s12639-018-0996-9","article-title":"Bioinformatics analysis of single and multi-hybrid epitopes of GRA-1, GRA-4, GRA-6 and GRA-7 proteins to improve DNA vaccine design against Toxoplasma gondii","volume":"42","author":"Shaddel","year":"2018","journal-title":"J Parasit Dis."},{"issue":"6","key":"2020031012572187500_ref34","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/S1995-7645(12)60084-4","article-title":"Leishmaniasis: current status of available drugs and new potential drug targets","volume":"5","author":"Singh","year":"2012","journal-title":"Asian Pac J Trop Dis."},{"issue":"2","key":"2020031012572187500_ref35","doi-asserted-by":"crossref","first-page":"259","DOI":"10.4172\/pharmaceutical-sciences.1000111","article-title":"In silico analyses of Epicoccamides on selected Leishmania trypanothione reductase enzyme-based target","volume":"78","author":"Fatima","year":"2016","journal-title":"Indian J Pharm Sci."},{"issue":"1","key":"2020031012572187500_ref36","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/prot.24167","article-title":"3Drefine: consistent protein structure refinement by optimizing hydrogen bonding network and atomic-level energy minimization","volume":"81","author":"Bhattacharya","year":"2013","journal-title":"Proteins."},{"issue":"3","key":"2020031012572187500_ref37","doi-asserted-by":"crossref","DOI":"10.1002\/wcms.1307","article-title":"Computational protein structure refinement: almost there, yet still so far to go","volume":"7","author":"Feig","year":"2017","journal-title":"Wiley Interdiscip Rev Comput Mol Sci."},{"issue":"3","key":"2020031012572187500_ref38","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1093\/bioinformatics\/btq662","article-title":"Toward the estimation of the absolute quality of individual protein structure models","volume":"27","author":"Benkert","year":"2010","journal-title":"Bioinformatics."},{"issue":"11","key":"2020031012572187500_ref39","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1021\/jm051197e","article-title":"MolDock: a new technique for high-accuracy molecular docking","volume":"49","author":"Thomsen","year":"2006","journal-title":"J Med Chem."},{"issue":"7","key":"2020031012572187500_ref40","doi-asserted-by":"crossref","first-page":"13384","DOI":"10.3390\/molecules200713384","article-title":"Molecular docking and structure-based drug design strategies","volume":"20","author":"Ferreira","year":"2015","journal-title":"Molecules."},{"issue":"2","key":"2020031012572187500_ref41","doi-asserted-by":"publisher","DOI":"10.4172\/2329-9533.1000111","article-title":"Virtual screening and Pharmacophore analysis of potent antiviral inhibitors for viral proteins from Ebola virus","volume":"3","author":"Verma","year":"2014","journal-title":"J Appl Bioinform Comput Biol."},{"issue":"2","key":"2020031012572187500_ref42","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.sbi.2009.02.005","article-title":"Protein structure prediction: when is it useful?","volume":"19","author":"Zhang","year":"2009","journal-title":"Curr Opin Struct Biol."},{"issue":"1","key":"2020031012572187500_ref43","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/prot.21082","article-title":"Protein-ligand docking: current status and future challenges","volume":"65","author":"Sousa","year":"2006","journal-title":"Proteins."}],"container-title":["Transactions of The Royal Society of Tropical Medicine and Hygiene"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/trstmh\/article-pdf\/114\/3\/162\/32889275\/trz091.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/trstmh\/article-pdf\/114\/3\/162\/32889275\/trz091.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,21]],"date-time":"2024-07-21T17:29:19Z","timestamp":1721582959000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/trstmh\/article\/114\/3\/162\/5610283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,31]]},"references-count":43,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,10,31]]},"published-print":{"date-parts":[[2020,2,7]]}},"URL":"https:\/\/doi.org\/10.1093\/trstmh\/trz091","relation":{},"ISSN":["0035-9203","1878-3503"],"issn-type":[{"type":"print","value":"0035-9203"},{"type":"electronic","value":"1878-3503"}],"subject":[],"published-other":{"date-parts":[[2020,3]]},"published":{"date-parts":[[2019,10,31]]}}}