Crystal structure of the chemotaxis receptor methyltransferase CheR suggests a conserved structural motif for binding S-adenosylmethionine

Abstract

The CheR structure shares some structural similarities with small molecule DNA and RNA methyltransferases, despite a lack of sequence similarity among them. In particular, there is significant structural preservation of the S-adenosylmethionine-binding clefts; the specific length and conformation of a loop in the alpha/beta domain seems to be required for S-adenosylmethionine binding within these enzymes. Unique structural features of CheR, such as the beta subdomain, are probably necessary for CheR's specific interaction with its substrates, the bacterial chemotaxis receptors.

Discrimination between Different Methylation States of Chemotaxis Receptor Tar by Receptor Methyltransferase CheR

“…CheR is composed of a small N-terminal domain and a larger C-terminal domain with a seven-stranded modified Rossmann nucleotide-binding fold characteristic of class I methyltransferases (18,19). A small β-subdomain is inserted into the C-terminal domain of CheR.…”

A Unique Mechanism for Methyl Ester Formation via an Amide Intermediate Found in Myxobacteria

“…We have addressed this show that the amide moiety of myxothiazol A is hydrolyzed by MelJ resulting in the formation of myxothiazol acid which is subsequently methylated by MelK to the methyl ester ( Figure 3, pathway B). Interestingly, a similar mechanism of methyl ester formation is described for bacterial chemotaxis transmembrane factors in Salmonella typhimurium [25,26]. Theoretically, free melithiazol acid might alternatively be released by the hydrolase from the ACP of MelF and thus MelG might not be required for melithiazol biosynthesis.…”

Mapping and Molecular Modeling ofS-Adenosyl-l-methionine Binding Sites inN-Methyltransferase Domains of the Multifunctional Polypeptide Cyclosporin Synthetase

“…Early studies on the photochemical cross-linking of purines have shown that substitution/addition reactions can occur either across the 1,6 double bond (64) The AdoMet binding domain of MTases exhibits a comparable three-dimensional folding (27)(28)(29). This structural similarity extends to the tertiary positions of the amino acid side chains interacting with the AdoMet molecule.…”

“…Despite the poor overall sequence identity across AdoMet-dependent MTases and varied substrate specificity, these enzymes display a structurally conserved cofactorbinding domain termed the "AdoMet-binding fold" (27)(28)(29). Moreover, a structural conservation of the mode of cofactor binding is observed across most structurally defined members of this superfamily; this has led to the delineation of a set of consensus AdoMet binding interactions (28).…”