The Octahydroindene Carboxyl Substructure from Dihydrobetulinic Acid is Essential to Inhibit Topoisomerase IB from Leishmania donovani
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.5935/0103-5053.20150295 http://hdl.handle.net/11449/161337 |
Resumo: | The dihydrobetulinic acid is a known competitive inhibitor of topoisomerase IB from Leishmania donovani, a validated target for developing new antileishmanial drugs. However, its binding mode and interaction pocket have not been established yet. We combined docking and molecular dynamics simulations to identify the most probable binding pocket. Our best model strongly suggests a cavity involving the residues arginine 314 and arginine 410 from chain A, and the catalytic tyrosine 222 from chain B as the interaction site and a substructure of this terpene inhibitor as essential for the process of molecular recognition. Then, a new class of inhibitors with increased affinity could be designed by structure-based approaches. |
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Repositório Institucional da UNESP |
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2946 |
spelling |
The Octahydroindene Carboxyl Substructure from Dihydrobetulinic Acid is Essential to Inhibit Topoisomerase IB from Leishmania donovanileishmaniasistopoisomerase IBdihydrobetulinic aciddockingmolecular dynamicsThe dihydrobetulinic acid is a known competitive inhibitor of topoisomerase IB from Leishmania donovani, a validated target for developing new antileishmanial drugs. However, its binding mode and interaction pocket have not been established yet. We combined docking and molecular dynamics simulations to identify the most probable binding pocket. Our best model strongly suggests a cavity involving the residues arginine 314 and arginine 410 from chain A, and the catalytic tyrosine 222 from chain B as the interaction site and a substructure of this terpene inhibitor as essential for the process of molecular recognition. Then, a new class of inhibitors with increased affinity could be designed by structure-based approaches.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)PROPe-UNESP (Young Research)Univ Estadual Paulista, Inst Quim, Dept Bioquim & Tecnol Quim, CP 355, BR-14800060 Araraquara, SP, BrazilUniv Estadual Paulista, Inst Quim, Dept Bioquim & Tecnol Quim, CP 355, BR-14800060 Araraquara, SP, BrazilFAPESP: 2012/00360-4Soc Brasileira QuimicaUniversidade Estadual Paulista (Unesp)Rocha, Camila A. [UNESP]Sanches, Paulo R. S. [UNESP]Marchetto, Reinaldo [UNESP]Zottis, Aderson [UNESP]2018-11-26T16:28:06Z2018-11-26T16:28:06Z2016-03-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article591-598application/pdfhttp://dx.doi.org/10.5935/0103-5053.20150295Journal Of The Brazilian Chemical Society. Sao Paulo: Soc Brasileira Quimica, v. 27, n. 3, p. 591-598, 2016.0103-5053http://hdl.handle.net/11449/16133710.5935/0103-5053.20150295S0103-50532016000300591WOS:000372466500015S0103-50532016000300591.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal Of The Brazilian Chemical Society0,357info:eu-repo/semantics/openAccess2024-01-20T06:36:04Zoai:repositorio.unesp.br:11449/161337Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-01-20T06:36:04Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
The Octahydroindene Carboxyl Substructure from Dihydrobetulinic Acid is Essential to Inhibit Topoisomerase IB from Leishmania donovani |
title |
The Octahydroindene Carboxyl Substructure from Dihydrobetulinic Acid is Essential to Inhibit Topoisomerase IB from Leishmania donovani |
spellingShingle |
The Octahydroindene Carboxyl Substructure from Dihydrobetulinic Acid is Essential to Inhibit Topoisomerase IB from Leishmania donovani Rocha, Camila A. [UNESP] leishmaniasis topoisomerase IB dihydrobetulinic acid docking molecular dynamics |
title_short |
The Octahydroindene Carboxyl Substructure from Dihydrobetulinic Acid is Essential to Inhibit Topoisomerase IB from Leishmania donovani |
title_full |
The Octahydroindene Carboxyl Substructure from Dihydrobetulinic Acid is Essential to Inhibit Topoisomerase IB from Leishmania donovani |
title_fullStr |
The Octahydroindene Carboxyl Substructure from Dihydrobetulinic Acid is Essential to Inhibit Topoisomerase IB from Leishmania donovani |
title_full_unstemmed |
The Octahydroindene Carboxyl Substructure from Dihydrobetulinic Acid is Essential to Inhibit Topoisomerase IB from Leishmania donovani |
title_sort |
The Octahydroindene Carboxyl Substructure from Dihydrobetulinic Acid is Essential to Inhibit Topoisomerase IB from Leishmania donovani |
author |
Rocha, Camila A. [UNESP] |
author_facet |
Rocha, Camila A. [UNESP] Sanches, Paulo R. S. [UNESP] Marchetto, Reinaldo [UNESP] Zottis, Aderson [UNESP] |
author_role |
author |
author2 |
Sanches, Paulo R. S. [UNESP] Marchetto, Reinaldo [UNESP] Zottis, Aderson [UNESP] |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Rocha, Camila A. [UNESP] Sanches, Paulo R. S. [UNESP] Marchetto, Reinaldo [UNESP] Zottis, Aderson [UNESP] |
dc.subject.por.fl_str_mv |
leishmaniasis topoisomerase IB dihydrobetulinic acid docking molecular dynamics |
topic |
leishmaniasis topoisomerase IB dihydrobetulinic acid docking molecular dynamics |
description |
The dihydrobetulinic acid is a known competitive inhibitor of topoisomerase IB from Leishmania donovani, a validated target for developing new antileishmanial drugs. However, its binding mode and interaction pocket have not been established yet. We combined docking and molecular dynamics simulations to identify the most probable binding pocket. Our best model strongly suggests a cavity involving the residues arginine 314 and arginine 410 from chain A, and the catalytic tyrosine 222 from chain B as the interaction site and a substructure of this terpene inhibitor as essential for the process of molecular recognition. Then, a new class of inhibitors with increased affinity could be designed by structure-based approaches. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-03-01 2018-11-26T16:28:06Z 2018-11-26T16:28:06Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.5935/0103-5053.20150295 Journal Of The Brazilian Chemical Society. Sao Paulo: Soc Brasileira Quimica, v. 27, n. 3, p. 591-598, 2016. 0103-5053 http://hdl.handle.net/11449/161337 10.5935/0103-5053.20150295 S0103-50532016000300591 WOS:000372466500015 S0103-50532016000300591.pdf |
url |
http://dx.doi.org/10.5935/0103-5053.20150295 http://hdl.handle.net/11449/161337 |
identifier_str_mv |
Journal Of The Brazilian Chemical Society. Sao Paulo: Soc Brasileira Quimica, v. 27, n. 3, p. 591-598, 2016. 0103-5053 10.5935/0103-5053.20150295 S0103-50532016000300591 WOS:000372466500015 S0103-50532016000300591.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal Of The Brazilian Chemical Society 0,357 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
591-598 application/pdf |
dc.publisher.none.fl_str_mv |
Soc Brasileira Quimica |
publisher.none.fl_str_mv |
Soc Brasileira Quimica |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1797790351037038592 |