Kinetic evidence for interdomain communication in the allosteric regulation of alpha-isopropylmalate synthase from Mycobacterium tuberculosis.

ABSTRACT: The enzyme alpha-isopropylmalate synthase from Mycobacterium tuberculosis (MtIPMS) has been identified as a possible target for the design of new antitubercular therapeutics. Recently, it was shown that MtIPMS is subject to slow-onset, feedback inhibition by l-leucine, the first instance of an allosteric regulator utilizing this mechanism. Structural studies are inconsistent with canonical allosteric mechanisms, including changes to the quaternary structure or large, rigid-body conformational changes to the enzyme upon l-leucine binding. Thus, the allosteric regulation may result from a discrete inhibitory signal transmitted to the active site upon l-leucine binding in the regulatory domain, a distance of more than 50 A. To test this mechanism, site-directed mutagenesis was employed to con

SUBMITTER: de Carvalho LP 

PROVIDER: S-EPMC2724842 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature