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 13-SEP-2023, entry version 136. 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; Pseudomonadota; Gammaproteobacteria; Pseudomonadales; OC Pseudomonadaceae; Pseudomonas. 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:MONOMER-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; 1.10.8.660; -; 1. 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 NCBIfam; TIGR00532; HMG_CoA_R_NAD; 1. DR PANTHER; PTHR10572; 3-HYDROXY-3-METHYLGLUTARYL-COENZYME A REDUCTASE; 1. DR PANTHER; PTHR10572:SF24; 3-HYDROXY-3-METHYLGLUTARYL-COENZYME A REDUCTASE; 1. DR Pfam; PF00368; HMG-CoA_red; 1. DR SUPFAM; SSF55035; NAD-binding domain of HMG-CoA reductase; 1. DR SUPFAM; SSF56542; Substrate-binding domain of HMG-CoA reductase; 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 //