Thymidylate synthase

Details

Name
Thymidylate synthase
Kind
protein
Synonyms
  • 2.1.1.45
  • TS
Gene Name
thyA
UniProtKB Entry
P00469Swiss-Prot
Organism
Lactobacillus casei
NCBI Taxonomy ID
1582
Amino acid sequence
>lcl|BSEQ0002980|Thymidylate synthase
MLEQPYLDLAKKVLDEGHFKPDRTHTGTYSIFGHQMRFDLSKGFPLLTTKKVPFGLIKSE
LLWFLHGDTNIRFLLQHRNHIWDEWAFEKWVKSDEYHGPDMTDFGHRSQKDPEFAAVYHE
EMAKFDDRVLHDDAFAAKYGDLGLVYGSQWRAWHTSKGDTIDQLGDVIEQIKTHPYSRRL
IVSAWNPEDVPTMALPPCHTLYQFYVNDGKLSLQLYQRSADIFLGVPFNIASYALLTHLV
AHECGLEVGEFIHTFGDAHLYVNHLDQIKEQLSRTPRPAPTLQLNPDKHDIFDFDMKDIK
LLNYDPYPAIKAPVAV
Number of residues
316
Molecular Weight
36579.235
Theoretical pI
6.28
GO Classification
Functions
thymidylate synthase activity
Processes
dTMP biosynthetic process / dTTP biosynthetic process
Components
cytoplasm
General 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.
Specific Function
thymidylate synthase activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0002979|990 bp
ATGTGTCGAGTAGTGAACGGTAAAGGAGCAGAGCAGACAATGTTAGAACAGCCATATCTT
GATCTTGCAAAAAAAGTTCTGGATGAAGGCCATTTCAAGCCTGATCGGACCCATACAGGA
ACTTACAGTATTTTCGGCCACCAAATGCGTTTCGACCTTAGCAAGGGCTTTCCATTACTG
ACGACCAAAAAAGTACCATTCGGCCTTATTAAGAGTGAGTTGTTGTGGTTTTTACACGGT
GATACCAACATTCGGTTCTTACTCCAACACAGGAATCACATTTGGGATGAGTGGGCGTTT
GAAAAATGGGTGAAGAGTGATGAATATCACGGCCCGGACATGACTGATTTTGGGCATCGC
AGCCAAAAGGATCCGGAATTCGCGGCAGTTTATCATGAAGAAATGGCTAAATTCGATGAC
CGGGTGCTTCATGATGATGCTTTTGCAGCCAAATATGGTGATCTTGGCTTGGTTTATGGA
TCCCAATGGCGGGCCTGGCATACGAGCAAGGGTGACACGATCGACCAGTTGGGGGACGTT
ATTGAGCAAATCAAAACGCATCCCTATTCACGACGGCTCATCGTGTCGGCGTGGAATCCG
GAAGATGTCCCGACAATGGCGCTACCGCCTTGTCACACGCTCTATCAGTTTTATGTCAAT
GATGGCAAGCTGTCTTTGCAGTTGTACCAACGTTCGGCTGACATTTTTCTTGGCGTCCCG
TTTAATATCGCGTCCTATGCGTTGTTAACGCATCTGGTCGCGCATGAATGTGGCCTTGAA
GTTGGCGAATTCATTCATACATTCGGCGATGCGCATCTTTACGTCAATCATCTTGACCAA
ATTAAAGAGCAGCTCAGTCGCACGCCGCGGCCGGCACCGACTTTACAGTTGAATCCGGAT
AAACATGATATTTTCGACTTTGACATGAAGGATATTAAGTTGCTTAATTACGATCCTTAT
CCGGCCATTAAGGCACCGGTTGCCGTTTAA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP00469
UniProtKB Entry NameTYSY_LACCA
GenBank Protein ID149601
GenBank Gene IDM19653
PDB ID(s)1BO7, 1BO8, 1BP0, 1BP6, 1BPJ, 1JMF, 1JMG, 1JMH, 1JMI, 1LCA, 1LCB, 1LCE, 1NJA, 1NJB, 1NJC, 1NJD, 1NJE, 1TDA, 1TDB, 1TDC, 1THY, 1TSL, 1TSM, 1TSV, 1TSW, 1TSX, 1TSY, 1TSZ, 1TVU, 1TVV, 1TVW, 1VZA, 1VZB, 1VZC, 1VZD, 1VZE, 2G86, 2G89, 2G8A, 2G8D, 2TDD, 2TDM, 3BNZ, 3BYX, 3BZ0, 3C06, 3C0A, 3IJZ, 3IK0, 3IK1, 4TMS
General References
  1. Pinter K, Davisson VJ, Santi DV: Cloning, sequencing, and expression of the Lactobacillus casei thymidylate synthase gene. DNA. 1988 May;7(4):235-41. [Article]
  2. Maley GF, Bellisario RL, Guarino DU, Maley F: The primary structure of Lactobacillus casei thymidylate synthetase. III. The use of 2-(2-nitrophenylsulfenyl)-3-methyl-3-bromoindolenine and limited tryptic peptides to establish the complete amino acid sequence of the enzyme. J Biol Chem. 1979 Feb 25;254(4):1301-4. [Article]
  3. 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. [Article]
  4. Finer-Moore J, Fauman EB, Foster PG, Perry KM, Santi DV, Stroud RM: Refined structures of substrate-bound and phosphate-bound thymidylate synthase from Lactobacillus casei. J Mol Biol. 1993 Aug 20;232(4):1101-16. [Article]
  5. Kealey JT, Eckstein J, Santi DV: Role of the conserved tryptophan 82 of Lactobacillus casei thymidylate synthase. Chem Biol. 1995 Sep;2(9):609-14. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
5,10-Methylene-6-Hydrofolic AcidexperimentalunknowntargetDetails
10-Propargyl-5,8-Dideazafolic AcidexperimentalunknowntargetDetails
Uridine monophosphateexperimentalunknowntargetDetails
5-fluoro-2'-deoxyuridine-5'-monophosphateexperimentalunknowntargetDetails
2'-Deoxycytidine-5'-MonophosphateexperimentalunknowntargetDetails
Deoxyuridine monophosphateexperimentalunknowntargetDetails
Thymidine monophosphateexperimentalunknowntargetproduct ofDetails
2-(2-chloropyridin-4-yl)-4-methyl-1H-isoindole-1,3(2H)-dioneexperimentalunknowntargetDetails
2-(4-hydroxybiphenyl-3-yl)-4-methyl-1H-isoindole-1,3(2H)-dioneexperimentalunknowntargetDetails
4-(4-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)benzonitrileexperimentalunknowntargetDetails
3-DIPHENOL-6-NITRO-3H-BENZO[DE]ISOCHROMEN-1-ONEexperimentalunknowntargetDetails