Interaction of Mycobacterium tuberculosis CYP130 with heterocyclic arylamines.

ABSTRACT: The Mycobacterium tuberculosis P450 enzymes are of interest for their pharmacological development potential, as evidenced by their susceptibility to inhibition by antifungal azole drugs that normally target sterol 14alpha-demethylase (CYP51). Although antifungal azoles show promise, direct screening of compounds against M. tuberculosis P450 enzymes may identify novel, more potent, and selective inhibitory scaffolds. Here we report that CYP130 from M. tuberculosis has a natural propensity to bind primary arylamines with particular chemical architectures. These compounds were identified via a high throughput screen of CYP130 with a library of synthetic organic molecules. As revealed by subsequent x-ray structure analysis, selected compounds bind in the active site by Fe-coordination and hydr

SUBMITTER: Podust LM 

PROVIDER: S-EPMC2757224 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature