Research Letter: Mechanism-based inhibition of HsaD: a C-C bond hydrolase essential for survival of M. tuberculosis in macrophage

M. tuberculosis remains the leading cause of death by a bacterial pathogen worldwide. Increasing prevalence of multidrug resistant organisms means prioritising identification of targets for anti-tuberculars. 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. This article is protected by copyright. All rights reserved.