Kinetic and equilibrium mechanisms of substrate binding to Mycobacterium tuberculosis enoyl reductase: implications to function-based antitubercular agent design
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , |
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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Journal of the Brazilian Chemical Society (Online) |
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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 |
_version_ |
1750318171118632960 |