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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1pya

E.C. namehistidine decarboxylase
SpeciesLactobacillus sp. (strain 30a)
E.C. Number (IntEnz) 4.1.1.22
CSA Homologues of 1pya1hq6,1ibt,1ibu,1ibv,1ibw,
CSA Entries With UniProtID P00862
CSA Entries With EC Number 4.1.1.22
PDBe Entry 1pya
PDBSum Entry 1pya
MACiE Entry M0049

Literature Report

IntroductionHistidine decarboxylasses from Lactobacillus 30a is the best-studied of a class of enzyme which utilise the covalently bound cofactor, pyruvate. Models of the active site with and without the bound substrate analogue, histidine methyl ester (HisOMe), or the product, histamine, have been produced. Comparison of native and ligand-bound structures reveals no widespread differences in conformation but does reveal motion of a few key residues.
The native enzyme is an (alpha-beta)6 "hexamer". Two trimers bind bottom-to-bottom across a crystallographic dyad, forming a dumbell-shaped hexamer with cavities at either end.
Mechansim The binding site contains two pockets, one for the imidazole group, and another one for the carboxyl -COOMe group.
The mechanism of histidine decarboxylation can be divided into three parts i) forming the Schiff base ii) decarboxylation/reprotonation iii) breaking tMAP00340 Histidine metabolism Schiff base.
The substrate first condenses with the pyruvoyl residue Prv-82 to form a Schiff base in which the substrate amine nitrogen is bonded to the alpha-carbon of Prv. As the carboxyl group of the substrate is removed, its negative charge passes to the alpha-carbon of the substrate, creating a transient carbanion. The Schiff base acts as a bridge - permitting resonance stabilisation of this alpha-carbon bond by the cofactor (acts as an electron sink). After the release of carbon dioxide, the alpha-carbon captures a proton from a suitable donor and the product is now ready to be freed by hydrolysis of the Schiff base.
Reaction

Catalytic Sites for 1pya

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
TyrA6263macie:sideChain
PheF195196macie:mainChainAmide
GluF197198macie:sideChain
SerE8182macie:sideChain

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerA8182macie:sideChain
TyrC6263macie:sideChain
PheB195196macie:mainChainAmide
GluB197198macie:sideChain

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerC8182macie:sideChainError
PheD195196macie:sideChainError
GluD197198macie:sideChainError
TyrE6263macie:sideChainError

Literature References

Notes:
Gallagher T
Pyruvoyl-dependent histidine decarboxylase. Active site structure and mechanistic analysis.
J Biol Chem 1989 264 12737-12743
PubMed: 2745463
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