Kinetic and equilibrium mechanisms of substrate binding to Mycobacterium tuberculosis enoyl reductase: implications to function-based antitubercular agent design

Detalhes bibliográficos
Autor(a) principal: Vasconcelos,Igor B.
Data de Publicação: 2010
Outros Autores: Basso,Luiz A., Santos,Diógenes S.
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=S0103-50532010000800014
Resumo: Tuberculosis (TB) remains the leading cause of mortality due to a single bacterial pathogen, Mycobacterium tuberculosis. There is a need for the development of new antimycobacterial agents. M. tuberculosis 2-trans-enoyl-ACP(CoA) reductase (InhA) is the main target of isoniazid, the most prescribed anti-TB agent. Here we present pre-steady state kinetics and equilibrium data of 2-trans-dodecenoyl-CoA substrate binding to InhA. These results indicate both positive homotropic cooperativity upon substrate binding to InhA, and a bimolecular association process followed by a slow isomerization of the enzyme-substrate binary complex. The data here described should help the rational design of new agents against a validated and druggable protein target with potential anti-TB activity.
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spelling Kinetic and equilibrium mechanisms of substrate binding to Mycobacterium tuberculosis enoyl reductase: implications to function-based antitubercular agent designtuberculosisenoyl-ACP(CoA) reductasemycolic acidfluorescence titrationpre-steady-state kineticsTuberculosis (TB) remains the leading cause of mortality due to a single bacterial pathogen, Mycobacterium tuberculosis. There is a need for the development of new antimycobacterial agents. M. tuberculosis 2-trans-enoyl-ACP(CoA) reductase (InhA) is the main target of isoniazid, the most prescribed anti-TB agent. Here we present pre-steady state kinetics and equilibrium data of 2-trans-dodecenoyl-CoA substrate binding to InhA. These results indicate both positive homotropic cooperativity upon substrate binding to InhA, and a bimolecular association process followed by a slow isomerization of the enzyme-substrate binary complex. The data here described should help the rational design of new agents against a validated and druggable protein target with potential anti-TB activity.Sociedade Brasileira de Química2010-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532010000800014Journal of the Brazilian Chemical Society v.21 n.8 2010reponame:Journal of the Brazilian Chemical Society (Online)instname:Sociedade Brasileira de Química (SBQ)instacron:SBQ10.1590/S0103-50532010000800014info:eu-repo/semantics/openAccessVasconcelos,Igor B.Basso,Luiz A.Santos,Diógenes S.eng2011-10-14T00:00:00Zoai:scielo:S0103-50532010000800014Revistahttp://jbcs.sbq.org.brONGhttps://old.scielo.br/oai/scielo-oai.php||office@jbcs.sbq.org.br1678-47900103-5053opendoar:2011-10-14T00:00Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ)false
dc.title.none.fl_str_mv Kinetic and equilibrium mechanisms of substrate binding to Mycobacterium tuberculosis enoyl reductase: implications to function-based antitubercular agent design
title Kinetic and equilibrium mechanisms of substrate binding to Mycobacterium tuberculosis enoyl reductase: implications to function-based antitubercular agent design
spellingShingle Kinetic and equilibrium mechanisms of substrate binding to Mycobacterium tuberculosis enoyl reductase: implications to function-based antitubercular agent design
Vasconcelos,Igor B.
tuberculosis
enoyl-ACP(CoA) reductase
mycolic acid
fluorescence titration
pre-steady-state kinetics
title_short Kinetic and equilibrium mechanisms of substrate binding to Mycobacterium tuberculosis enoyl reductase: implications to function-based antitubercular agent design
title_full Kinetic and equilibrium mechanisms of substrate binding to Mycobacterium tuberculosis enoyl reductase: implications to function-based antitubercular agent design
title_fullStr Kinetic and equilibrium mechanisms of substrate binding to Mycobacterium tuberculosis enoyl reductase: implications to function-based antitubercular agent design
title_full_unstemmed Kinetic and equilibrium mechanisms of substrate binding to Mycobacterium tuberculosis enoyl reductase: implications to function-based antitubercular agent design
title_sort Kinetic and equilibrium mechanisms of substrate binding to Mycobacterium tuberculosis enoyl reductase: implications to function-based antitubercular agent design
author Vasconcelos,Igor B.
author_facet Vasconcelos,Igor B.
Basso,Luiz A.
Santos,Diógenes S.
author_role author
author2 Basso,Luiz A.
Santos,Diógenes S.
author2_role author
author
dc.contributor.author.fl_str_mv Vasconcelos,Igor B.
Basso,Luiz A.
Santos,Diógenes S.
dc.subject.por.fl_str_mv tuberculosis
enoyl-ACP(CoA) reductase
mycolic acid
fluorescence titration
pre-steady-state kinetics
topic tuberculosis
enoyl-ACP(CoA) reductase
mycolic acid
fluorescence titration
pre-steady-state kinetics
description Tuberculosis (TB) remains the leading cause of mortality due to a single bacterial pathogen, Mycobacterium tuberculosis. There is a need for the development of new antimycobacterial agents. M. tuberculosis 2-trans-enoyl-ACP(CoA) reductase (InhA) is the main target of isoniazid, the most prescribed anti-TB agent. Here we present pre-steady state kinetics and equilibrium data of 2-trans-dodecenoyl-CoA substrate binding to InhA. These results indicate both positive homotropic cooperativity upon substrate binding to InhA, and a bimolecular association process followed by a slow isomerization of the enzyme-substrate binary complex. The data here described should help the rational design of new agents against a validated and druggable protein target with potential anti-TB activity.
publishDate 2010
dc.date.none.fl_str_mv 2010-01-01
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=S0103-50532010000800014
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532010000800014
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.1590/S0103-50532010000800014
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.21 n.8 2010
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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