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Thymidylate synthase

ID 2626
Name Thymidylate synthase
Synonyms
  • EC 2.1.1.45
  • TS
  • TSase
Gene Name thyA
Protein Sequence 
>Thymidylate synthase
MKQYLELMQKVLDEGTQKNDRTGTGTLSIFGHQMRFNLQDGFPLVTTKRCHLRSIIHELL
WFLQGDTNIAYLHENNVTIWDEWADENGDLGPVYGKQWRAWPTPDGRHIDQITTVLNQLK
NDPDSRRIIVSAWNVGELDKMALAPCHAFFQFYVADGKLSCQLYQRSCDVFLGLPFNIAS
YALLVHMMAQQCDLEVGDFVWTGGDTHLYSNHMDQTHLQLSREPRPLPKLIIKRKPESIF
DYRFEDFEIEGYDPHPGIKAPVAI
Number of Residues 264
Molecular Weight 30480
Theoretical pI 5.94
GO Classification
Function
methyltransferase activity
5,10-methylenetetrahydrofolate-dependent methyltransferase activity
thymidylate synthase activity
catalytic activity
transferase activity
transferase activity, transferring one-carbon groups
Process
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
nucleotide metabolism
pyrimidine nucleotide metabolism
pyrimidine nucleotide biosynthesis
physiological process
pyrimidine nucleoside monophosphate biosynthesis
pyrimidine deoxyribonucleoside monophosphate biosynthesis
metabolism
dTMP biosynthesis
cellular metabolism
General Function Nucleotide transport and metabolism
Specific Function Provides the sole de novo source of dTMP for DNA biosynthesis. This protein also binds to its mRNA thus repressing its own translation
Pathways Not Available
Reactions
  • 5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP
Pfam Domain Function
Signals None
Transmembrane Regions None
Essentiality Non-Essential
GenBank Protein ID 147987 Link_out
UniProtKB ID P0A884 Link_out
UniProtKB Entry Name TYSY_ECOLI Link_out
PDB ID 2KCE Link_out
PDB File show
3D Structure View 3D Structure
Cellular Location Cytoplasm
Gene Sequence 
>795 bp
ATGAAACAGTATTTAGAACTGATGCAAAAAGTGCTCGACGAAGGCACACAGAAAAACGAC
CGTACCGGAACCGGAACGCTTTCCATTTTTGGTCATCAGATGCGTTTTAACCTGCAAGAT
GGATTCCCGCTGGTGACAACTAAACGTTGCCACCTGCGTTCCATCATCCATGAACTGCTG
TGGTTTCTGCAGGGCGACACTAACATTGCTTATCTACACGAAAACAATGTCACCATCTGG
GACGAATGGGCCGATGAAAACGGCGACCTCGGGCCAGTGTATGGTAAACAGTGGCGCGCC
TGGCCAACGCCAGATGGTCGTCATATTGACCAGATCACTACGGTACTGAACCAGCTGAAA
AACGACCCGGATTCGCGCCGCATTATTGTTTCAGCGTGGAACGTAGGCGAACTGGATAAA
ATGGCGCTGGCACCGTGCCATGCATTCTTCCAGTTCTATGTGGCAGACGGCAAACTCTCT
TGCCAGCTTTATCAGCGCTCCTGTGACGTCTTCCTCGGCCTGCCGTTCAACATTGCCAGC
TACGCGTTATTGGTGCATATGATGGCGCAGCAGTGCGATCTGGAAGTGGGTGATTTTGTC
TGGACCGGTGGCGACACGCATCTGTACAGCAACCATATGGATCAAACTCATCTGCAATTA
AGCCGCGAACCGCGTCCGCTGCCGAAGTTGATTATCAAACGTAAACCCGAATCCATCTTC
GACTACCGTTTCGAAGACTTTGAGATTGAAGGCTACGATCCGCATCCGGGCATTAAAGCG
CCGGTGGCTATCTAA
GenBank Gene ID J01710 Link_out
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
HPRD ID Not Available
IUPHAR ID Not Available
Guide to Pharmacology ID Not Available
Chromosome Location Not Available
Locus Not Available
SNPs thyA Link_out
General References
  1. Belfort M, Maley G, Pedersen-Lane J, Maley F: Primary structure of the Escherichia coli thyA gene and its thymidylate synthase product. Proc Natl Acad Sci U S A. 1983 Aug;80(16):4914-8. Pubmed
  2. Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-74. Pubmed
  3. Finch PW, Wilson RE, Brown K, Hickson ID, Tomkinson AE, Emmerson PT: Complete nucleotide sequence of the Escherichia coli recC gene and of the thyA-recC intergenic region. Nucleic Acids Res. 1986 Jun 11;14(11):4437-51. Pubmed
  4. Montfort WR, Perry KM, Fauman EB, Finer-Moore JS, Maley GF, Hardy L, Maley F, Stroud RM: Structure, multiple site binding, and segmental accommodation in thymidylate synthase on binding dUMP and an anti-folate. Biochemistry. 1990 Jul 31;29(30):6964-77. Pubmed
  5. Voeller DM, Changchien LM, Maley GF, Maley F, Takechi T, Turner RE, Montfort WR, Allegra CJ, Chu E: Characterization of a specific interaction between Escherichia coli thymidylate synthase and Escherichia coli thymidylate synthase mRNA. Nucleic Acids Res. 1995 Mar 11;23(5):869-75. Pubmed
  6. Kim CW, Michaels ML, Miller JH: Amino acid substitution analysis of E. coli thymidylate synthase: the study of a highly conserved region at the N-terminus. Proteins. 1992 Aug;13(4):352-63. Pubmed
  7. Perry KM, Fauman EB, Finer-Moore JS, Montfort WR, Maley GF, Maley F, Stroud RM: Plastic adaptation toward mutations in proteins: structural comparison of thymidylate synthases. Proteins. 1990;8(4):315-33. Pubmed
  8. Fauman EB, Rutenber EE, Maley GF, Maley F, Stroud RM: Water-mediated substrate/product discrimination: the product complex of thymidylate synthase at 1.83 A. Biochemistry. 1994 Feb 15;33(6):1502-11. Pubmed
  9. Sage CR, Rutenber EE, Stout TJ, Stroud RM: An essential role for water in an enzyme reaction mechanism: the crystal structure of the thymidylate synthase mutant E58Q. Biochemistry. 1996 Dec 17;35(50):16270-81. Pubmed
  10. Strop P, Changchien L, Maley F, Montfort WR: Crystal structures of a marginally active thymidylate synthase mutant, Arg 126—>Glu. Protein Sci. 1997 Dec;6(12):2504-11. Pubmed
  11. Reyes CL, Sage CR, Rutenber EE, Nissen RM, Finer-Moore JS, Stroud RM: Inactivity of N229A thymidylate synthase due to water-mediated effects: isolating a late stage in methyl transfer. J Mol Biol. 1998 Dec 4;284(3):699-712. Pubmed
  12. Erlanson DA, Braisted AC, Raphael DR, Randal M, Stroud RM, Gordon EM, Wells JA: Site-directed ligand discovery. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9367-72. Pubmed
Drugs
# DrugBank ID Drug Name Drug Type Drug Groups
1 DB02031 (6s)-5,6,7,8-Tetrahydrofolate small molecule experimental
2 DB04447 1,4-Dithiothreitol small molecule experimental
3 DB03541 10-Propargyl-5,8-Dideazafolic Acid small molecule experimental
4 DB08131 2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-3-METHYL-BUTYRIC ACID small molecule experimental
5 DB04586 2-bromophenol small molecule experimental
6 DB03274 2'-5'dideoxyuridine small molecule experimental
7 DB04457 2'-Deoxyguanosine-5'-Monophosphate small molecule experimental
8 DB02256 2'-Deoxyuridine small molecule experimental
9 DB03800 2'-deoxyuridylic acid small molecule experimental
10 DB04696 4-CHLORO-3',3''-DIBROMOPHENOL-1,8-NAPHTHALEIN small molecule experimental
11 DB03761 5-Fluoro-2'-Deoxyuridine-5'-Monophosphate small molecule experimental
12 DB02301 5,10-Methylene-6-Hydrofolic Acid small molecule experimental
13 DB02223 Ly231514 Tetra Glu small molecule experimental
14 DB03038 LY341770 small molecule experimental
15 DB03818 N-[Tosyl-D-Prolinyl]Amino-Ethanethiol small molecule experimental
16 DB02899 N-Carboxymethionine small molecule experimental
17 DB03157 N,O-Didansyl-L-Tyrosine small molecule experimental
18 DB02467 S-Oxymethionine small molecule experimental
19 DB04530 S,S-(2-Hydroxyethyl)Thiocysteine small molecule experimental
20 DB04503 Sp-722 small molecule experimental
21 DB03558 Sp-876 small molecule experimental
22 DB02752 Tosyl-D-Proline small molecule experimental