| IED ID | IndEnz0010000702 |
| Enzyme Type ID | esterase000702 |
| Protein Name |
3-hydroxy-3-methylglutaryl coenzyme A reductase mokG HMG-CoA reductase EC 1.1.1.34 Monacolin K biosynthesis protein G |
| Gene Name | mokG |
| Organism | Monascus pilosus (Red mold) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Pezizomycotina leotiomyceta Eurotiomycetes Eurotiomycetidae Eurotiales (green and blue molds) Aspergillaceae Monascus Monascus pilosus (Red mold) |
| Enzyme Sequence | MASAAVTPKLGWVQHQVTNGLHAVVGQVCRHPIHTLLVTALIAATTYLHVLEGTFRAANLGPGSKTDAAPFDVQSFLWGSRSLRLGETSSWRWQVGDLSEATGDGQVNHHWALVTLSFPGASVDDRSPAFLWNALPDSVGAEPITPTSNFFTSISNEFSLAFRVPYTQLSDFLEAVEFVASDKEDRSWAIRFPHGEGKPISLGRWLGNSWLSFLHRAKHAETVDMAIIGLGYLALNMTLVSLFRAMRQLGSRFWLAASVLLSGAFAFVFGLGVTTACGVPVDMLLLSEGIPFLVLTVGFEKPIRFTRAVLYASNQLRRGLQQRDVADKHDSRQRHMIPNAMLFAINREGWSIVQSYLLEIGALALGAVFRPRERFGQFCFLAAWMVLFDAILLFTFYATILCVKLEVTRMQNPGTLDLADDQHGPRIFGYKVNPTSLARWKLIMVGGFVLFNVLQLSSFFYRIMGGFMTNAALTPTTVSPFKVAANGLNDIYLAARAGGVETWVTVLPPIRYVMEASGLEMSAGRRPVFDGVLAGLESPLGRLCLMGALVFSLYLNNHLIPAARWHFSPGAPKESAAPAPPSSPASVPSAVPVPAPSSRSFEEIEALFKANQAESLTDDELAELCLRGKIAGYSLEKTLESIASAGSSSTATTRLEAFTRAVRIRRAAVSRTPSTRDLSGGIQESLLPYRNYNYELVHGACCENVIGYLPLPLGLAGPMVIDGQAYFIPMATTEGVLVASASRGCKAINTGGGAVTMLKGDGMTRGPCLGFPSAKRAAEAQRWVESPVGHQVLTDAFNATSRFARLQTLTVAQAGTYLYIRFRTTTGDAMGMNMISKGVEKALQAMTAHGFPDMNTITLSGNFCADKKSAAINWIGGRGKSVIAEATIPADTVRKVLKTDIDALVELNTAKNLVGSAMAGSMGGFNAHASNLVQAVFLATGQDPAQNVESSSCITTMKKIDGNLHIAVSMPSMEVGTIGGGTILEAQGAMLDLLGVRGAHPTDPGANARRLARIVAAAVLAGELSTCSALAAGHLVNAHMRHNRSAASSEKK |
| Enzyme Length | 1052 |
| Uniprot Accession Number | Q3S2U3 |
| Absorption | |
| Active Site | ACT_SITE 734; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P04035; ACT_SITE 867; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P04035; ACT_SITE 943; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P04035; ACT_SITE 1039; /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 monakolin K, also known as lovastatin, and which acts as a potent competitive inhibitor of HMG-CoA reductase (PubMed:18578535). Monakolin K biosynthesis is performed in two stages (PubMed:19693441). The first stage is catalyzed by the nonaketide synthase mokA, which belongs to type I polyketide synthases and catalyzes the iterative nine-step formation of the polyketide (PubMed:18578535, PubMed:19693441). This PKS stage is completed by the action of dehydrogenase mokE, which catalyzes the NADPH-dependent reduction of the unsaturated tetra-, penta- and heptaketide intermediates that arise during the mokA-mediated biosynthesis of the nonaketide chain and leads to dihydromonacolin L (PubMed:19693441). Covalently bound dihydromonacolin L is released from mokA by the mokD esterase (By similarity). Conversion of dihydromonacolin L into monacolin L and then monacolin J is subsequently performed with the participation of molecular oxygen and P450 monoogygenase mokC (PubMed:19693441). Finally, mokF performs the conversion of monacoline J to monacoline K through the addition of the side-chain diketide moiety (2R)-2-methylbutanoate produced by the diketide synthase mokB (PubMed:19693441). HMG-CoA reductase mokG may act as a down-regulator of monacolin K production (PubMed:18578535). {ECO:0000250|UniProtKB:Q0C8M2, ECO:0000303|PubMed:18578535, ECO:0000303|PubMed:19693441}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Polyketide biosynthesis; lovastatin biosynthesis. {ECO:0000303|PubMed:18578535}. |
| nucleotide Binding | |
| Features | Active site (4); Chain (1); Compositional bias (1); Domain (1); Glycosylation (2); Region (3); Transmembrane (6) |
| Keywords | Endoplasmic reticulum;Glycoprotein;Membrane;NADP;Oxidoreductase;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | INDUCTION: Expression is controlled by the monacolin K cluster transcription regulator mokH (PubMed:19968298). {ECO:0000269|PubMed:19968298}. |
| 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 | 112,803 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:15989 |
| Cross Reference Brenda |