MVAA_PSEMV
ID MVAA_PSEMV Reviewed; 428 AA.
AC P13702;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase;
DE Short=HMG-CoA reductase;
DE EC=1.1.1.88;
GN Name=mvaA;
OS Pseudomonas mevalonii.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales.
OX NCBI_TaxID=32044;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=2656635; DOI=10.1128/jb.171.6.2994-3001.1989;
RA Beach M.J., Rodwell V.W.;
RT "Cloning, sequencing, and overexpression of mvaA, which encodes Pseudomonas
RT mevalonii 3-hydroxy-3-methylglutaryl coenzyme A reductase.";
RL J. Bacteriol. 171:2994-3001(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-4.
RX PubMed=2477360; DOI=10.1128/jb.171.10.5567-5571.1989;
RA Wang Y., Beach M.J., Rodwell V.W.;
RT "(S)-3-hydroxy-3-methylglutaryl coenzyme A reductase, a product of the mva
RT operon of Pseudomonas mevalonii, is regulated at the transcriptional
RT level.";
RL J. Bacteriol. 171:5567-5571(1989).
RN [3]
RP MUTAGENESIS.
RX PubMed=2123872; DOI=10.1016/s0021-9258(18)45788-2;
RA Wang Y., Darnay B.G., Rodwell V.W.;
RT "Identification of the principal catalytically important acidic residue of
RT 3-hydroxy-3-methylglutaryl coenzyme A reductase.";
RL J. Biol. Chem. 265:21634-21641(1990).
RN [4]
RP ACTIVE SITE HIS-381.
RX PubMed=1634543; DOI=10.1016/s0021-9258(18)42146-1;
RA Darnay B.G., Wang Y., Rodwell V.W.;
RT "Identification of the catalytically important histidine of 3-hydroxy-3-
RT methylglutaryl-coenzyme A reductase.";
RL J. Biol. Chem. 267:15064-15070(1992).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=10377386; DOI=10.1073/pnas.96.13.7167;
RA Tabernero L., Bochar D.A., Rodwell V.W., Stauffacher C.V.;
RT "Substrate-induced closure of the flap domain in the ternary complex
RT structures provides insights into the mechanism of catalysis by 3-hydroxy-
RT 3-methylglutaryl-CoA reductase.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:7167-7171(1999).
CC -!- FUNCTION: P.mevalonii can use mevalonate as sole carbon source. With
CC this enzyme mevalonate is deacetylated to HMG-CoA.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-mevalonate + CoA + 2 NAD(+) = (3S)-hydroxy-3-
CC methylglutaryl-CoA + 2 H(+) + 2 NADH; Xref=Rhea:RHEA:14833,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:36464, ChEBI:CHEBI:43074,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.88;
CC -!- PATHWAY: Metabolic intermediate metabolism; (R)-mevalonate degradation;
CC (S)-3-hydroxy-3-methylglutaryl-CoA from (R)-mevalonate: step 1/1.
CC -!- SUBUNIT: Homotetramer.
CC -!- INDUCTION: Coinduction with mevalonate transport system.
CC -!- SIMILARITY: Belongs to the HMG-CoA reductase 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; M24015; AAA25837.1; -; Genomic_DNA.
DR EMBL; M29727; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PDB; 1QAX; X-ray; 2.80 A; A/B=1-428.
DR PDB; 1QAY; X-ray; 2.80 A; A/B=1-428.
DR PDB; 1R31; X-ray; 2.10 A; A/B=1-428.
DR PDB; 1R7I; X-ray; 2.21 A; A/B=1-428.
DR PDB; 1T02; X-ray; 2.60 A; A/B=1-428.
DR PDB; 4I4B; X-ray; 1.70 A; A/B=1-428.
DR PDB; 4I56; X-ray; 1.50 A; A/B=1-428.
DR PDB; 4I64; X-ray; 1.75 A; A/B=1-428.
DR PDB; 4I6A; X-ray; 1.85 A; A/B=1-428.
DR PDB; 4I6W; X-ray; 1.66 A; A/B=1-428.
DR PDB; 4I6Y; X-ray; 1.45 A; A/B=1-428.
DR PDBsum; 1QAX; -.
DR PDBsum; 1QAY; -.
DR PDBsum; 1R31; -.
DR PDBsum; 1R7I; -.
DR PDBsum; 1T02; -.
DR PDBsum; 4I4B; -.
DR PDBsum; 4I56; -.
DR PDBsum; 4I64; -.
DR PDBsum; 4I6A; -.
DR PDBsum; 4I6W; -.
DR PDBsum; 4I6Y; -.
DR AlphaFoldDB; P13702; -.
DR SMR; P13702; -.
DR DrugBank; DB03169; (S)-Hmg-Coa.
DR DrugBank; DB01992; Coenzyme A.
DR DrugBank; DB03518; Mevalonic acid.
DR DrugBank; DB03785; Mevinolinic acid.
DR KEGG; ag:AAA25837; -.
DR BioCyc; MetaCyc:MON-11829; -.
DR BRENDA; 1.1.1.88; 5143.
DR SABIO-RK; P13702; -.
DR UniPathway; UPA00257; UER00367.
DR EvolutionaryTrace; P13702; -.
DR GO; GO:0140643; F:hydroxymethylglutaryl-CoA reductase (NADH) activity; IEA:UniProtKB-EC.
DR GO; GO:0004420; F:hydroxymethylglutaryl-CoA reductase (NADPH) activity; IEA:InterPro.
DR GO; GO:0015936; P:coenzyme A metabolic process; IEA:InterPro.
DR CDD; cd00644; HMG-CoA_reductase_classII; 1.
DR Gene3D; 3.90.770.10; -; 2.
DR InterPro; IPR002202; HMG_CoA_Rdtase.
DR InterPro; IPR004553; HMG_CoA_Rdtase_bac-typ.
DR InterPro; IPR023074; HMG_CoA_Rdtase_cat_sf.
DR InterPro; IPR023076; HMG_CoA_Rdtase_CS.
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 SUPFAM; SSF55035; SSF55035; 1.
DR SUPFAM; SSF56542; SSF56542; 1.
DR TIGRFAMs; TIGR00532; HMG_CoA_R_NAD; 1.
DR PROSITE; PS00066; HMG_COA_REDUCTASE_1; 1.
DR PROSITE; PS00318; HMG_COA_REDUCTASE_2; 1.
DR PROSITE; PS01192; HMG_COA_REDUCTASE_3; 1.
DR PROSITE; PS50065; HMG_COA_REDUCTASE_4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; NAD; Oxidoreductase.
FT CHAIN 1..428
FT /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT /id="PRO_0000114467"
FT ACT_SITE 83
FT /note="Charge relay system"
FT ACT_SITE 267
FT /note="Charge relay system"
FT ACT_SITE 283
FT /note="Charge relay system"
FT ACT_SITE 381
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10003,
FT ECO:0000269|PubMed:1634543"
FT MUTAGEN 52
FT /note="E->Q: No loss of activity."
FT /evidence="ECO:0000269|PubMed:2123872"
FT MUTAGEN 83
FT /note="E->Q: Greatly reduced activity."
FT /evidence="ECO:0000269|PubMed:2123872"
FT MUTAGEN 183
FT /note="D->A,N: Reduced activity."
FT /evidence="ECO:0000269|PubMed:2123872"
FT MUTAGEN 381
FT /note="H->A,N,Q,K: Reduced activity."
FT /evidence="ECO:0000269|PubMed:2123872"
FT HELIX 10..12
FT /evidence="ECO:0007829|PDB:4I6Y"
FT HELIX 15..26
FT /evidence="ECO:0007829|PDB:4I6Y"
FT HELIX 30..37
FT /evidence="ECO:0007829|PDB:4I6Y"
FT HELIX 44..50
FT /evidence="ECO:0007829|PDB:4I6Y"
FT STRAND 51..65
FT /evidence="ECO:0007829|PDB:4I6Y"
FT STRAND 77..80
FT /evidence="ECO:0007829|PDB:4I6Y"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:1QAX"
FT HELIX 86..98
FT /evidence="ECO:0007829|PDB:4I6Y"
FT TURN 99..101
FT /evidence="ECO:0007829|PDB:4I6Y"
FT STRAND 103..107
FT /evidence="ECO:0007829|PDB:4I6Y"
FT STRAND 111..120
FT /evidence="ECO:0007829|PDB:4I6Y"
FT HELIX 124..133
FT /evidence="ECO:0007829|PDB:4I6Y"
FT HELIX 135..144
FT /evidence="ECO:0007829|PDB:4I6Y"
FT HELIX 147..151
FT /evidence="ECO:0007829|PDB:4I6Y"
FT STRAND 155..164
FT /evidence="ECO:0007829|PDB:4I6Y"
FT STRAND 172..180
FT /evidence="ECO:0007829|PDB:4I6Y"
FT HELIX 187..205
FT /evidence="ECO:0007829|PDB:4I6Y"
FT STRAND 208..214
FT /evidence="ECO:0007829|PDB:4I6Y"
FT STRAND 221..229
FT /evidence="ECO:0007829|PDB:4I6Y"
FT HELIX 231..234
FT /evidence="ECO:0007829|PDB:4I6Y"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:4I6Y"
FT HELIX 241..257
FT /evidence="ECO:0007829|PDB:4I6Y"
FT HELIX 259..279
FT /evidence="ECO:0007829|PDB:4I6Y"
FT HELIX 284..295
FT /evidence="ECO:0007829|PDB:4I6Y"
FT TURN 296..298
FT /evidence="ECO:0007829|PDB:4I6Y"
FT STRAND 304..309
FT /evidence="ECO:0007829|PDB:4I6Y"
FT STRAND 315..322
FT /evidence="ECO:0007829|PDB:4I6Y"
FT STRAND 327..329
FT /evidence="ECO:0007829|PDB:4I6Y"
FT TURN 330..334
FT /evidence="ECO:0007829|PDB:4I6Y"
FT HELIX 336..345
FT /evidence="ECO:0007829|PDB:4I6Y"
FT HELIX 350..374
FT /evidence="ECO:0007829|PDB:4I6Y"
FT HELIX 378..393
FT /evidence="ECO:0007829|PDB:4I4B"
FT TURN 398..400
FT /evidence="ECO:0007829|PDB:1QAX"
FT HELIX 405..408
FT /evidence="ECO:0007829|PDB:4I4B"
FT TURN 409..411
FT /evidence="ECO:0007829|PDB:4I4B"
FT HELIX 415..420
FT /evidence="ECO:0007829|PDB:4I4B"
SQ SEQUENCE 428 AA; 45590 MW; 3302701FE6E1B1F3 CRC64;
MSLDSRLPAF RNLSPAARLD HIGQLLGLSH DDVSLLANAG ALPMDIANGM IENVIGTFEL
PYAVASNFQI NGRDVLVPLV VEEPSIVAAA SYMAKLARAN GGFTTSSSAP LMHAQVQIVG
IQDPLNARLS LLRRKDEIIE LANRKDQLLN SLGGGCRDIE VHTFADTPRG PMLVAHLIVD
VRDAMGANTV NTMAEAVAPL MEAITGGQVR LRILSNLADL RLARAQVRIT PQQLETAEFS
GEAVIEGILD AYAFAAVDPY RAATHNKGIM NGIDPLIVAT GNDWRAVEAG AHAYACRSGH
YGSLTTWEKD NNGHLVGTLE MPMPVGLVGG ATKTHPLAQL SLRILGVKTA QALAEIAVAV
GLAQNLGAMR ALATEGIQRG HMALHARNIA VVAGARGDEV DWVARQLVEY HDVRADRAVA
LLKQKRGQ
