Inactivation of the Mycobacterium tuberculosis antigen 85 complex by covalent, allosteric inhibitors.

ABSTRACT: The rise of multidrug-resistant and totally drug-resistant tuberculosis and the association with an increasing number of HIV-positive patients developing tuberculosis emphasize the necessity to find new antitubercular targets and drugs. The antigen 85 (Ag85) complex from Mycobacterium tuberculosis plays important roles in the biosynthesis of major components of the mycobacterial cell envelope. For this reason, Ag85 has emerged as an attractive drug target. Recently, ebselen was identified as an effective inhibitor of the Ag85 complex through covalent modification of a cysteine residue proximal to the Ag85 active site and is therefore a covalent, allosteric inhibitor. To expand the understanding of this process, we have solved the x-ray crystal structures of Ag85C covalently modified with e

SUBMITTER: Favrot L 

PROVIDER: S-EPMC4155670 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature