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Ribbon Diagram Of Human Thymidylate Synthetase

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Thymidylate synthase
From Wikipedia, the free encyclopedia
Thymidylate synthetase
Thymidylate synthase 1HVY.png
Ribbon diagram of human thymidylate synthetase in complex with dUMP (orange) and raltitrexed (lime green). From PDB: 1HVY .
Available structures
PDB Ortholog search: PDBe, RCSB
[show]List of PDB id codes
Identifiers
Symbols TYMS ; HST422; TMS; TS
External IDs OMIM: 188350 MGI: 98878 HomoloGene: 834 ChEMBL: 1952 GeneCards: TYMS Gene
EC number 2.1.1.45
[show]Gene ontology
RNA expression pattern
PBB GE TYMS 202589 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 7298 22171
Ensembl ENSG00000176890 ENSMUSG00000025747
UniProt P04818 P07607
RefSeq (mRNA) NM_001071 NM_021288
RefSeq (protein) NP_001062
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Thymine is a nucleic acid in DNA. With inhibition of TS, an imbalance of deoxynucleotides and increased levels of dUTP arise. Both cause DNA damage.[2][3]

Contents [hide]
1 Function
2 Clinical significance
3 Using TS as a drug target
4 Interactive pathway map
5 Mechanism Description
6 See also
7 References
8 Further reading
9 External links
Function[edit]
The following reaction is catalyzed by thymidylate synthetase:

5,10-methylenetetrahydrofolate + dUMP ightleftharpoons dihydrofolate + dTMP
By means of reductive methylation, deoxyuridine monophosphate (dUMP) and N5,N10-methylene tetrahydrofolate are together used to form dTMP, yielding dihydrofolate as a secondary product.

This provides the sole de novo pathway for production of dTMP and is the only enzyme in folate metabolism in which the 5,10-methylenetetrahydrofolate is oxidised during one-carbon transfer.[4] The enzyme is essential for regulating the balanced supply of the 4 DNA precursors in normal DNA replication: defects in the enzyme activity affecting the regulation process cause various biological and genetic abnormalities, such as thymineless death.[5] The enzyme is an important target for certain chemotherapeutic drugs. Thymidylate synthase is an enzyme of about 30 to 35 Kd in most species except in protozoan and plants where it exists as a bifunctional enzyme that includes a dihydrofolate reductase domain.[4] A cysteine residue is involved in the catalytic mechanism (it
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