Description

IPR000398 is a Thymidylate synthase.

<p>Thymidylate synthase ([ec:2.1.1.45]) [[cite:PUB00000031], [cite:PUB00000137]] catalyzes the reductive methylation of dUMP to dTMP with concomitant conversion of 5,10-methylenetetrahydrofolate to dihydrofolate: <reaction> 5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP </reaction> This provides the sole<i>de novo</i>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 [[cite:PUB00005100]]. 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 [[cite:PUB00002591]]. 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 [[cite:PUB00005100]]. A cysteine residue is involved in the catalytic mechanism (it covalently binds the 5,6-dihydro-dUMP intermediate) [[cite:PUB00036705], [cite:PUB00081481]]. The sequence around the active site of this enzyme is conserved from phages to vertebrates.</p> <p>Thymidylate synthase also acts as a regulator of its own expression by binding and inactivating its own RNA. Due to its key role in the de novo pathway for thymidylate synthesis and, hence, DNA synthesis, it is one of the most conserved enzymes across species and phyla [[cite:PUB00081476], [cite:PUB00037605]]. Thymidylate synthase is a well-recognized target for anticancer chemotherapy, as well as a valuable new target against infectious diseases [[cite:PUB00081477]]. Interestingly, in several protozoa, a single polypeptide chain codes for both dihydrofolate reductase (DHFR) and thymidylate synthase (TS), forming a bifunctional enzyme (DHFR-TS), possibly through gene fusion at a single evolutionary point. DHFR-TS is also active as a dimer [[cite:PUB00030463]].</p>

This description is obtained from EB-eye REST.

Associated GO terms

GO predictions are based solely on the InterPro-to-GO mappings published by EMBL-EBI, which are in turn based on the mapping of predicted domains to the InterPro dataset. The InterPro-to-GO mapping was last updated on April 27, 2020, while the GO metadata was last updated on April 27, 2020.

Associated Lotus transcripts 13

Co-occuring domains 1

A list of co-occurring predicted domains within the L. japonicus gene space: