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Catalytic Site Atlas

CSA LITERATURE entry for 1b5d

E.C. namedeoxycytidylate 5-hydroxymethyltransferase
SpeciesBacteriophage t4 (Virus)
E.C. Number (IntEnz) 2.1.2.8
CSA Homologues of 1b5d
CSA Entries With UniProtID P08773
CSA Entries With EC Number 2.1.2.8
PDBe Entry 1b5d
PDBSum Entry 1b5d
MACiE Entry 1b5d

Literature Report

IntroductionDeoxycytidylate (dCMP) 5-hydroxymethylase (CH) of bacteriophage T4 catalyses the addition of a protective hydroxymethyl group to cytosine monophosphate as a method of avoiding digestion by the host restriction systems. It requires the presence of methylenetetrahydrofolate (CH2THF)
MechansimGlu60 acts through a water molecule to donate a proton to N10 of CH2THF allowing the formation of an imminium ion at the N5 position. This later permits the donation of a methyl group to dCMP. The sulphur atom of Cys148 undergoes nucleophilic attack on the cytosine ring with the aid of Asp179 which donates a proton to the ring. Asp179 subsequently accepts the proton back, initiating attack on the carbon of the imminium ion by C5 of cytosine forming a bridging methyl group between the C5 of cytosine and N5 of THF. Cytosine loses a proton from the C5 position to reform the double bond and at the same time accepts a proton from Asp179. Loss of this proton to Asp179 causes a double bond to be formed at the new bridging methyl with concomitant lysis of the C-THF bond. The pi system is then attacked by water at the new carbon which causes the lysis of the bond to cystine. A loss of a proton from the water results in formation of the product .
Reaction

Catalytic Sites for 1b5d

Annotated By Reference To The Literature - Site 5 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspA179179macie:sideChainActs as a proton acceptor and donor to dCMP
GluA6060macie:sideChainPromotes the formation of the imminium ion form of C2THF through a water.
CysA148148macie:sideChainHolds dCMP in position during the reaction and activates the C5 position. Allows the final addition of water.

Annotated By Reference To The Literature - Site 6 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspB179179macie:sideChainActs as a proton acceptor and donor to dCMP
GluB6060macie:sideChainPromotes the formation of the imminium ion form of C2THF through a water.
CysB148148macie:sideChainHolds dCMP in position during the reaction and activates the C5 position. Allows the final addition of water.

Literature References

Notes:The cofactor C2THF was not crystalised with the enzyme.
Song HK
Crystal structure of deoxycytidylate hydroxymethylase from bacteriophage T4, a component of the deoxyribonucleoside triphosphate-synthesizing complex.
EMBO J 1999 18 1104-1113
PubMed: 10064578
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