MVK_METJA
ID MVK_METJA Reviewed; 312 AA.
AC Q58487;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Mevalonate kinase {ECO:0000255|HAMAP-Rule:MF_00217};
DE Short=MK {ECO:0000255|HAMAP-Rule:MF_00217};
DE Short=MVK {ECO:0000255|HAMAP-Rule:MF_00217};
DE EC=2.7.1.36 {ECO:0000255|HAMAP-Rule:MF_00217};
GN Name=mvk {ECO:0000255|HAMAP-Rule:MF_00217}; OrderedLocusNames=MJ1087;
OS Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM
OS 10045 / NBRC 100440) (Methanococcus jannaschii).
OC Archaea; Euryarchaeota; Methanomada group; Methanococci; Methanococcales;
OC Methanocaldococcaceae; Methanocaldococcus.
OX NCBI_TaxID=243232;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX PubMed=8688087; DOI=10.1126/science.273.5278.1058;
RA Bult C.J., White O., Olsen G.J., Zhou L., Fleischmann R.D., Sutton G.G.,
RA Blake J.A., FitzGerald L.M., Clayton R.A., Gocayne J.D., Kerlavage A.R.,
RA Dougherty B.A., Tomb J.-F., Adams M.D., Reich C.I., Overbeek R.,
RA Kirkness E.F., Weinstock K.G., Merrick J.M., Glodek A., Scott J.L.,
RA Geoghagen N.S.M., Weidman J.F., Fuhrmann J.L., Nguyen D., Utterback T.R.,
RA Kelley J.M., Peterson J.D., Sadow P.W., Hanna M.C., Cotton M.D.,
RA Roberts K.M., Hurst M.A., Kaine B.P., Borodovsky M., Klenk H.-P.,
RA Fraser C.M., Smith H.O., Woese C.R., Venter J.C.;
RT "Complete genome sequence of the methanogenic archaeon, Methanococcus
RT jannaschii.";
RL Science 273:1058-1073(1996).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES,
RP ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=10497066; DOI=10.1006/prep.1999.1106;
RA Huang K.-X., Scott A.I., Bennett G.N.;
RT "Overexpression, purification, and characterization of the thermostable
RT mevalonate kinase from Methanococcus jannaschii.";
RL Protein Expr. Purif. 17:33-40(1999).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, KINETIC PARAMETERS, AND MUTAGENESIS OF
RP ARG-196 AND LYS-272.
RX PubMed=12880770; DOI=10.1016/s1046-5928(03)00101-3;
RA Chu X., Liu X., Yau M., Leung Y.C., Li D.;
RT "Expression and purification of Arg196 and Lys272 mutants of mevalonate
RT kinase from Methanococcus jannaschii.";
RL Protein Expr. Purif. 30:210-218(2003).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS), ACTIVE SITE, AND REACTION
RP MECHANISM.
RX PubMed=11751891; DOI=10.1074/jbc.m110787200;
RA Yang D., Shipman L.W., Roessner C.A., Scott A.I., Sacchettini J.C.;
RT "Structure of the Methanococcus jannaschii mevalonate kinase, a member of
RT the GHMP kinase superfamily.";
RL J. Biol. Chem. 277:9462-9467(2002).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.69 ANGSTROMS).
RX PubMed=16021622; DOI=10.1002/prot.20541;
RA Badger J., Sauder J.M., Adams J.M., Antonysamy S., Bain K., Bergseid M.G.,
RA Buchanan S.G., Buchanan M.D., Batiyenko Y., Christopher J.A., Emtage S.,
RA Eroshkina A., Feil I., Furlong E.B., Gajiwala K.S., Gao X., He D.,
RA Hendle J., Huber A., Hoda K., Kearins P., Kissinger C., Laubert B.,
RA Lewis H.A., Lin J., Loomis K., Lorimer D., Louie G., Maletic M.,
RA Marsh C.D., Miller I., Molinari J., Muller-Dieckmann H.J., Newman J.M.,
RA Noland B.W., Pagarigan B., Park F., Peat T.S., Post K.W., Radojicic S.,
RA Ramos A., Romero R., Rutter M.E., Sanderson W.E., Schwinn K.D., Tresser J.,
RA Winhoven J., Wright T.A., Wu L., Xu J., Harris T.J.R.;
RT "Structural analysis of a set of proteins resulting from a bacterial
RT genomics project.";
RL Proteins 60:787-796(2005).
CC -!- FUNCTION: Catalyzes the phosphorylation of (R)-mevalonate (MVA) to (R)-
CC mevalonate 5-phosphate (MVAP). Functions in the mevalonate (MVA)
CC pathway leading to isopentenyl diphosphate (IPP), a key precursor for
CC the biosynthesis of isoprenoid compounds such as archaeal membrane
CC lipids. {ECO:0000255|HAMAP-Rule:MF_00217, ECO:0000269|PubMed:10497066,
CC ECO:0000269|PubMed:12880770}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-mevalonate + ATP = (R)-5-phosphomevalonate + ADP + H(+);
CC Xref=Rhea:RHEA:17065, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:36464, ChEBI:CHEBI:58146, ChEBI:CHEBI:456216;
CC EC=2.7.1.36; Evidence={ECO:0000255|HAMAP-Rule:MF_00217,
CC ECO:0000269|PubMed:10497066, ECO:0000269|PubMed:12880770};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00217,
CC ECO:0000269|PubMed:10497066};
CC -!- ACTIVITY REGULATION: Farnesyl- and geranyl-pyrophosphates are
CC competitive inhibitors. Slightly inhibited by high concentration of
CC ATP. {ECO:0000269|PubMed:10497066}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=68.5 uM for (RS)-mevalonate (at 70 degrees Celsius)
CC {ECO:0000269|PubMed:10497066, ECO:0000269|PubMed:12880770};
CC KM=106 uM for (RS)-mevalonate (at 34 degrees Celsius)
CC {ECO:0000269|PubMed:10497066, ECO:0000269|PubMed:12880770};
CC KM=92 uM for ATP (at 70 degrees Celsius)
CC {ECO:0000269|PubMed:10497066, ECO:0000269|PubMed:12880770};
CC KM=1180 uM for ATP (at 34 degrees Celsius)
CC {ECO:0000269|PubMed:10497066, ECO:0000269|PubMed:12880770};
CC Vmax=387 umol/min/mg enzyme (at 70 degrees Celsius)
CC {ECO:0000269|PubMed:10497066, ECO:0000269|PubMed:12880770};
CC Vmax=50.3 umol/min/mg enzyme (at 34 degrees Celsius)
CC {ECO:0000269|PubMed:10497066, ECO:0000269|PubMed:12880770};
CC pH dependence:
CC Optimum pH is 8.0-8.5. Exhibits at least 60% of its optimal activity
CC over a rather broad pH range, from 5 to 7.
CC {ECO:0000269|PubMed:10497066};
CC Temperature dependence:
CC Optimum temperature is 70-75 degrees Celsius. Highly thermostable.
CC Retains 100% of its activity after 24 hours of incubation at 70
CC degrees Celsius. At 90 and 100 degrees Celsius, the enzyme shows a
CC half-life of 15 and 5 min, respectively.
CC {ECO:0000269|PubMed:10497066};
CC -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate:
CC step 1/3. {ECO:0000255|HAMAP-Rule:MF_00217}.
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_00217,
CC ECO:0000269|PubMed:10497066}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the GHMP kinase family. Mevalonate kinase
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_00217}.
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DR EMBL; L77117; AAB99088.1; -; Genomic_DNA.
DR PIR; F64435; F64435.
DR RefSeq; WP_010870599.1; NC_000909.1.
DR PDB; 1KKH; X-ray; 2.40 A; A=1-312.
DR PDB; 1VIS; X-ray; 2.69 A; A=2-312.
DR PDBsum; 1KKH; -.
DR PDBsum; 1VIS; -.
DR AlphaFoldDB; Q58487; -.
DR SMR; Q58487; -.
DR STRING; 243232.MJ_1087; -.
DR EnsemblBacteria; AAB99088; AAB99088; MJ_1087.
DR GeneID; 1451983; -.
DR KEGG; mja:MJ_1087; -.
DR eggNOG; arCOG01028; Archaea.
DR HOGENOM; CLU_017814_0_0_2; -.
DR InParanoid; Q58487; -.
DR OMA; NTVCTYG; -.
DR OrthoDB; 90882at2157; -.
DR PhylomeDB; Q58487; -.
DR BioCyc; MetaCyc:MON-14622; -.
DR BRENDA; 2.7.1.36; 3260.
DR SABIO-RK; Q58487; -.
DR UniPathway; UPA00057; UER00098.
DR EvolutionaryTrace; Q58487; -.
DR Proteomes; UP000000805; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004496; F:mevalonate kinase activity; IBA:GO_Central.
DR GO; GO:0019287; P:isopentenyl diphosphate biosynthetic process, mevalonate pathway; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR Gene3D; 3.30.230.10; -; 1.
DR Gene3D; 3.30.70.890; -; 1.
DR HAMAP; MF_00217; Mevalonate_kinase; 1.
DR InterPro; IPR013750; GHMP_kinase_C_dom.
DR InterPro; IPR036554; GHMP_kinase_C_sf.
DR InterPro; IPR006204; GHMP_kinase_N_dom.
DR InterPro; IPR006203; GHMP_knse_ATP-bd_CS.
DR InterPro; IPR006205; Mev_gal_kin.
DR InterPro; IPR006206; Mevalonate/galactokinase.
DR InterPro; IPR022937; Mevalonate_kinase_arc.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR InterPro; IPR014721; Ribosomal_S5_D2-typ_fold_subgr.
DR PANTHER; PTHR43290; PTHR43290; 1.
DR Pfam; PF08544; GHMP_kinases_C; 1.
DR Pfam; PF00288; GHMP_kinases_N; 1.
DR PIRSF; PIRSF000530; Galactokinase; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55060; SSF55060; 1.
DR TIGRFAMs; TIGR00549; mevalon_kin; 1.
DR PROSITE; PS00627; GHMP_KINASES_ATP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cytoplasm; Isoprene biosynthesis; Kinase;
KW Lipid biosynthesis; Lipid metabolism; Magnesium; Nucleotide-binding;
KW Reference proteome; Transferase.
FT CHAIN 1..312
FT /note="Mevalonate kinase"
FT /id="PRO_0000156665"
FT ACT_SITE 155
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:11751891"
FT BINDING 104..114
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00217"
FT MUTAGEN 196
FT /note="R->K: 13.5-fold decrease in affinity for mevalonate,
FT whereas only little effect on affinity for ATP and on
FT reaction rate."
FT /evidence="ECO:0000269|PubMed:12880770"
FT MUTAGEN 196
FT /note="R->Q: 1900-fold decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:12880770"
FT MUTAGEN 196
FT /note="R->V: 63-fold decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:12880770"
FT MUTAGEN 272
FT /note="K->R,A: 13- to 26-fold decrease in catalytic
FT efficiency. Still thermostable."
FT /evidence="ECO:0000269|PubMed:12880770"
FT STRAND 1..12
FT /evidence="ECO:0007829|PDB:1KKH"
FT HELIX 16..19
FT /evidence="ECO:0007829|PDB:1KKH"
FT STRAND 23..38
FT /evidence="ECO:0007829|PDB:1KKH"
FT STRAND 41..48
FT /evidence="ECO:0007829|PDB:1KKH"
FT TURN 49..51
FT /evidence="ECO:0007829|PDB:1KKH"
FT STRAND 54..58
FT /evidence="ECO:0007829|PDB:1KKH"
FT TURN 59..61
FT /evidence="ECO:0007829|PDB:1KKH"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:1KKH"
FT HELIX 67..69
FT /evidence="ECO:0007829|PDB:1KKH"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:1KKH"
FT HELIX 74..86
FT /evidence="ECO:0007829|PDB:1KKH"
FT STRAND 95..101
FT /evidence="ECO:0007829|PDB:1KKH"
FT STRAND 105..109
FT /evidence="ECO:0007829|PDB:1KKH"
FT HELIX 111..125
FT /evidence="ECO:0007829|PDB:1KKH"
FT TURN 126..128
FT /evidence="ECO:0007829|PDB:1KKH"
FT HELIX 133..147
FT /evidence="ECO:0007829|PDB:1KKH"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:1KKH"
FT HELIX 154..161
FT /evidence="ECO:0007829|PDB:1KKH"
FT STRAND 163..170
FT /evidence="ECO:0007829|PDB:1KKH"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:1KKH"
FT HELIX 177..184
FT /evidence="ECO:0007829|PDB:1KKH"
FT STRAND 188..194
FT /evidence="ECO:0007829|PDB:1KKH"
FT HELIX 200..208
FT /evidence="ECO:0007829|PDB:1KKH"
FT HELIX 213..229
FT /evidence="ECO:0007829|PDB:1KKH"
FT HELIX 233..248
FT /evidence="ECO:0007829|PDB:1KKH"
FT TURN 249..251
FT /evidence="ECO:0007829|PDB:1KKH"
FT HELIX 255..267
FT /evidence="ECO:0007829|PDB:1KKH"
FT STRAND 268..273
FT /evidence="ECO:0007829|PDB:1KKH"
FT STRAND 275..285
FT /evidence="ECO:0007829|PDB:1KKH"
FT HELIX 288..290
FT /evidence="ECO:0007829|PDB:1KKH"
FT HELIX 291..299
FT /evidence="ECO:0007829|PDB:1KKH"
FT STRAND 304..308
FT /evidence="ECO:0007829|PDB:1KKH"
SQ SEQUENCE 312 AA; 35177 MW; DFF9E5B869728298 CRC64;
MIIETPSKVI LFGEHAVVYG YRAISMAIDL TSTIEIKETQ EDEIILNLND LNKSLGLNLN
EIKNINPNNF GDFKYCLCAI KNTLDYLNIE PKTGFKINIS SKIPISCGLG SSASITIGTI
KAVSGFYNKE LKDDEIAKLG YMVEKEIQGK ASITDTSTIT YKGILEIKNN KFRKIKGEFE
EFLKNCKFLI VYAEKRKKKT AELVNEVAKI ENKDEIFKEI DKVIDEALKI KNKEDFGKLM
TKNHELLKKL NISTPKLDRI VDIGNRFGFG AKLTGAGGGG CVIILVNEEK EKELLKELNK
EDVRIFNCRM MN
