Thymidylate synthase (P0A884)

Identification
Name:Thymidylate synthase
Synonyms:
  • TS
  • TSase
Gene Name:thyA
Enzyme Class:
Biological Properties
General Function:Involved in 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
Cellular Location:Cytoplasm
SMPDB Pathways:
KEGG Pathways:
KEGG Reactions:
1.0Thumb+1.0Thumb ↔ 1.0Thumb+1.0Thumb
1.0dUMP + 1.05,10-Methylene-THF ↔ 1.0Dihydrofolic acid + 1.05-Thymidylic acid
ReactionCard
SMPDB Reactions:
1.0Thumb+1.0Thumb+1.0Dihydrofolic acid → 1.05,10-Methylene-THF+1.0Thumb+1.0Thumb
1.0Dihydrofolic acid + 1.05-Thymidylic acid + 1.0Dihydrofolic acid → 1.05,10-Methylene-THF + 1.0dUMP + 1.05,10-Methylene-THF
ReactionCard
1.0Thumb+1.05,10-methenyltetrahydrofolate mono-L-glutamate+1.05,10-methenyltetrahydrofolate mono-L-glutamate → 1.0Thumb+1.0Thumb+1.0Dihydrofolic acid
1.0dUMP + 1.05,10-methenyltetrahydrofolate mono-L-glutamate + 1.05,10-methenyltetrahydrofolate mono-L-glutamate → 1.0Dihydrofolic acid + 1.05-Thymidylic acid + 1.0Dihydrofolic acid
ReactionCard
EcoCyc Reactions:
1.0Thumb+1.0Thumb ↔ 1.0Thumb+1.0Thumb
1.0dUMP + 1.05,10-Methylene-THF ↔ 1.0Dihydrofolic acid + 1.05-Thymidylic acid
ReactionCard
Metabolites:
ECMDB IDNameView
ECMDB013545,10-Methylene-THFMetaboCard
ECMDB012275-Thymidylic acidMetaboCard
ECMDB01056Dihydrofolic acidMetaboCard
ECMDB01409dUMPMetaboCard
GO Classification:
Function
5,10-methylenetetrahydrofolate-dependent methyltransferase activity
catalytic activity
methyltransferase activity
thymidylate synthase activity
transferase activity
transferase activity, transferring one-carbon groups
Process
cellular nitrogen compound metabolic process
dTMP biosynthetic process
metabolic process
nitrogen compound metabolic process
nucleobase, nucleoside and nucleotide metabolic process
nucleobase, nucleoside, nucleotide and nucleic acid metabolic process
nucleoside phosphate metabolic process
nucleotide metabolic process
pyrimidine deoxyribonucleoside monophosphate biosynthetic process
pyrimidine nucleoside monophosphate biosynthetic process
pyrimidine nucleotide biosynthetic process
pyrimidine nucleotide metabolic process
Gene Properties
Blattner:b2827
Gene OrientationCounterclockwise
Centisome Percentage:63.85
Left Sequence End2962383
Right Sequence End2963177
Gene Sequence:
>795 bp
ATGCACTCTGAACGCGCACCGTTTTTCCTCAAACTGGCGGCCTGGGGCGGCGTTGTTTTC
CTACATTTTCCCATCCTGATAATCGCCGCCTATGCGTTTAACACTGAAGATGCGGCGTTT
AGTTTTCCACCGCAGGGCCTGACGCTGCGCTGGTTTAGCGTGGCAGCACAGCGTAGTGAT
ATTCTTGATGCCGTGACACTGTCACTTAAAGTGGCGGCGCTGGCGACATTAATTGCGCTG
GTGTTAGGGACGCTGGCAGCTGCCGCGCTGTGGCGACGAGACTTTTTCGGCAAAAACGCC
ATTTCGCTGTTACTGCTGCTGCCCATTGCGCTGCCGGGCATTGTCACTGGTCTGGCGTTA
TTAACCGCCTTTAAAACCATCAATCTGGAGCCGGGATTTTTCACCATCGTGGTCGGTCAT
GCGACTTTTTGTGTAGTTGTGGTGTTTAACAATGTCATCGCCCGTTTTCGCCGCACCTCC
TGGAGTCTGGTTGAGGCGTCAATGGATCTTGGGGCCAATGGCTGGCAAACCTTCCGCTAC
GTAGTGTTGCCGAATCTCAGTTCGGCGTTACTGGCAGGAGGAATGCTGGCGTTTGCCTTG
TCGTTCGATGAAATCATCGTTACGACCTTTACGGCAGGTCATGAACGAACGTTACCGTTG
TGGTTGCTCAATCAGCTTGGGCGACCGCGTGATGTACCGGTAACTAACGTGGTGGCACTG
CTGGTTATGTTGGTAACAACCTTGCCGATCCTGGGGGCCTGGTGGCTAACCCGCGAAGGC
GACAATGGTCAATAA
Protein Properties
Pfam Domain Function:
Protein Residues:264
Protein Molecular Weight:30480
Protein Theoretical pI:6
PDB File:2KCE
Signaling Regions:
  • None
Transmembrane Regions:
  • None
Protein Sequence:
>Thymidylate synthase
MKQYLELMQKVLDEGTQKNDRTGTGTLSIFGHQMRFNLQDGFPLVTTKRCHLRSIIHELL
WFLQGDTNIAYLHENNVTIWDEWADENGDLGPVYGKQWRAWPTPDGRHIDQITTVLNQLK
NDPDSRRIIVSAWNVGELDKMALAPCHAFFQFYVADGKLSCQLYQRSCDVFLGLPFNIAS
YALLVHMMAQQCDLEVGDFVWTGGDTHLYSNHMDQTHLQLSREPRPLPKLIIKRKPESIF
DYRFEDFEIEGYDPHPGIKAPVAI
References
External Links:
ResourceLink
Uniprot ID:P0A884
Uniprot Name:TYSY_ECOLI
GenBank Gene ID:AP009048
Genebank Protein ID:1742351
PDB ID:2KCE
Ecogene ID:EG11002
Ecocyc:EG11002
ColiBase:b2827
Kegg Gene:b2827
EchoBASE ID:EB0995
CCDB:TYSY_ECOLI
BacMap:16130731
General Reference:
  • Belfort, M., Maley, G., Pedersen-Lane, J., Maley, F. (1983). "Primary structure of the Escherichia coli thyA gene and its thymidylate synthase product." Proc Natl Acad Sci U S A 80:4914-4918. Pubmed: 6308660
  • Blattner, F. R., Plunkett, G. 3rd, Bloch, C. A., Perna, N. T., Burland, V., Riley, M., Collado-Vides, J., Glasner, J. D., Rode, C. K., Mayhew, G. F., Gregor, J., Davis, N. W., Kirkpatrick, H. A., Goeden, M. A., Rose, D. J., Mau, B., Shao, Y. (1997). "The complete genome sequence of Escherichia coli K-12." Science 277:1453-1462. Pubmed: 9278503
  • Erlanson, D. A., Braisted, A. C., Raphael, D. R., Randal, M., Stroud, R. M., Gordon, E. M., Wells, J. A. (2000). "Site-directed ligand discovery." Proc Natl Acad Sci U S A 97:9367-9372. Pubmed: 10944209
  • Fauman, E. B., Rutenber, E. E., Maley, G. F., Maley, F., Stroud, R. M. (1994). "Water-mediated substrate/product discrimination: the product complex of thymidylate synthase at 1.83 A." Biochemistry 33:1502-1511. Pubmed: 8312270
  • Finch, P. W., Wilson, R. E., Brown, K., Hickson, I. D., Tomkinson, A. E., Emmerson, P. T. (1986). "Complete nucleotide sequence of the Escherichia coli recC gene and of the thyA-recC intergenic region." Nucleic Acids Res 14:4437-4451. Pubmed: 3520484
  • Hayashi, K., Morooka, N., Yamamoto, Y., Fujita, K., Isono, K., Choi, S., Ohtsubo, E., Baba, T., Wanner, B. L., Mori, H., Horiuchi, T. (2006). "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Mol Syst Biol 2:2006.0007. Pubmed: 16738553
  • Kim, C. W., Michaels, M. L., Miller, J. H. (1992). "Amino acid substitution analysis of E. coli thymidylate synthase: the study of a highly conserved region at the N-terminus." Proteins 13:352-363. Pubmed: 1518803
  • Montfort, W. R., Perry, K. M., Fauman, E. B., Finer-Moore, J. S., Maley, G. F., Hardy, L., Maley, F., Stroud, R. M. (1990). "Structure, multiple site binding, and segmental accommodation in thymidylate synthase on binding dUMP and an anti-folate." Biochemistry 29:6964-6977. Pubmed: 2223754
  • Perry, K. M., Fauman, E. B., Finer-Moore, J. S., Montfort, W. R., Maley, G. F., Maley, F., Stroud, R. M. (1990). "Plastic adaptation toward mutations in proteins: structural comparison of thymidylate synthases." Proteins 8:315-333. Pubmed: 2128651
  • Reyes, C. L., Sage, C. R., Rutenber, E. E., Nissen, R. M., Finer-Moore, J. S., Stroud, R. M. (1998). "Inactivity of N229A thymidylate synthase due to water-mediated effects: isolating a late stage in methyl transfer." J Mol Biol 284:699-712. Pubmed: 9826509
  • Sage, C. R., Rutenber, E. E., Stout, T. J., Stroud, R. M. (1996). "An essential role for water in an enzyme reaction mechanism: the crystal structure of the thymidylate synthase mutant E58Q." Biochemistry 35:16270-16281. Pubmed: 8973201
  • Strop, P., Changchien, L., Maley, F., Montfort, W. R. (1997). "Crystal structures of a marginally active thymidylate synthase mutant, Arg 126-->Glu." Protein Sci 6:2504-2511. Pubmed: 9416600
  • Voeller, D. M., Changchien, L. M., Maley, G. F., Maley, F., Takechi, T., Turner, R. E., Montfort, W. R., Allegra, C. J., Chu, E. (1995). "Characterization of a specific interaction between Escherichia coli thymidylate synthase and Escherichia coli thymidylate synthase mRNA." Nucleic Acids Res 23:869-875. Pubmed: 7708505