HMDH_HALS3
ID HMDH_HALS3 Reviewed; 405 AA.
AC B0R6J9;
DT 14-MAY-2014, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 1.
DT 25-MAY-2022, entry version 80.
DE RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase;
DE Short=HMG-CoA reductase;
DE Short=HMGR;
DE EC=1.1.1.34;
GN Name=hmgA; OrderedLocusNames=OE_3637R;
OS Halobacterium salinarum (strain ATCC 29341 / DSM 671 / R1).
OC Archaea; Euryarchaeota; Stenosarchaea group; Halobacteria; Halobacteriales;
OC Halobacteriaceae; Halobacterium.
OX NCBI_TaxID=478009;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 29341 / DSM 671 / R1;
RX PubMed=18313895; DOI=10.1016/j.ygeno.2008.01.001;
RA Pfeiffer F., Schuster S.C., Broicher A., Falb M., Palm P., Rodewald K.,
RA Ruepp A., Soppa J., Tittor J., Oesterhelt D.;
RT "Evolution in the laboratory: the genome of Halobacterium salinarum strain
RT R1 compared to that of strain NRC-1.";
RL Genomics 91:335-346(2008).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, KINETIC PARAMETERS, ACTIVITY REGULATION,
RP SUBCELLULAR LOCATION, PATHWAY, AND SUBUNIT.
RC STRAIN=ATCC 29341 / DSM 671 / R1;
RX PubMed=3633268; DOI=10.1016/s0021-9258(17)35685-5;
RA Cabrera J.A., Bolds J., Shields P.E., Havel C.M., Watson J.A.;
RT "Isoprenoid synthesis in Halobacterium halobium. Modulation of 3-hydroxy-3-
RT methylglutaryl coenzyme a concentration in response to mevalonate
RT availability.";
RL J. Biol. Chem. 261:3578-3583(1986).
CC -!- FUNCTION: Catalyzes the NADPH-dependent reductive deacylation of (S)-3-
CC hydroxy-3-methylglutaryl-CoA (HMG-CoA) to (R)-mevalonate. Cannot use
CC NADH instead of NADPH. Functions in the mevalonate (MVA) pathway
CC leading to isopentenyl diphosphate (IPP), a key precursor for the
CC biosynthesis of isoprenoid compounds such as archaeal membrane lipids.
CC {ECO:0000269|PubMed:3633268}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-mevalonate + CoA + 2 NADP(+) = (3S)-hydroxy-3-
CC methylglutaryl-CoA + 2 H(+) + 2 NADPH; Xref=Rhea:RHEA:15989,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:36464, ChEBI:CHEBI:43074,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.34;
CC Evidence={ECO:0000269|PubMed:3633268};
CC -!- ACTIVITY REGULATION: Is competitively inhibited by lovastatin (formerly
CC called mevinolin). Lovastatin also blocks the growth of H.salinarum,
CC and this effect is reversed by addition of mevalonate, indicating the
CC critical role that the mevalonate pathway plays in isoprenoid
CC biosynthesis by these archaea. {ECO:0000269|PubMed:3633268}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=20 uM for (S)-HMG-CoA {ECO:0000269|PubMed:3633268};
CC Note=KCl concentrations greater than 2 M are required for maximum
CC reductase activity.;
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC {ECO:0000269|PubMed:3633268}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:3633268}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:3633268}.
CC -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
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DR EMBL; AM774415; CAP14368.1; -; Genomic_DNA.
DR RefSeq; WP_010903374.1; NC_010364.1.
DR AlphaFoldDB; B0R6J9; -.
DR SMR; B0R6J9; -.
DR EnsemblBacteria; CAP14368; CAP14368; OE_3637R.
DR GeneID; 5953140; -.
DR GeneID; 62887231; -.
DR KEGG; hsl:OE_3637R; -.
DR HOGENOM; CLU_001734_2_2_2; -.
DR OMA; DDKMTRA; -.
DR PhylomeDB; B0R6J9; -.
DR UniPathway; UPA00058; UER00103.
DR Proteomes; UP000001321; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004420; F:hydroxymethylglutaryl-CoA reductase (NADPH) activity; IEA:UniProtKB-EC.
DR GO; GO:0015936; P:coenzyme A metabolic process; IEA:InterPro.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:UniProtKB-KW.
DR CDD; cd00643; HMG-CoA_reductase_classI; 1.
DR Gene3D; 3.30.70.420; -; 1.
DR Gene3D; 3.90.770.10; -; 1.
DR InterPro; IPR002202; HMG_CoA_Rdtase.
DR InterPro; IPR023074; HMG_CoA_Rdtase_cat_sf.
DR InterPro; IPR023076; HMG_CoA_Rdtase_CS.
DR InterPro; IPR004554; HMG_CoA_Rdtase_eu_arc.
DR InterPro; IPR009023; HMG_CoA_Rdtase_NAD(P)-bd_sf.
DR InterPro; IPR009029; HMG_CoA_Rdtase_sub-bd_dom_sf.
DR PANTHER; PTHR10572; PTHR10572; 1.
DR Pfam; PF00368; HMG-CoA_red; 1.
DR PRINTS; PR00071; HMGCOARDTASE.
DR SUPFAM; SSF55035; SSF55035; 1.
DR SUPFAM; SSF56542; SSF56542; 1.
DR TIGRFAMs; TIGR00533; HMG_CoA_R_NADP; 1.
DR PROSITE; PS00066; HMG_COA_REDUCTASE_1; 1.
DR PROSITE; PS00318; HMG_COA_REDUCTASE_2; 1.
DR PROSITE; PS50065; HMG_COA_REDUCTASE_4; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Isoprene biosynthesis; Lipid biosynthesis; Lipid metabolism;
KW NADP; Oxidoreductase.
FT CHAIN 1..405
FT /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT /id="PRO_0000429252"
FT ACT_SITE 101
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 305
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 400
FT /note="Proton donor"
FT /evidence="ECO:0000250"
SQ SEQUENCE 405 AA; 41092 MW; E458FBBA16A054D8 CRC64;
MPDDASDLAD RVQAGDLRLY ELDDETDADT AAAARRAVLE RETDADTDAL GAFAFDADQA
ADTAVENLTG GAQLPLGVAG PVALSGGAAD GEYYLPMATT EGALVASVNR GCSAITAAGG
ANARVTKTGM TRAPVFRVAD VTEGAEVAQW ADDNTDALAA AAESTTSHGE LTDVTPYVVG
DNVYLRFRYD TKDAMGMNMA TIATEAASEL VEDETPAELV AVSGNLCTDK KPAAINAVEG
RGRTVTADVT IPQDVVEERF DTTPAAIEEA NTRKNLIGSA KAGSLGFNAH AANVVAAVFL
ATGQDAAQVV EGANAITTVE ARDDALYASV NLASLEVGTV GGGTTLPTQR EALDVLGVRG
GGDPAGANAD ALAEIIAVGA LAGEINLLAA LASRRLSAAH ADLGR
