Mechanism-based inhibition of HsaD: a C-C bond hydrolase essential for survival of Mycobacterium tuberculosis in macrophage

作者：Ryan Ali^*; Keany Sebastian; Eleftheriadou Olga; Ballet Romain; Cheng Hung Yuan; Sim Edith

来源：FEMS Microbiology Letters, 2014, 350(1): 42-47.

DOI：10.1111/1574-6968.12302

• HsaD
• Mycobacterium tuberculosis
• inhibitors
• mechanism
• MCP hydrolase
• cholesterol

Mycobacterium tuberculosis remains the leading cause of death by a bacterial pathogen worldwide. Increasing prevalence of multidrug-resistant organisms means prioritizing identification of targets for antituberculars. 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate hydrolase (HsaD), part of the cholesterol metabolism operon, is vital for survival within macrophage. The C-C bond hydrolase, HsaD, has a serine protease-like catalytic triad. We tested a range of serine protease and esterase inhibitors for their effects on HsaD activity. As well as providing a potential starting point for drug development, the data provides evidence for the mechanism of C-C bond hydrolysis. This screen also provides a route to initiate development of fragment-based inhibitors.

• 出版日期2014-1