| IED ID | IndEnz0010000667 |
| Enzyme Type ID | esterase000667 |
| Protein Name |
3-hydroxy-3-methylglutaryl coenzyme A reductase mlcD HMG-CoA reductase EC 1.1.1.34 Compactin biosynthesis protein G |
| Gene Name | mlcD |
| Organism | Penicillium citrinum |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Pezizomycotina leotiomyceta Eurotiomycetes Eurotiomycetidae Eurotiales (green and blue molds) Aspergillaceae Penicillium Penicillium citrinum |
| Enzyme Sequence | MVASLLPSRFRGRESMNQQHPLRSGNRALTSTLQFLSKTACLHPIHTVCTIAILASTTYVGLLKDSFFHGPANVDKAEWGSLVEGSRSLITGPQNGWKWQSFDGDADVLGDFNHQALMTLVFPGSYGVASQAASPFLAPLPVNLSVIDLPSTSSPLTAYSKDKVFAFSVEYSSAPELVAAVQEIPNNSADLKLQETQLIEMERQMWIMKAARAHTKRSLAQWVHDTWTESLDLIKSAQTLDVVVMVLGYISMHLTFVSLFLSMKKLGSKVWLATSVLLSSTFAFLLGLDVAIRLGVPMSMRLLSEGLPFLVVIVGFEKSITLTRAVLSYAVQHRKPQKIQSDQGSVTAIAESTINYAVRSAIREKGYNIVCHYVVEILLLVIGAVLGIQGGLQHFCVLAALILFFDCLLLFTFYTAILSIKLEVNRLKRHINMRYALEDEGLSQRTAESVATSNDAQDSARTYLFGNDMKGSSVPKFKFWMVVGFLIVNLVNIGSTLFQASSSGSLSSISSWTESLSGSAIKPPLEPFKVAGSGLDELLFQARGRGQSTMVTVLAPIKYELEYPSIHRGTSQLHEYGVGGKMVGSLLTSLEDPVLSKWVFVALALSVALNSYLFKAARLGIKDPNLPSHPVDPVELDQAESFNAAQNQTPQIQSSLQAPQTRVFTPTTTDSDSDASLVLIKASLKVTKRAEGKTATSELPVSRTQIELDNLLKQNTISELNDEDVVALSLRGKVPGYALEKSLKDCTRAVKVRRSIISRTPATAELTSMLEHSKLPYENYAWERVLGACCENVIGYMPVPVGVAGPIVIDGKSYFIPMATTEGVLVASASRGSKAINLGGGAVTVLTGDGMTRGPCVKFDVLERAGAAKIWLDSDVGQTVMKEAFNSTSRFARLQSMRTTIAGTHLYIRFKTTTGDAMGMNMISKGVEHALNVMATEAGFSDMNIITLSGNYCTDKKPSALNWIDGRGKGIVAEAIIPANVVRDVLKSDVDSMVQLNISKNLIGSAMAGSVGGFNAQAANLAAAIFIATGQDPAQVVESANCITLMNNLRGSLQISVSMPSIEVGTLGGGTILEPQGAMLDMLGVRGSHPTTPGENARQLARIIGSAVLAGELSLCAALAAGHLVKAHMAHNRSAPASSAPSRSVSPSGGTRTVPVPNNALRPSAAATDRARR |
| Enzyme Length | 1173 |
| Uniprot Accession Number | Q8J0F4 |
| Absorption | |
| Active Site | ACT_SITE 822; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P04035; ACT_SITE 956; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P04035; ACT_SITE 1032; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P04035; ACT_SITE 1128; /note=Proton donor; /evidence=ECO:0000255|PROSITE-ProRule:PRU10003 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=(R)-mevalonate + CoA + 2 NADP(+) = (3S)-hydroxy-3-methylglutaryl-CoA + 2 H(+) + 2 NADPH; Xref=Rhea:RHEA:15989, ChEBI:CHEBI:15378, ChEBI:CHEBI:36464, ChEBI:CHEBI:43074, ChEBI:CHEBI:57287, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.34; |
| DNA Binding | |
| EC Number | 1.1.1.34 |
| Enzyme Function | FUNCTION: HMG-CoA reductase; part of the gene cluster that mediates the biosynthesis of compactin, also known as mevastatin or ML-236B, and which acts as a potent competitive inhibitor of HMG-CoA reductase (PubMed:12172803, PubMed:12242508). Compactin biosynthesis is performed in two stages (PubMed:12172803). The first stage is catalyzed by the nonaketide synthase mlcA, which belongs to type I polyketide synthases and catalyzes the iterative nine-step formation of the polyketide (PubMed:12172803). This PKS stage is completed by the action of dehydrogenase mlcG, which catalyzes the NADPH-dependent reduction of the unsaturated tetra-, penta- and heptaketide intermediates that arise during the mlcA-mediated biosynthesis of the nonaketide chain and leads to dihydro-ML-236C carboxylate (PubMed:12172803). Covalently bound dihydro-ML-236C carboxylate is released from mlcA by the mlcF esterase (PubMed:12172803). Conversion of dihydro-ML-236C carboxylate into ML-236A carboxylate is subsequently performed with the participation of molecular oxygen and P450 monoogygenase mlcC (PubMed:12172803). Finally, mlcH performs the conversion of ML-236A carboxylate to ML-236B/compactin carboxylate through the addition of the side-chain diketide moiety produced by the diketide synthase mlcB (PubMed:12172803). HMG-CoA reductase mlcD may act as a down-regulator of compactin production and is involved in conferring resistance to ML-236B/compactin (PubMed:12242508). {ECO:0000269|PubMed:12172803, ECO:0000269|PubMed:12242508}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Polyketide biosynthesis. {ECO:0000305}. |
| nucleotide Binding | |
| Features | Active site (4); Chain (1); Compositional bias (1); Domain (1); Glycosylation (5); Region (4); Transmembrane (7) |
| Keywords | Endoplasmic reticulum;Glycoprotein;Membrane;NADP;Oxidoreductase;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | INDUCTION: Expression is induced at the beginning of the stationary phase, which is consistent with the timing of compactin production (PubMed:12172803). Expression is controlled by the ML-236B/compactin cluster transcription regulator mlcR (PubMed:12436257). {ECO:0000269|PubMed:12172803, ECO:0000269|PubMed:12436257}. |
| Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P04035}; Multi-pass membrane protein {ECO:0000255}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 125,847 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:15989 |
| Cross Reference Brenda |