Thymidylate kinase

Details

Name
Thymidylate kinase
Synonyms
  • 2.7.4.9
  • dTMP kinase
  • Thymidine monophosphate kinase
  • TMPK
Gene Name
tmk
Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Amino acid sequence
>lcl|BSEQ0051201|Thymidylate kinase
MLIAIEGVDGAGKRTLVEKLSGAFRAAGRSVATLAFPRYGQSVAADIAAEALHGEHGDLA
SSVYAMATLFALDRAGAVHTIQGLCRGYDVVILDRYVASNAAYSAARLHENAAGKAAAWV
QRIEFARLGLPKPDWQVLLAVSAELAGERSRGRAQRDPGRARDNYERDAELQQRTGAVYA
ELAAQGWGGRWLVVGADVDPGRLAATLAPPDVPS
Number of residues
214
Molecular Weight
22634.285
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / GTP binding / magnesium ion binding / protein homodimerization activity / thymidylate kinase activity / uridylate kinase activity
Processes
dTDP biosynthetic process / dTTP biosynthetic process / dUDP biosynthetic process / TMP metabolic process
Components
cytoplasm
General Function
Catalyzes the reversible phosphorylation of deoxythymidine monophosphate (dTMP) to deoxythymidine diphosphate (dTDP), using ATP as its preferred phosphoryl donor. Situated at the junction of both de novo and salvage pathways of deoxythymidine triphosphate (dTTP) synthesis, is essential for DNA synthesis and cellular growth. Has a broad specificity for nucleoside triphosphates, being highly active with ATP or dATP as phosphate donors, and less active with ITP, GTP, CTP and UTP.
Specific Function
Atp binding
Pfam Domain Function
Not Available
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0051202|Thymidylate kinase (tmk)
GTGCTAATCGCGATTGAGGGCGTTGACGGCGCTGGCAAGCGGACGTTGGTGGAAAAGCTG
TCCGGGGCCTTTCGAGCAGCCGGGAGATCGGTGGCCACACTGGCGTTCCCGCGCTACGGA
CAGTCGGTGGCCGCCGACATCGCAGCGGAGGCGCTGCACGGCGAGCACGGTGACCTCGCA
TCGTCGGTGTATGCGATGGCGACGCTGTTCGCGCTCGACCGCGCTGGCGCGGTCCACACG
ATCCAGGGGCTGTGTCGCGGCTACGACGTGGTGATCCTGGATCGCTACGTCGCCTCCAAC
GCGGCCTACAGCGCGGCGCGCCTACATGAAAACGCGGCCGGGAAGGCAGCGGCCTGGGTT
CAGCGGATCGAATTTGCAAGACTCGGGTTGCCCAAGCCCGACTGGCAGGTGCTCCTTGCG
GTCTCTGCCGAGCTCGCCGGGGAACGATCCCGCGGCCGTGCCCAGCGTGACCCCGGTCGG
GCGCGCGACAATTACGAACGCGACGCTGAACTTCAGCAGCGCACCGGTGCGGTCTACGCC
GAGTTGGCGGCCCAAGGGTGGGGCGGCCGGTGGCTGGTTGTCGGCGCCGATGTTGATCCG
GGCCGACTAGCGGCGACTTTGGCGCCTCCAGACGTGCCAAGTTGA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP9WKE1
UniProtKB Entry NameKTHY_MYCTU
General References
  1. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG: Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998 Jun 11;393(6685):537-44. [PubMed:9634230]
  2. Munier-Lehmann H, Chaffotte A, Pochet S, Labesse G: Thymidylate kinase of Mycobacterium tuberculosis: a chimera sharing properties common to eukaryotic and bacterial enzymes. Protein Sci. 2001 Jun;10(6):1195-205. [PubMed:11369858]
  3. Li de la Sierra I, Munier-Lehmann H, Gilles AM, Barzu O, Delarue M: Crystallization and preliminary X-ray analysis of the thymidylate kinase from Mycobacterium tuberculosis. Acta Crystallogr D Biol Crystallogr. 2000 Feb;56(Pt 2):226-8. [PubMed:10666613]
  4. Raman K, Yeturu K, Chandra N: targetTB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis. BMC Syst Biol. 2008 Dec 19;2:109. doi: 10.1186/1752-0509-2-109. [PubMed:19099550]
  5. Kelkar DS, Kumar D, Kumar P, Balakrishnan L, Muthusamy B, Yadav AK, Shrivastava P, Marimuthu A, Anand S, Sundaram H, Kingsbury R, Harsha HC, Nair B, Prasad TS, Chauhan DS, Katoch K, Katoch VM, Kumar P, Chaerkady R, Ramachandran S, Dash D, Pandey A: Proteogenomic analysis of Mycobacterium tuberculosis by high resolution mass spectrometry. Mol Cell Proteomics. 2011 Dec;10(12):M111.011627. doi: 10.1074/mcp.M111.011445. Epub 2011 Oct 3. [PubMed:21969609]
  6. Li de la Sierra I, Munier-Lehmann H, Gilles AM, Barzu O, Delarue M: X-ray structure of TMP kinase from Mycobacterium tuberculosis complexed with TMP at 1.95 A resolution. J Mol Biol. 2001 Aug 3;311(1):87-100. [PubMed:11469859]
  7. Ursby T, Weik M, Fioravanti E, Delarue M, Goeldner M, Bourgeois D: Cryophotolysis of caged compounds: a technique for trapping intermediate states in protein crystals. Acta Crystallogr D Biol Crystallogr. 2002 Apr;58(Pt 4):607-14. Epub 2002 Mar 22. [PubMed:11914484]
  8. Haouz A, Vanheusden V, Munier-Lehmann H, Froeyen M, Herdewijn P, Van Calenbergh S, Delarue M: Enzymatic and structural analysis of inhibitors designed against Mycobacterium tuberculosis thymidylate kinase. New insights into the phosphoryl transfer mechanism. J Biol Chem. 2003 Feb 14;278(7):4963-71. Epub 2002 Nov 25. [PubMed:12454011]
  9. Fioravanti E, Haouz A, Ursby T, Munier-Lehmann H, Delarue M, Bourgeois D: Mycobacterium tuberculosis thymidylate kinase: structural studies of intermediates along the reaction pathway. J Mol Biol. 2003 Apr 11;327(5):1077-92. [PubMed:12662932]
  10. Fioravanti E, Adam V, Munier-Lehmann H, Bourgeois D: The crystal structure of Mycobacterium tuberculosis thymidylate kinase in complex with 3'-azidodeoxythymidine monophosphate suggests a mechanism for competitive inhibition. Biochemistry. 2005 Jan 11;44(1):130-7. [PubMed:15628853]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01643Thymidine monophosphateexperimentalunknownDetails
DB02452Thymidine-5'-TriphosphateexperimentalunknownDetails
DB03280P1-(5'-Adenosyl)P5-(5'-Thymidyl)PentaphosphateexperimentalunknownDetails
DB036663'-Azido-3'-Deoxythymidine-5'-MonophosphateexperimentalunknownDetails
DB038465-Hydroxymethyluridine-2'-Deoxy-5'-MonophosphateexperimentalunknownDetails
DB04160Pyrophosphoric acidapproved, experimentalunknownDetails
DB04485Thymidineexperimental, investigationalunknownDetails