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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1j79

E.C. namedihydroorotase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 3.5.2.3
CSA Homologues of 1j79There are 48 Homologs
CSA Entries With UniProtID P05020
CSA Entries With EC Number 3.5.2.3
PDBe Entry 1j79
PDBSum Entry 1j79
MACiE Entry 1j79

Literature Report

IntroductionDihyrdoorotase catalyses the reversible interconversion of carbamoyl aspartate and dihydroorotate. This reaction is an essential part of the pathway for the biosynthesis of pyrimidine nucleotides. Sequence comparisons show that there are two general classes of dihydroorotases. Class II enzymes are all monofunctional proteins from Gram-negative bacteria and yeast. Class I enzymes, found in higher organisms, are much larger and typically contain several enzyme activities as exemplified by CAD, a multifunctional enzyme found in mammals, insects and moulds. This protein combines the first three enzymes of the pyrimidine biosynthesis pathway: carbamoyl phosphate synthetase, aspartate carbamoylase, and dihydroorotase. Sequence homology within each class of enzymes is quite high (>40%) while that between the two classes is much lower. Both classes employ the same mechanism involving a binuclear zinc centre.
MechansimDihydroorotase uses a bi-nuclear zinc centre to catalyse the reversible formation and hydrolysis of dihydroorotate. In the hydrolysis reaction, the two zinc ions (alpha and beta) coordinate a bridging hydroxide ion that attacks the substrate carbonyl to form a tetrahedral intermediate. This process is facilitated by Asp 250 acting as a general base to deprotonate the attacking hydroxide, and by polarisation of the carbonyl group through coordination to the beta zinc ion. The tetrahedral intermediate and associated transition state is stabilised by coordination to both zinc ions. Collapse of this intermediate occurs with Asp 250 acting as a general acid to protate the departing amide nitrogen.
Reaction

Catalytic Sites for 1j79

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspA250251macie:sideChainActs as a general base to deprotonate the attacking bridging hydroxide. Later acts as a general acid to protonate the amide nitrogen leaving group.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspB250251macie:sideChainActs as a general base to deprotonate the attacking bridging hydroxide. Later acts as a general acid to protonate the amide nitrogen leaving group.

Literature References

Notes:
Porter TN
Mechanism of the dihydroorotase reaction.
Biochemistry 2004 43 16285-16292
PubMed: 15610022
Thoden JB
Molecular structure of dihydroorotase: a paradigm for catalysis through the use of a binuclear metal center.
Biochemistry 2001 40 6989-6997
PubMed: 11401542
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