Conformational changes upon ligand binding in the essential class II fumarase Rv1098c from Mycobacterium tuberculosis.

Lien vers Pubmed [PMID] – 22561013

Lien DOI – 10.1016/j.febslet.2012.04.034

FEBS Lett 2012 Jun; 586(11): 1606-11

rv1098c, an essential gene in Mycobacterium tuberculosis, codes for a class II fumarase. We describe here the crystal structure of Rv1098c in complex with l-malate, fumarate or the competitive inhibitor meso-tartrate. The models reveal that substrate binding promotes the closure of the active site through conformational changes involving the catalytic SS-loop and the C-terminal domain, which likely represents a general feature of this enzyme superfamily. Analysis of ligand-enzyme interactions as well as site-directed mutagenesis suggest Ser318 as one of the two acid-base catalysts.