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Catalytic Site Atlas

CSA LITERATURE entry for 1wd8

E.C. nameprotein-arginine deiminase
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz)
CSA Homologues of 1wd81wd9,1wda,2dew,2dex,2dey,2dw5,
CSA Entries With UniProtID Q9UM07
CSA Entries With EC Number
PDBe Entry 1wd8
PDBSum Entry 1wd8
MACiE Entry 1wd8

Literature Report

IntroductionProtein-arginine deiminase 4 catalyses the conversion of protein arginine residues to citrulline residues, and is calcium dependent.
The gene for this enzyme is a susceptibility locus for rheumatoid arthritis.
MechansimCalcium binding causes conformational changes that order the reaction centre. A nucleophilic attack is made by the thiol group of Cys 645 onto the zeta-carbon of peptidyl-L-arginine. The carboxyl groups of Asp 350 and Asp 473 activate the substrate by formation of hydrogen bonds and a salt bridge to increase the nucleophilicity of the zeta carbon. Cleavage of the bond between the zeta-carbon and the nu-nitrogen-2 to generate ammonia. The general base His 471 then activates water so that the water may undertake a nucleophilic attack. Hydrolysis of the tetrahedral adduct yields peptidyl-L-citrulline.

Catalytic Sites for 1wd8

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspA473473macie:sideChainActivates substrate by hydrogen bond and salt bridge formation.
AspA350350macie:sideChainThe carboxyl group activates the substrate by hydrogen bond and salt bridge formation.
CysA645645macie:sideChainThiol group attacks zeta-carbon of peptidyl-L-arginine as a nucleophile.
HisA471471macie:sideChainActs as a general base and activates water to allow water to attack as a nucleophile.

Literature References

Arita K
Structural basis for Ca(2+)-induced activation of human PAD4.
Nat Struct Mol Biol 2004 11 777-783
PubMed: 15247907
Kubota K
Determination of sites citrullinated by peptidylarginine deiminase using 18O stable isotope labeling and mass spectrometry.
Rapid Commun Mass Spectrom 2005 19 683-688
PubMed: 15700232