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

Journal of the Brazilian Chemical Society

Igor B. Vasconcelos¹  Luiz A. Basso¹  Diógenes S. Santos¹ 

[1] ,Pontifícia Universidade Católica do Rio Grande do Sul Instituto Nacional de Ciência e Tecnologia em Tuberculose Centro de Pesquisas em Biologia Molecular e FuncionalPorto Alegre RS ,Brazil

关键词: tuberculosis;    enoyl-ACP(CoA) reductase;    mycolic acid;    fluorescence titration;    pre-steady-state kinetics;   

DOI  :  10.1590/S0103-50532010000800014

来源: SciELO

【 摘 要 】

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.

【 授权许可】

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