Thymidylate synthase

Details

Name
Thymidylate synthase
Synonyms
  • 2.1.1.45
  • TS
Gene Name
thyA
Organism
Escherichia coli (strain K12)
Amino acid sequence
>lcl|BSEQ0011008|Thymidylate synthase
MKQYLELMQKVLDEGTQKNDRTGTGTLSIFGHQMRFNLQDGFPLVTTKRCHLRSIIHELL
WFLQGDTNIAYLHENNVTIWDEWADENGDLGPVYGKQWRAWPTPDGRHIDQITTVLNQLK
NDPDSRRIIVSAWNVGELDKMALAPCHAFFQFYVADGKLSCQLYQRSCDVFLGLPFNIAS
YALLVHMMAQQCDLEVGDFVWTGGDTHLYSNHMDQTHLQLSREPRPLPKLIIKRKPESIF
DYRFEDFEIEGYDPHPGIKAPVAI
Number of residues
264
Molecular Weight
30479.475
Theoretical pI
5.94
GO Classification
Functions
RNA binding / thymidylate synthase activity
Processes
dTMP biosynthetic process / dTTP biosynthetic process / regulation of translation
Components
cytosol
General Function
Thymidylate synthase activity
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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0011009|Thymidylate synthase (thyA)
ATGAAACAGTATTTAGAACTGATGCAAAAAGTGCTCGACGAAGGCACACAGAAAAACGAC
CGTACCGGAACCGGAACGCTTTCCATTTTTGGTCATCAGATGCGTTTTAACCTGCAAGAT
GGATTCCCGCTGGTGACAACTAAACGTTGCCACCTGCGTTCCATCATCCATGAACTGCTG
TGGTTTCTGCAGGGCGACACTAACATTGCTTATCTACACGAAAACAATGTCACCATCTGG
GACGAATGGGCCGATGAAAACGGCGACCTCGGGCCAGTGTATGGTAAACAGTGGCGCGCC
TGGCCAACGCCAGATGGTCGTCATATTGACCAGATCACTACGGTACTGAACCAGCTGAAA
AACGACCCGGATTCGCGCCGCATTATTGTTTCAGCGTGGAACGTAGGCGAACTGGATAAA
ATGGCGCTGGCACCGTGCCATGCATTCTTCCAGTTCTATGTGGCAGACGGCAAACTCTCT
TGCCAGCTTTATCAGCGCTCCTGTGACGTCTTCCTCGGCCTGCCGTTCAACATTGCCAGC
TACGCGTTATTGGTGCATATGATGGCGCAGCAGTGCGATCTGGAAGTGGGTGATTTTGTC
TGGACCGGTGGCGACACGCATCTGTACAGCAACCATATGGATCAAACTCATCTGCAATTA
AGCCGCGAACCGCGTCCGCTGCCGAAGTTGATTATCAAACGTAAACCCGAATCCATCTTC
GACTACCGTTTCGAAGACTTTGAGATTGAAGGCTACGATCCGCATCCGGGCATTAAAGCG
CCGGTGGCTATCTAA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP0A884
UniProtKB Entry NameTYSY_ECOLI
GenBank Protein ID147987
GenBank Gene IDJ01710
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:6308660]
  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):1453-62. [PubMed:9278503]
  3. Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K, Choi S, Ohtsubo E, Baba T, Wanner BL, Mori H, Horiuchi T: Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol. 2006;2:2006.0007. Epub 2006 Feb 21. [PubMed:16738553]
  4. 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:3520484]
  5. VanBogelen RA, Abshire KZ, Moldover B, Olson ER, Neidhardt FC: Escherichia coli proteome analysis using the gene-protein database. Electrophoresis. 1997 Aug;18(8):1243-51. [PubMed:9298644]
  6. 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:2223754]
  7. 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:7708505]
  8. 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:1518803]
  9. 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:2128651]
  10. 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:8312270]
  11. 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:8973201]
  12. 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:9416600]
  13. 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:9826509]
  14. 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:10944209]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02031(6S)-5,6,7,8-tetrahydrofolateexperimentalunknownDetails
DB02223LY231514 Tetra GluexperimentalunknownDetails
DB022562'-DeoxyuridineexperimentalunknownDetails
DB023015,10-Methylene-6-Hydrofolic AcidexperimentalunknownDetails
DB02467L-methionine (S)-S-oxideexperimentalunknownDetails
DB02752Tosyl-D-ProlineexperimentalunknownDetails
DB02899N-CarboxymethionineexperimentalunknownDetails
DB03038LY341770experimentalunknownDetails
DB03157N,O-Didansyl-L-TyrosineexperimentalunknownDetails
DB032742'-5'dideoxyuridineexperimentalunknownDetails
DB0354110-Propargyl-5,8-Dideazafolic AcidexperimentalunknownDetails
DB03558Sp-876experimentalunknownDetails
DB037615-Fluoro-2'-Deoxyuridine-5'-MonophosphateexperimentalunknownDetails
DB03800Deoxyuridine monophosphateexperimentalunknownDetails
DB03818N-[Tosyl-D-Prolinyl]Amino-EthanethiolexperimentalunknownDetails
DB044471,4-DithiothreitolexperimentalunknownDetails
DB044572'-Deoxyguanosine-5'-MonophosphateexperimentalunknownDetails
DB04503Sp-722experimentalunknownDetails
DB04530S,S-(2-Hydroxyethyl)ThiocysteineexperimentalunknownDetails
DB04586o-BromophenolexperimentalunknownDetails
DB046964-CHLORO-3',3''-DIBROMOPHENOL-1,8-NAPHTHALEINexperimentalunknownDetails
DB081312-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-3-METHYL-BUTYRIC ACIDexperimentalunknownDetails