ID   HMDH_METTH              Reviewed;         397 AA.
AC   O26662;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   25-MAY-2022, entry version 133.
DE   RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase;
DE            Short=HMG-CoA reductase;
DE            EC=1.1.1.34;
GN   Name=hmgA; OrderedLocusNames=MTH_562;
OS   Methanothermobacter thermautotrophicus (strain ATCC 29096 / DSM 1053 / JCM
OS   10044 / NBRC 100330 / Delta H) (Methanobacterium thermoautotrophicum).
OC   Archaea; Euryarchaeota; Methanomada group; Methanobacteria;
OC   Methanobacteriales; Methanobacteriaceae; Methanothermobacter.
OX   NCBI_TaxID=187420;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 29096 / DSM 1053 / JCM 10044 / NBRC 100330 / Delta H;
RX   PubMed=9371463; DOI=10.1128/jb.179.22.7135-7155.1997;
RA   Smith D.R., Doucette-Stamm L.A., Deloughery C., Lee H.-M., Dubois J.,
RA   Aldredge T., Bashirzadeh R., Blakely D., Cook R., Gilbert K., Harrison D.,
RA   Hoang L., Keagle P., Lumm W., Pothier B., Qiu D., Spadafora R., Vicare R.,
RA   Wang Y., Wierzbowski J., Gibson R., Jiwani N., Caruso A., Bush D.,
RA   Safer H., Patwell D., Prabhakar S., McDougall S., Shimer G., Goyal A.,
RA   Pietrovski S., Church G.M., Daniels C.J., Mao J.-I., Rice P., Noelling J.,
RA   Reeve J.N.;
RT   "Complete genome sequence of Methanobacterium thermoautotrophicum deltaH:
RT   functional analysis and comparative genomics.";
RL   J. Bacteriol. 179:7135-7155(1997).
CC   -!- FUNCTION: Converts HMG-CoA to mevalonate. {ECO:0000250}.
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   -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC       biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC   -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
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DR   EMBL; AE000666; AAB85068.1; -; Genomic_DNA.
DR   PIR; D69174; D69174.
DR   RefSeq; WP_010876201.1; NC_000916.1.
DR   AlphaFoldDB; O26662; -.
DR   SMR; O26662; -.
DR   STRING; 187420.MTH_562; -.
DR   EnsemblBacteria; AAB85068; AAB85068; MTH_562.
DR   GeneID; 1470523; -.
DR   KEGG; mth:MTH_562; -.
DR   PATRIC; fig|187420.15.peg.542; -.
DR   HOGENOM; CLU_001734_2_2_2; -.
DR   OMA; DDKMTRA; -.
DR   UniPathway; UPA00058; UER00103.
DR   Proteomes; UP000005223; Chromosome.
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; PS50065; HMG_COA_REDUCTASE_4; 1.
PE   3: Inferred from homology;
KW   Isoprene biosynthesis; NADP; Oxidoreductase; Reference proteome.
FT   CHAIN           1..397
FT                   /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT                   /id="PRO_0000114462"
FT   ACT_SITE        96
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        301
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        391
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   397 AA;  42160 MW;  C4AA45A82EF211E4 CRC64;
     MSIMDDLMEG RIKLYEIERH VPVDEAVRIR REFIERTCGV KLEHVSNYSI DMERASRRNI
     ENPIGVVQIP LGVAGPLRVR GEHADGEYYV PLATSEGALV ASVNRGCSVI TRAGGATVRV
     TGDSMTRAPV IRTGSVVEAL QLREWIYENM DALREEAEST TRHGKLVKID PIIVAGSYVY
     PRFVYTTGDS MGMNMVTIAT ERALELLTRE TGAHVIALSG NLCTDKKPAA VNLIEGRGKS
     ITAEITVPGE MVESVLKTTP EAVVEVNTAK NLIGSAAAGS MGFNAHYANI IGAIFLATGQ
     DEAHIVEGSL GVTIAEERKG DLYFAVNLPD VPLATVGGGT GLETASECLD IMGVRGGGRV
     HAFAEIVGGA VLAGELSLMG ALAAGHLARA HSELGRG