Crystal structure of the catalytic domain of the chemotaxis receptor methylesterase, CheB.

Signaling activity of bacterial chemotaxis transmembrane receptors is modulated by reversible covalent modification of specific receptor glutamate residues. The level of receptor methylation results from the activities of a specific S-adenosylmethionine-dependent methyltransferase, CheR, and the CheB methylesterase, which catalyzes hydrolysis of receptor glutamine or methylglutamate side-chains to glutamic acid. The CheB methylesterase belongs to a large family of response regulator proteins in which N-terminal regulatory domains control the activities of C-terminal effector domains. The crystal structure of the catalytic domain of the Salmonella typhimurium CheB methylesterase has been determined at 1.75 A resolution. The domain has a modified, doubly wound alpha/beta fold in which one of the helices is replaced by an anti-parallel beta-hairpin. Previous biochemical and mutagenesis data, suggest that the methylester hydrolysis catalyzed by CheB proceeds through a mechanism involving a serine nucleophile. The methylesterase active site is tentatively identified as a cleft at the C-terminal edge of the beta-sheet containing residues Ser164, His190 and Asp286. The three-dimensional fold, and the arrangement of residues within the catalytic triad distinguishes the CheB methylesterase from any previously described serine protease or serine hydrolase.