KTHY_ECOLI
ID KTHY_ECOLI Reviewed; 213 AA.
AC P0A720; P37345;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Thymidylate kinase;
DE EC=2.7.4.9 {ECO:0000269|PubMed:8631667};
DE AltName: Full=Thymidine monophosphate kinase;
DE AltName: Full=dTMP kinase;
DE Short=TMPK;
GN Name=tmk; Synonyms=ycfG; OrderedLocusNames=b1098, JW1084;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], CATALYTIC ACTIVITY, AND FUNCTION.
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=8631667; DOI=10.1128/jb.178.10.2804-2812.1996;
RA Reynes J.-P., Tiraby M., Baron M., Drocourt D., Tiraby G.;
RT "Escherichia coli thymidylate kinase: molecular cloning, nucleotide
RT sequence, and genetic organization of the corresponding tmk locus.";
RL J. Bacteriol. 178:2804-2812(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=8905232; DOI=10.1093/dnares/3.3.137;
RA Oshima T., Aiba H., Baba T., Fujita K., Hayashi K., Honjo A., Ikemoto K.,
RA Inada T., Itoh T., Kajihara M., Kanai K., Kashimoto K., Kimura S.,
RA Kitagawa M., Makino K., Masuda S., Miki T., Mizobuchi K., Mori H.,
RA Motomura K., Nakamura Y., Nashimoto H., Nishio Y., Saito N., Sampei G.,
RA Seki Y., Tagami H., Takemoto K., Wada C., Yamamoto Y., Yano M.,
RA Horiuchi T.;
RT "A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT the 12.7-28.0 min region on the linkage map.";
RL DNA Res. 3:137-155(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 85-213.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=8509334; DOI=10.1128/jb.175.12.3812-3822.1993;
RA Carter J.R., Franden M.A., Aebersold R.H., McHenry C.S.;
RT "Identification, isolation, and characterization of the structural gene
RT encoding the delta' subunit of Escherichia coli DNA polymerase III
RT holoenzyme.";
RL J. Bacteriol. 175:3812-3822(1993).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 162-213.
RC STRAIN=K12;
RX PubMed=8505303; DOI=10.1016/s0021-9258(19)50264-2;
RA Dong Z., Onrust R., Skangalis M., O'Donnell M.;
RT "DNA polymerase III accessory proteins. I. holA and holB encoding delta and
RT delta'.";
RL J. Biol. Chem. 268:11758-11765(1993).
RN [7]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11369858; DOI=10.1110/ps.45701;
RA Munier-Lehmann H., Chaffotte A., Pochet S., Labesse G.;
RT "Thymidylate kinase of Mycobacterium tuberculosis: a chimera sharing
RT properties common to eukaryotic and bacterial enzymes.";
RL Protein Sci. 10:1195-1205(2001).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.98 ANGSTROMS) OF COMPLEXES WITH THE BISUBSTRATE
RP INHIBITORS TP5A AND AZT-P5A.
RX PubMed=9826650; DOI=10.1073/pnas.95.24.14045;
RA Lavie A., Ostermann N., Brundiers R., Goody R.S., Reinstein J., Konrad M.,
RA Schlichting I.;
RT "Structural basis for efficient phosphorylation of 3'-azidothymidine
RT monophosphate by Escherichia coli thymidylate kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:14045-14050(1998).
CC -!- FUNCTION: Catalyzes the reversible phosphorylation of deoxythymidine
CC monophosphate (dTMP) to deoxythymidine diphosphate (dTDP), using ATP as
CC its preferred phosphoryl donor (PubMed:8631667). Situated at the
CC junction of both de novo and salvage pathways of deoxythymidine
CC triphosphate (dTTP) synthesis, is essential for DNA synthesis and
CC cellular growth. {ECO:0000269|PubMed:8631667}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + dTMP = ADP + dTDP; Xref=Rhea:RHEA:13517,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58369, ChEBI:CHEBI:63528,
CC ChEBI:CHEBI:456216; EC=2.7.4.9;
CC Evidence={ECO:0000269|PubMed:8631667};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.04 mM for ATP (at pH 7.4 and 30 degrees Celsius)
CC {ECO:0000269|PubMed:11369858};
CC KM=15 uM for dTMP (at pH 7.4 and 30 degrees Celsius)
CC {ECO:0000269|PubMed:11369858};
CC Vmax=50 umol/min/mg enzyme with ATP and dTMP as substrates (at pH 7.4
CC and 30 degrees Celsius) {ECO:0000269|PubMed:11369858};
CC -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis.
CC -!- SUBUNIT: Homodimer.
CC -!- DOMAIN: The LID domain is a solvent-exposed domain that closes over the
CC site of phosphoryl transfer upon ATP binding.
CC -!- SIMILARITY: Belongs to the thymidylate kinase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=L01483; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U41456; AAB06878.1; -; Genomic_DNA.
DR EMBL; U00096; AAC74182.1; -; Genomic_DNA.
DR EMBL; AP009048; BAA35905.1; -; Genomic_DNA.
DR EMBL; L01483; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L04577; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; JC6006; G64853.
DR RefSeq; NP_415616.1; NC_000913.3.
DR RefSeq; WP_001257000.1; NZ_STEB01000016.1.
DR PDB; 1E9F; X-ray; 1.90 A; A=151-156.
DR PDB; 4TMK; X-ray; 1.98 A; A=1-213.
DR PDB; 5TMP; X-ray; 1.98 A; A=1-213.
DR PDBsum; 1E9F; -.
DR PDBsum; 4TMK; -.
DR PDBsum; 5TMP; -.
DR AlphaFoldDB; P0A720; -.
DR SMR; P0A720; -.
DR BioGRID; 4263411; 41.
DR DIP; DIP-48110N; -.
DR IntAct; P0A720; 8.
DR STRING; 511145.b1098; -.
DR ChEMBL; CHEMBL3309028; -.
DR jPOST; P0A720; -.
DR PaxDb; P0A720; -.
DR PRIDE; P0A720; -.
DR EnsemblBacteria; AAC74182; AAC74182; b1098.
DR EnsemblBacteria; BAA35905; BAA35905; BAA35905.
DR GeneID; 66670636; -.
DR GeneID; 945663; -.
DR KEGG; ecj:JW1084; -.
DR KEGG; eco:b1098; -.
DR PATRIC; fig|1411691.4.peg.1170; -.
DR EchoBASE; EB2208; -.
DR eggNOG; COG0125; Bacteria.
DR HOGENOM; CLU_049131_0_1_6; -.
DR InParanoid; P0A720; -.
DR OMA; VMTREPG; -.
DR PhylomeDB; P0A720; -.
DR BioCyc; EcoCyc:DTMPKI-MON; -.
DR BioCyc; MetaCyc:DTMPKI-MON; -.
DR SABIO-RK; P0A720; -.
DR UniPathway; UPA00575; -.
DR EvolutionaryTrace; P0A720; -.
DR PRO; PR:P0A720; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IDA:EcoliWiki.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004798; F:thymidylate kinase activity; IDA:EcoCyc.
DR GO; GO:0009041; F:uridylate kinase activity; IBA:GO_Central.
DR GO; GO:0006233; P:dTDP biosynthetic process; IDA:EcoliWiki.
DR GO; GO:0006235; P:dTTP biosynthetic process; IDA:EcoliWiki.
DR GO; GO:0006227; P:dUDP biosynthetic process; IBA:GO_Central.
DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; IDA:EcoliWiki.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_00165; Thymidylate_kinase; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR039430; Thymidylate_kin-like_dom.
DR InterPro; IPR018095; Thymidylate_kin_CS.
DR InterPro; IPR018094; Thymidylate_kinase.
DR Pfam; PF02223; Thymidylate_kin; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00041; DTMP_kinase; 1.
DR PROSITE; PS01331; THYMIDYLATE_KINASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Kinase; Nucleotide biosynthesis;
KW Nucleotide-binding; Reference proteome; Transferase.
FT CHAIN 1..213
FT /note="Thymidylate kinase"
FT /id="PRO_0000155269"
FT REGION 147..159
FT /note="LID"
FT BINDING 10..17
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 12
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT /evidence="ECO:0000269|PubMed:9826650"
FT BINDING 74
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT BINDING 78
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT BINDING 100
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT BINDING 105
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT BINDING 108
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT BINDING 109
FT /ligand="dTMP"
FT /ligand_id="ChEBI:CHEBI:63528"
FT SITE 153
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000269|PubMed:9826650"
FT CONFLICT 112
FT /note="G -> A (in Ref. 5)"
FT /evidence="ECO:0000305"
FT CONFLICT 122
FT /note="T -> N (in Ref. 5)"
FT /evidence="ECO:0000305"
FT STRAND 5..10
FT /evidence="ECO:0007829|PDB:4TMK"
FT HELIX 16..29
FT /evidence="ECO:0007829|PDB:4TMK"
FT STRAND 35..41
FT /evidence="ECO:0007829|PDB:4TMK"
FT HELIX 45..55
FT /evidence="ECO:0007829|PDB:4TMK"
FT TURN 57..62
FT /evidence="ECO:0007829|PDB:4TMK"
FT HELIX 67..84
FT /evidence="ECO:0007829|PDB:4TMK"
FT HELIX 86..91
FT /evidence="ECO:0007829|PDB:4TMK"
FT STRAND 95..99
FT /evidence="ECO:0007829|PDB:4TMK"
FT HELIX 102..108
FT /evidence="ECO:0007829|PDB:4TMK"
FT TURN 109..113
FT /evidence="ECO:0007829|PDB:4TMK"
FT HELIX 117..128
FT /evidence="ECO:0007829|PDB:4TMK"
FT STRAND 134..140
FT /evidence="ECO:0007829|PDB:4TMK"
FT HELIX 143..153
FT /evidence="ECO:0007829|PDB:4TMK"
FT TURN 158..161
FT /evidence="ECO:0007829|PDB:4TMK"
FT HELIX 164..179
FT /evidence="ECO:0007829|PDB:4TMK"
FT STRAND 184..188
FT /evidence="ECO:0007829|PDB:4TMK"
FT HELIX 193..209
FT /evidence="ECO:0007829|PDB:4TMK"
SQ SEQUENCE 213 AA; 23783 MW; 16BC0A725AAFCB72 CRC64;
MRSKYIVIEG LEGAGKTTAR NVVVETLEQL GIRDMVFTRE PGGTQLAEKL RSLVLDIKSV
GDEVITDKAE VLMFYAARVQ LVETVIKPAL ANGTWVIGDR HDLSTQAYQG GGRGIDQHML
ATLRDAVLGD FRPDLTLYLD VTPEVGLKRA RARGELDRIE QESFDFFNRT RARYLELAAQ
DKSIHTIDAT QPLEAVMDAI RTTVTHWVKE LDA
