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Catalytic Site Atlas

CSA LITERATURE entry for 1b02

E.C. namethymidylate synthase
SpeciesBacillus subtilis (Bacteria)
E.C. Number (IntEnz) 2.1.1.45
CSA Homologues of 1b02There are 125 Homologs
CSA Entries With UniProtID P0CI79
CSA Entries With EC Number 2.1.1.45
PDBe Entry 1b02
PDBSum Entry 1b02
MACiE Entry 1b02

Literature Report

IntroductionThymidylate synthase catalyses the reductive methylation of dUMP by CH2H4-folate to produce dTMP and H2-folate. It is unique among enzymes that use folate cofactors in that CH2H4-folate serves as both a one-carbon donor and reductant, and H2-folate is a product. dTMP is subsequently phosphorylated by another enzyme to thymidine triphosphate for use in DNA synthesis and repair.
MechansimThe mechanism has four steps: 1)Activation of C-5 of dUMP for substitution. 2)Activation of CH2H4-folate. 3)Transfer of methylene group from CH2H4-folate to dUMP. 4)Reduction of transferred methylene group.
Reaction

Catalytic Sites for 1b02

Literature References

Notes:
Carreras CW
The catalytic mechanism and structure of thymidylate synthase.
Annu Rev Biochem 1995 64 721-762
PubMed: 7574499
Finer-Moore JS
Lessons and conclusions from dissecting the mechanism of a bisubstrate enzyme: thymidylate synthase mutagenesis, function, and structure.
Biochemistry 2003 42 248-256
PubMed: 12525151
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