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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1xs1

E.C. namedCTP deaminase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 3.5.4.13
CSA Homologues of 1xs1
CSA Entries With UniProtID P28248
CSA Entries With EC Number 3.5.4.13
PDBe Entry 1xs1
PDBSum Entry 1xs1
MACiE Entry 1xs1

Literature Report

IntroductionDeoxycytidine triphosphate deaminase (dCTP deaminase) from E. coli catalyses the deamination of dCTP producing ammonia and dUTP. The dUTP can be hydrolysed by dUTPase producing dUMP which is a precursor of dTTP. dCTP deaminase is inhibited by dTTP and by inorganic phosphate. Deamination of dCTP by dCTP deaminase provides about 80% of the dUMP used for dTMP synthesis in E. coli.
The substrate of dCTP deaminase is the dCTP.Mg2+ complex but the magnesium does not have a catalytic role and no other metal ions are involved in catalysis. This pdb (1xs1) contains the structure of dCTP deaminase with the dUMP product bound to the active site.
MechansimGlu138 abstracts a proton from a water molecule (HOH5) creating a hydroxide ion which attacks C4 of the pyrimidine ring of dCTP forming a tetrahedral intermediate. The amine group on C4 is protonated by another water molecule (HOH251) and the tetrahedral intermediate breaks down releasing a molecule of ammonia. The hydroxide produced from HOH251 is then neutralised by a proton transferred from the intermediate via Glu138.
Reaction

Catalytic Sites for 1xs1

Annotated By Reference To The Literature - Site 7 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluA138138macie:sideChainGlu138 deprotonates water molecule HOH5 to create the hydroxide ion which acts as the nucleophile. It also protonates N3 on the substrate. Lastly it deprotonates the hydroxyl of the tetrahedral intermediate and transfers the proton to the hydroxide ion left behind by HOH251.
ArgA126126macie:sideChainPrevents the dCTP deaminase from also functioning as a dUTPase by taking up the space in which a nucleophilic water molecule could otherwise be located. This suggestion comes from a comparison of the E. coli dCTPdeaminase with the E. coli dUTPase. Arg126 also forms a salt bridge with Asp128.
AlaA124124macie:mainChainCarbonylHelps stabilise the hydroxide ion in the active site.
SerC111111macie:sideChainStabilises and positions the hydroxide ion in the active site.
ArgC115115macie:sideChainArg115 forms a hydrogen bond to Ser111 and prevents it's deprotonation by the hydroxide ion. The positive charge on Arg115 may also polarise the substrate for attack by the hydroxide ion.

Annotated By Reference To The Literature - Site 8 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluB138138macie:sideChainError
ArgB126126macie:sideChainError
AlaB124124macie:sideChainError

Annotated By Reference To The Literature - Site 9 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluC138138macie:sideChainError
ArgC126126macie:sideChainError
AlaC124124macie:sideChainError

Annotated By Reference To The Literature - Site 10 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluD138138macie:sideChainError
ArgD126126macie:sideChainError
AlaD124124macie:sideChainError

Annotated By Reference To The Literature - Site 11 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluE138138macie:sideChainError
ArgE126126macie:sideChainError
AlaE124124macie:sideChainError

Annotated By Reference To The Literature - Site 12 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluF138138macie:sideChainError
ArgF126126macie:sideChainError
AlaF124124macie:sideChainError

Annotated By Reference To The Literature - Site 13 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluA138138macie:sideChainGlu138 deprotonates water molecule HOH5 to create the hydroxide ion which acts as the nucleophile. It also protonates N3 on the substrate. Lastly it deprotonates the hydroxyl of the tetrahedral intermediate and transfers the proton to the hydroxide ion left behind by HOH251.
ArgA126126macie:sideChainPrevents the dCTP deaminase from also functioning as a dUTPase by taking up the space in which a nucleophilic water molecule could otherwise be located. This suggestion comes from a comparison of the E. coli dCTPdeaminase with the E. coli dUTPase. Arg126 also forms a salt bridge with Asp128.
AlaA124124macie:mainChainCarbonylHelps stabilise the hydroxide ion in the active site.
SerC111111macie:sideChainStabilises and positions the hydroxide ion in the active site.
ArgC115115macie:sideChainArg115 forms a hydrogen bond to Ser111 and prevents it's deprotonation by the hydroxide ion. The positive charge on Arg115 may also polarise the substrate for attack by the hydroxide ion.

Annotated By Reference To The Literature - Site 14 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerA111111macie:sideChainError
ArgA115115macie:sideChainError

Annotated By Reference To The Literature - Site 15 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerB111111macie:sideChainError
ArgB115115macie:sideChainError

Annotated By Reference To The Literature - Site 16 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerD111111macie:sideChainError
ArgD115115macie:sideChainError

Annotated By Reference To The Literature - Site 17 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerE111111macie:sideChainError
ArgE115115macie:sideChainError

Annotated By Reference To The Literature - Site 18 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerF111111macie:sideChainError
ArgF115115macie:sideChainError

Literature References

Notes:
Johansson E
Structures of dCTP deaminase from Escherichia coli with bound substrate and product: reaction mechanism and determinants of mono- and bifunctionality for a family of enzymes.
J Biol Chem 2005 280 3051-3059
PubMed: 15539408
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