The Octahydroindene Carboxyl Substructure from Dihydrobetulinic Acid is Essential to Inhibit Topoisomerase IB from Leishmania donovani

Detalhes bibliográficos
Autor(a) principal: Rocha,Camila A.
Data de Publicação: 2016
Outros Autores: Sanches,Paulo R. S., Marchetto,Reinaldo, Zottis,Aderson
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Journal of the Brazilian Chemical Society (Online)
Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532016000300591
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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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.Sociedade Brasileira de Química2016-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532016000300591Journal of the Brazilian Chemical Society v.27 n.3 2016reponame:Journal of the Brazilian Chemical Society (Online)instname:Sociedade Brasileira de Química (SBQ)instacron:SBQ10.5935/0103-5053.20150295info:eu-repo/semantics/openAccessRocha,Camila A.Sanches,Paulo R. S.Marchetto,ReinaldoZottis,Adersoneng2016-03-10T00:00:00Zoai:scielo:S0103-50532016000300591Revistahttp://jbcs.sbq.org.brONGhttps://old.scielo.br/oai/scielo-oai.php||office@jbcs.sbq.org.br1678-47900103-5053opendoar:2016-03-10T00:00Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ)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.
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.
author_facet Rocha,Camila A.
Sanches,Paulo R. S.
Marchetto,Reinaldo
Zottis,Aderson
author_role author
author2 Sanches,Paulo R. S.
Marchetto,Reinaldo
Zottis,Aderson
author2_role author
author
author
dc.contributor.author.fl_str_mv Rocha,Camila A.
Sanches,Paulo R. S.
Marchetto,Reinaldo
Zottis,Aderson
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
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532016000300591
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532016000300591
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.5935/0103-5053.20150295
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Sociedade Brasileira de Química
publisher.none.fl_str_mv Sociedade Brasileira de Química
dc.source.none.fl_str_mv Journal of the Brazilian Chemical Society v.27 n.3 2016
reponame:Journal of the Brazilian Chemical Society (Online)
instname:Sociedade Brasileira de Química (SBQ)
instacron:SBQ
instname_str Sociedade Brasileira de Química (SBQ)
instacron_str SBQ
institution SBQ
reponame_str Journal of the Brazilian Chemical Society (Online)
collection Journal of the Brazilian Chemical Society (Online)
repository.name.fl_str_mv Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ)
repository.mail.fl_str_mv ||office@jbcs.sbq.org.br
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