Mechanism and Catalytic Site Atlas

Protein-glutamate methyl-esterase, also known as chemotaxis-specific methylesterase, is involved in regulating the signalling activity of bacterial chemotaxis transmembrane receptors through chemical modification of specific glutamate residues. The protein consists of two main domains, an N-terminal regulatory domain and a C-terminal effector domain. Phosphorylation of the N-terminal domain influences the reactivity of the catalytic C-terminus, although the truncated, C-terminus only protein retains full catalytic activity and substrate specificity [PMID:7608974].

The bacterial chemotaxis receptors are dimeric transmembrane proteins with periplasmic ligand-binding domains that detect specific chemoeffector molecules, and cytoplasmic domains that control the activities of intracellular signalling proteins. Like many of the response regulator proteins, it is a multi-domain protein consisting of an N-terminal regulatory domain and a C-terminal effector domain. Regulation of CheB involves both inter- and intramolecular interactions. The bacterial chemotaxis receptors control the activity of the first cytoplasmic component of the signal transduction pathway, the histidine protein kinase, CheA. The autophosphorylation activity of the CheA kinase is influenced by both the ligand occupancy of the receptors and the level of receptor methylation. Bacterial chemotaxis serves as a useful tool/model for the study of molecular strategies of signal transduction.

Methylester hydrolysis depends both on the conformation of the receptor and on phosphorylation of the Protein-glutamate methylesterase regulatory domain. Phosphorylation of the regulatory domain activates the effector function. The methylesterase active site is identified as a cleft at the C-terminal edge of the beta-sheet containing residues SER 164, HIS 190 and ASP 286. The three-dimensional fold, and the arrangement of residues within the catalytic triad distinguishes the CheB methyltransferase from any previously described serine protease or serine hydrolase. The three-dimensional arrangement of the catalytic triad in the CheB methyl transferase is different from that of previously characterised serine hydrolases and serine proteases due to the opposite orientation of the histidine residue - similar orientations are observed in thiol proteases papain and actinidin.