Gene - combatTB X

tmk

Type: protein_coding
Name: tmk
Locus Name: Rv3247c
Product: Thymidylate kinase Tmk (dTMP kinase) (thymidylic acid kinase) (TMPK)
Functional Category: Intermediary metabolism and respiration
Location: 3627419..3628063 (- strand)
Gene Length: 644 bp
Nucleotides: GTGCTAATCGCGATTGAGGGCGTTGACGGCGCTGGCAAGCGGACGTTGGTGGAAAAGCTGTCCGGGGCCTTTCGAGCAGCCGGGAGATCGGTGGCCACACTGGCGTTCCCGCGCTACGGACAGTCGGTGGCCGCCGACATCGCAGCGGAGGCGCTGCACGGCGAGCACGGTGACCTCGCATCGTCGGTGTATGCGATGGCGACGCTGTTCGCGCTCGACCGCGCTGGCGCGGTCCACACGATCCAGGGGCTGTGTCGCGGCTACGACGTGGTGATCCTGGATCGCTACGTCGCCTCCAACGCGGCCTACAGCGCGGCGCGCCTACATGAAAACGCGGCCGGGAAGGCAGCGGCCTGGGTTCAGCGGATCGAATTTGCAAGACTCGGGTTGCCCAAGCCCGACTGGCAGGTGCTCCTTGCGGTCTCTGCCGAGCTCGCCGGGGAACGATCCCGCGGCCGTGCCCAGCGTGACCCCGGTCGGGCGCGCGACAATTACGAACGCGACGCTGAACTTCAGCAGCGCACCGGTGCGGTCTACGCCGAGTTGGCGGCCCAAGGGTGGGGCGGCCGGTGGCTGGTTGTCGGCGCCGATGTTGATCCGGGCCGACTAGCGGCGACTTTGGCGCCTCCAGACGTGCCAAGTTG
Drug Resistance: Check for drug resistance association at TBDREAMDB
Mutations: Check for mutants available at TARGET

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.

Family

Thymidylate kinase family

GO

magnesium ion binding GO:0000287 molecular_function
uridylate kinase activity GO:0009041 molecular_function
TMP metabolic process GO:0046044 biological_process
ATP binding GO:0005524 molecular_function
GTP binding GO:0005525 molecular_function
thymidylate kinase activity GO:0004798 molecular_function
dUDP biosynthetic process GO:0006227 biological_process
dTDP biosynthetic process GO:0006233 biological_process
dTTP biosynthetic process GO:0006235 biological_process
cytoplasm GO:0005737 cellular_component
protein homodimerization activity GO:0042803 molecular_function
cytosol GO:0005829 cellular_component

InterPro

UniProt: P9WKE1
GenBank: Rv3247c
EnsemblBacteria: Rv3247c
Mycobrowser: Rv3247c

PDB IDs:

Summary

Name: Thymidylate kinase (EC 2.7.4.9) (Thymidine monophosphate kinase) (dTMP kinase) (TMPK)
Family: Thymidylate kinase family
Protein Sequence: MLIAIEGVDGAGKRTLVEKLSGAFRAAGRSVATLAFPRYGQSVAADIAAEALHGEHGDLASSVYAMATLFALDRAGAVHTIQGLCRGYDVVILDRYVASNAAYSAARLHENAAGKAAAWVQRIEFARLGLPKPDWQVLLAVSAELAGERSRGRAQRDPGRARDNYERDAELQQRTGAVYAELAAQGWGGRWLVVGADVDPGRLAATLAPPDVPS
Mass: 22,635 Da
Length: 214 Aa

Pyrophosphoric acid DB04160: acide diphosphorique | Diphosphoric acid | Diphosphorsäure | Pyrophosphorsäure

Rv3247c doesn't seem to be involved in any pathway.

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. doi: 10.1021/bi0484163.
Mycobacterium tuberculosis thymidylate kinase: structural studies of intermediates along the reaction pathway.: J Mol Biol. 2003 Apr 11;327(5):1077-92.
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. doi: 10.1074/jbc.M209630200. Epub 2002 Nov 25.
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. doi: 10.1107/s0907444902002135. Epub 2002 Mar 22.
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. doi: 10.1006/jmbi.2001.4843.
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.
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.
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. doi: 10.1107/s0907444999016212.
Thymidylate kinase of Mycobacterium tuberculosis: a chimera sharing properties common to eukaryotic and bacterial enzymes.: Protein Sci. 2001 Jun;10(6):1195-205. doi: 10.1110/ps.45701.
Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.: Nature. 1998 Jun 11;393(6685):537-44. doi: 10.1038/31159.