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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1ctt

E.C. namecytidine deaminase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 3.5.4.5
CSA Homologues of 1cttThere are 20 Homologs
CSA Entries With UniProtID P0ABF6
CSA Entries With EC Number 3.5.4.5
PDBe Entry 1ctt
PDBSum Entry 1ctt
MACiE Entry M0097

Literature Report

IntroductionCytidine deaminase catalyses the hydrolytic deamination of cytidine to uridine.
MechansimThe catalytic Zn ion is bound to histidine 102, cysteine 129, cysteine 132, and a catalytic water. The positive charge of the metal ion polarises the O-H bond in water, increasing its acidity towards the close proximity Glu104. Proton abstraction by the glutamate forms a hydroxide which acts as a nucleophile at the C2 of the substrate resulting in an anionic tetrahedral intermediate, which abstracts the proton from the glu104 in a concerted manner. Glutamate 104 then abstracts the hydroxide proton and the intermediate collapses leaving the amino group as free ammonia and uridine as the product.
Reaction

Catalytic Sites for 1ctt

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
CysA132132macie:sideChain The Zn-Cys132 bond has a unique capacity to buffer changes in net negative charge across the zince coordination sphere. This compensates for the developing negative charge on the substrate's 4-OH group as the reaction proceeds through the alkoxide character transition state. This valence-buffering may also be crucial in lowering the activation barrier associated with proton transfer steps in the hydration of the 3-4 N,C double bond.
GluA104104macie:sideChainThe residue acts as a general base to the hydrolytic water molecule held in the Zn coordination sphere, which then attacks the substrate in an addition reaction with concurrent deprotonation of Glu104. The resulting carboxylate deprotonates the substrate hydroxyl, resulting in the loss of ammonia through a E1cb mechanism with abstraction of the Glu104 proton.

Literature References

Notes:
Xiang S
Cytidine deaminase complexed to 3-deazacytidine: a "valence buffer" in zinc enzyme catalysis.
Biochemistry 1996 35 1335-1341
PubMed: 8634261
Xiang S
The structure of the cytidine deaminase-product complex provides evidence for efficient proton transfer and ground-state destabilization.
Biochemistry 1997 36 4768-4774
PubMed: 9125497
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