MV3K_THEAC
ID MV3K_THEAC Reviewed; 318 AA.
AC Q9HIN1;
DT 26-NOV-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Mevalonate 3-kinase {ECO:0000303|PubMed:24914732};
DE Short=M3K {ECO:0000303|PubMed:24914732};
DE EC=2.7.1.185 {ECO:0000269|PubMed:24755225, ECO:0000269|PubMed:24914732};
DE AltName: Full=ATP:(R)-mevalonate 3-phosphotransferase {ECO:0000303|PubMed:24755225};
DE Short=ATP:(R)-MVA 3 phosphotransferase {ECO:0000303|PubMed:24755225};
GN OrderedLocusNames=Ta1305 {ECO:0000312|EMBL:CAC12426.1};
OS Thermoplasma acidophilum (strain ATCC 25905 / DSM 1728 / JCM 9062 / NBRC
OS 15155 / AMRC-C165).
OC Archaea; Candidatus Thermoplasmatota; Thermoplasmata; Thermoplasmatales;
OC Thermoplasmataceae; Thermoplasma.
OX NCBI_TaxID=273075;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25905 / DSM 1728 / JCM 9062 / NBRC 15155 / AMRC-C165;
RX PubMed=11029001; DOI=10.1038/35035069;
RA Ruepp A., Graml W., Santos-Martinez M.-L., Koretke K.K., Volker C.,
RA Mewes H.-W., Frishman D., Stocker S., Lupas A.N., Baumeister W.;
RT "The genome sequence of the thermoacidophilic scavenger Thermoplasma
RT acidophilum.";
RL Nature 407:508-513(2000).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RC STRAIN=ATCC 25905 / DSM 1728 / JCM 9062 / NBRC 15155 / AMRC-C165;
RX PubMed=24914732; DOI=10.1021/bi500566q;
RA Vinokur J.M., Korman T.P., Cao Z., Bowie J.U.;
RT "Evidence of a novel mevalonate pathway in archaea.";
RL Biochemistry 53:4161-4168(2014).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=24755225; DOI=10.1074/jbc.m114.562686;
RA Azami Y., Hattori A., Nishimura H., Kawaide H., Yoshimura T., Hemmi H.;
RT "(R)-mevalonate 3-phosphate is an intermediate of the mevalonate pathway in
RT Thermoplasma acidophilum.";
RL J. Biol. Chem. 289:15957-15967(2014).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND ATP
RP ANALOG, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF LEU-18; SER-105 AND
RP ARG-185, AND SUBUNIT.
RX PubMed=25422158; DOI=10.1002/pro.2607;
RA Vinokur J.M., Korman T.P., Sawaya M.R., Collazo M., Cascio D., Bowie J.U.;
RT "Structural analysis of mevalonate-3-kinase provides insight into the
RT mechanisms of isoprenoid pathway decarboxylases.";
RL Protein Sci. 24:212-220(2015).
CC -!- FUNCTION: Catalyzes the phosphorylation of mevalonate (MVA) to yield
CC mevalonate-3-phosphate. Functions in an alternative mevalonate pathway,
CC only present in extreme acidophiles of the Thermoplasmatales order,
CC which passes through mevalonate 3-phosphate rather than mevalonate 5-
CC phosphate. {ECO:0000269|PubMed:24755225, ECO:0000269|PubMed:24914732}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-mevalonate + ATP = (R)-3-phosphomevalonate + ADP + H(+);
CC Xref=Rhea:RHEA:42884, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:36464, ChEBI:CHEBI:82773, ChEBI:CHEBI:456216;
CC EC=2.7.1.185; Evidence={ECO:0000269|PubMed:24755225,
CC ECO:0000269|PubMed:24914732};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=97 uM for (R)-mevalonate {ECO:0000269|PubMed:24914732};
CC KM=130 uM for ATP {ECO:0000269|PubMed:25422158};
CC Note=kcat is 5.3 sec(-1) for ATP as substrate (PubMed:25422158). kcat
CC is 5 sec(-1) for (R)-mevalonate as substrate (PubMed:24914732).
CC {ECO:0000269|PubMed:24914732, ECO:0000269|PubMed:25422158};
CC pH dependence:
CC Optimum pH is 8.5. {ECO:0000269|PubMed:24914732};
CC Temperature dependence:
CC Optimum temperature is 55 degrees Celsius.
CC {ECO:0000269|PubMed:24914732};
CC -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC via mevalonate pathway. {ECO:0000269|PubMed:24755225,
CC ECO:0000269|PubMed:24914732}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:25422158}.
CC -!- SIMILARITY: Belongs to the GHMP kinase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL445067; CAC12426.1; -; Genomic_DNA.
DR RefSeq; WP_010901711.1; NC_002578.1.
DR PDB; 4RKP; X-ray; 2.10 A; A/B=1-318.
DR PDB; 4RKS; X-ray; 2.00 A; A/B=1-318.
DR PDB; 4RKZ; X-ray; 2.30 A; A/B=1-318.
DR PDBsum; 4RKP; -.
DR PDBsum; 4RKS; -.
DR PDBsum; 4RKZ; -.
DR AlphaFoldDB; Q9HIN1; -.
DR SMR; Q9HIN1; -.
DR STRING; 273075.Ta1305; -.
DR EnsemblBacteria; CAC12426; CAC12426; CAC12426.
DR GeneID; 1456782; -.
DR KEGG; tac:Ta1305; -.
DR eggNOG; arCOG02937; Archaea.
DR HOGENOM; CLU_862228_0_0_2; -.
DR OMA; WNSYIVT; -.
DR OrthoDB; 77836at2157; -.
DR BioCyc; MetaCyc:MON-18735; -.
DR BRENDA; 2.7.1.185; 6324.
DR UniPathway; UPA00057; -.
DR Proteomes; UP000001024; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0016773; F:phosphotransferase activity, alcohol group as acceptor; IDA:UniProtKB.
DR GO; GO:0019287; P:isopentenyl diphosphate biosynthetic process, mevalonate pathway; IDA:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR Gene3D; 3.30.230.10; -; 1.
DR Gene3D; 3.30.70.890; -; 1.
DR InterPro; IPR036554; GHMP_kinase_C_sf.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR InterPro; IPR014721; Ribosomal_S5_D2-typ_fold_subgr.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55060; SSF55060; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Isoprene biosynthesis; Kinase;
KW Lipid biosynthesis; Lipid metabolism; Nucleotide-binding;
KW Reference proteome; Transferase.
FT CHAIN 1..318
FT /note="Mevalonate 3-kinase"
FT /id="PRO_0000431278"
FT BINDING 19
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:25422158,
FT ECO:0007744|PDB:4RKS"
FT BINDING 96..100
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:25422158,
FT ECO:0007744|PDB:4RKZ"
FT BINDING 105..108
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:25422158,
FT ECO:0007744|PDB:4RKP, ECO:0007744|PDB:4RKZ"
FT BINDING 140
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:25422158,
FT ECO:0007744|PDB:4RKS"
FT BINDING 144
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:25422158,
FT ECO:0007744|PDB:4RKS"
FT BINDING 185
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:25422158,
FT ECO:0007744|PDB:4RKZ"
FT BINDING 188
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:25422158,
FT ECO:0007744|PDB:4RKP, ECO:0007744|PDB:4RKZ"
FT MUTAGEN 18
FT /note="L->A: Strong decrease of the affinity for ATP, but
FT almost the same catalytic efficiency compared to the wild-
FT type."
FT /evidence="ECO:0000269|PubMed:25422158"
FT MUTAGEN 105
FT /note="S->A: 4.6-fold decrease in the catalytic efficiency
FT for ATP, with only a marginal decrease in affinity compared
FT to the wild-type."
FT /evidence="ECO:0000269|PubMed:25422158"
FT MUTAGEN 185
FT /note="R->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:25422158"
FT MUTAGEN 185
FT /note="R->K: Strong decrease of the affinity for ATP and
FT 17-fold decrease of the catalytic efficiency compared to
FT the wild-type."
FT /evidence="ECO:0000269|PubMed:25422158"
FT STRAND 4..10
FT /evidence="ECO:0007829|PDB:4RKS"
FT STRAND 13..17
FT /evidence="ECO:0007829|PDB:4RKS"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:4RKS"
FT STRAND 30..32
FT /evidence="ECO:0007829|PDB:4RKS"
FT STRAND 34..40
FT /evidence="ECO:0007829|PDB:4RKS"
FT STRAND 46..54
FT /evidence="ECO:0007829|PDB:4RKS"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:4RKS"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:4RKS"
FT HELIX 73..80
FT /evidence="ECO:0007829|PDB:4RKS"
FT HELIX 82..89
FT /evidence="ECO:0007829|PDB:4RKS"
FT STRAND 94..103
FT /evidence="ECO:0007829|PDB:4RKS"
FT HELIX 109..122
FT /evidence="ECO:0007829|PDB:4RKS"
FT HELIX 128..135
FT /evidence="ECO:0007829|PDB:4RKS"
FT TURN 136..138
FT /evidence="ECO:0007829|PDB:4RKS"
FT HELIX 142..147
FT /evidence="ECO:0007829|PDB:4RKS"
FT STRAND 148..155
FT /evidence="ECO:0007829|PDB:4RKS"
FT STRAND 160..166
FT /evidence="ECO:0007829|PDB:4RKS"
FT HELIX 168..171
FT /evidence="ECO:0007829|PDB:4RKS"
FT STRAND 174..180
FT /evidence="ECO:0007829|PDB:4RKS"
FT HELIX 188..195
FT /evidence="ECO:0007829|PDB:4RKS"
FT HELIX 201..219
FT /evidence="ECO:0007829|PDB:4RKS"
FT TURN 220..222
FT /evidence="ECO:0007829|PDB:4RKS"
FT HELIX 224..243
FT /evidence="ECO:0007829|PDB:4RKS"
FT TURN 244..246
FT /evidence="ECO:0007829|PDB:4RKS"
FT HELIX 252..264
FT /evidence="ECO:0007829|PDB:4RKS"
FT TURN 265..267
FT /evidence="ECO:0007829|PDB:4RKS"
FT STRAND 270..273
FT /evidence="ECO:0007829|PDB:4RKS"
FT STRAND 276..285
FT /evidence="ECO:0007829|PDB:4RKS"
FT HELIX 286..288
FT /evidence="ECO:0007829|PDB:4RKS"
FT HELIX 289..293
FT /evidence="ECO:0007829|PDB:4RKS"
FT STRAND 302..308
FT /evidence="ECO:0007829|PDB:4RKS"
SQ SEQUENCE 318 AA; 35201 MW; AD96174FA31C73AE CRC64;
MTYRSIGSTA YPTIGVVLLG GIANPVTRTP LHTSAGIAYS DSCGSIRSET RIYADEATHI
YFNGTESTDD NRSVRRVLDR YSSVFEEAFG TKTVSYSSQN FGILSGSSDA GAASIGAAIL
GLKPDLDPHD VENDLRAVSE SAGRSLFGGL TITWSDGFHA YTEKILDPEA FSGYSIVAFA
FDYQRNPSDV IHQNIVRSDL YPARKKHADE HAHMIKEYAK TNDIKGIFDL AQEDTEEYHS
ILRGVGVNVI RENMQKLISY LKLIRKDYWN AYIVTGGSNV YVAVESENAD RLFSIENTFG
SKKKMLRIVG GAWHRRPE
