Thymidylate synthase

Function

Catalyzes the reductive methylation of 2'-deoxyuridine-5'-monophosphate (dUMP) to 2'-deoxythymidine-5'-monophosphate (dTMP) while utilizing 5,10-methylenetetrahydrofolate (mTHF) as the methyl donor and reductant in the reaction, yielding dihydrofolate (DHF) as a by-product. This enzymatic reaction provides an intracellular de novo source of dTMP, an essential precursor for DNA biosynthesis. This protein also binds to its mRNA thus repressing its own translation.

Classification

Family (Pfam)

PF00303 Thymidylat_synt

InterPro

Thymidate_synth/dCMP_Mease, Thymidate_synth/dCMP_Mease_dom, Thymidate_synth/dCMP_Mease_sf, Thymidylate_synthase, Thymidylate_synthase_AS

Functional cluster

Central Metabolic Enzymes (KARI/Glycolysis)

Experimental structures · PDB · 67

• 1AIQ X-ray 2.20A
• 1AJM X-ray 2.40A
• 1AN5 X-ray 2.60A
• 1AOB X-ray 2.10A
• 1AXW X-ray 1.70A
• 1BDU X-ray 2.10A
• 1BID X-ray 2.20A
• 1BJG X-ray 2.30A
• 1BQ1 X-ray 2.50A
• 1BQ2 X-ray 2.20A
• 1DDU X-ray 2.10A
• 1DNA X-ray 2.20A
• … and 55 more

A predicted model is available from AlphaFold.

Gene Ontology · 10

• GO:0005829 cytosol
• GO:0000287 magnesium ion binding
• GO:0042803 protein homodimerization activity
• GO:0003723 RNA binding
• GO:0004799 thymidylate synthase activity
• GO:0006231 dTMP biosynthetic process
• GO:0006235 dTTP biosynthetic process
• GO:0032259 methylation
• GO:0006417 regulation of translation
• GO:0009314 response to radiation

Drugs targeting this protein · 2

• PEMETREXED TROMETHAMINE inhibitor
• PEMETREXED DIPOTASSIUM inhibitor

Related proteins · sequence + function similarity

• Thymidylate synthase 1.00
• Thymidylate synthase 1.00
• Thymidylate synthase 1.00
• Thymidylate synthase 1.00
• Thymidylate synthase 1.00
• Thymidylate synthase 1.00
• Thymidylate synthase 1.00
• Thymidylate synthase 1.00
• Thymidylate synthase 1.00
• Thymidylate synthase 1.00
• Thymidylate synthase 1.00
• Thymidylate synthase 1.00

Co-cited proteins · studied together in the literature

• Thymidylate synthase 1 shared papers
• Phosphatidylglycerol--prolipoprotein diacylglyceryl transferase 1 shared papers
• Uncharacterized protein YgdB 1 shared papers
• Prepilin peptidase-dependent protein A 1 shared papers
• Prepilin peptidase-dependent protein B 1 shared papers
• Prepilin peptidase-dependent protein C 1 shared papers
• RecBCD enzyme subunit RecC 1 shared papers

Literature · 15 cited papers

• Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol. Syst. Biol. · 2006
• Site-directed ligand discovery. Proc. Natl. Acad. Sci. U.S.A. · 2000
• Inactivity of N229A thymidylate synthase due to water-mediated effects: isolating a late stage in methyl transfer. J. Mol. Biol. · 1998
• Crystal structures of a marginally active thymidylate synthase mutant, Arg 126-->Glu. Protein Sci. · 1997
• Escherichia coli proteome analysis using the gene-protein database. Electrophoresis · 1997
• The complete genome sequence of Escherichia coli K-12. Science · 1997
• An essential role for water in an enzyme reaction mechanism: the crystal structure of the thymidylate synthase mutant E58Q. Biochemistry · 1996
• Water-mediated substrate/product discrimination: the product complex of thymidylate synthase at 1.83 A. Biochemistry · 1994
• Characterization of a specific interaction between Escherichia coli thymidylate synthase and Escherichia coli thymidylate synthase mRNA. Nucleic Acids Res. · 1995
• Primary structure of the Escherichia coli thyA gene and its thymidylate synthase product. Proc. Natl. Acad. Sci. U.S.A. · 1983
• Complete nucleotide sequence of the Escherichia coli recC gene and of the thyA-recC intergenic region. Nucleic Acids Res. · 1986
• Properties of a defined mutant of Escherichia coli thymidylate synthase. J. Biol. Chem. · 1988
• … and 3 more in the literature graph