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Catalytic Site Atlas

CSA LITERATURE entry for 1chd

E.C. nameprotein-glutamate methylesterase
SpeciesSalmonella typhimurium (Bacteria)
E.C. Number (IntEnz) 3.1.1.61
CSA Homologues of 1chd1a2o,
CSA Entries With UniProtID P04042
CSA Entries With EC Number 3.1.1.61
PDBe Entry 1chd
PDBSum Entry 1chd
MACiE Entry M0337

Literature Report

IntroductionProtein-glutamate methylesterase is also known as chemotaxis-specific methylesterase. Signalling activity of bacterial chemotaxis transmembrane receptors is modulated by reversible methylation of specific receptor glutamate residues.
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.
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 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.
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.
Bacterial chemotaxis serves as a useful tool/model for the study of molecular strategies of signal transduction.
MechansimThe hydrolysis of carboxyl methyl groups and amide groups catalysed by the CheB methylesterase is expected to involve a catalytic mechanism similar to that of the serine proteases and other hydrolases.
The active site proposed is consistent with a proton relay mechanism proposed for hydrolysis by a serine nucleophile within a catalytic triad. For the hydrolysis catalysed by CheB, the proposed reaction mechanism would involve the hydroxyl group of Ser 164 as the nucleophile and the imidazole ring of His 190 as the proton donor to the leaving group, methanol. A potential oxyanion hole for stabilisation of the tetrahedral intermediate would be provided by the backbone amide groups of Met 283 and Thr165.
Reaction

Catalytic Sites for 1chd

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerA164164macie:sideChainhe residue acts as a nucleophile towards the carbonyl functionality of the carboxyl-methylglutamate residues of the receptor substrate, resulting in an anionic tetrahedral intermediate. The hydroxyl proton of the residue is relayed to His 190, and then to the methanol leaving group.
HisA190190macie:sideChainThe residue acts as a proton acceptor from the nucleophilic Ser164 and as a proton donor to the departing methanol. Hydrogen bonding interactions with Asp 286 orientates the residue for interaction with Ser164, and also modifies the pKa of the general acid imidazole nitrogen towards proton donation.
AspA286286macie:sideChainThe residue hydrogen bonds to the (E)N of the His190 imidazole ring, directing and stabilising the catalytic general base within the active site.
ThrA165165macie:mainChainAmideThe residue's backbone forms an oxyanion hole which stabilises the anionic tetrahedral intermediate.
MetA283283macie:mainChainAmideThe residue's backbone forms an oxyanion hole which stabilises the anionic tetrahedral intermediate.

Literature References

Notes:
West AH
Crystal structure of the catalytic domain of the chemotaxis receptor methylesterase, CheB.
J Mol Biol 1995 250 276-290
PubMed: 7608974
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