| IED ID | IndEnz0010000670 |
| Enzyme Type ID | esterase000670 |
| Protein Name |
ML-236A carboxylate methylbutanoyltransferase mlcH EC 2.3.1.- Compactin biosynthesis protein H |
| Gene Name | mlcH |
| 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 | MAPSIDVIPTAASTAAGMISDMEAAFKSAVKLKQIPGAVVMARSMNGDIDYTRCFGARTVERDECQRLPPMEIDTPLRLASATKLLTTIMALQCMEQGLVDLDENVNRLLPDLSDMQVLTGFDAAGNAIMRDREGIIKLRHLLTHTSGLSYAFLHPLLQEYMAKGYLKTAEKFGIQSRLAPPAINDPGVEWIYGANLDWAGKLIERATGVDLEEFMQKNICEPLGITDMTFKLQQRPDMLARRSDQTRRNENGSLRYDDSVYFRHDGEECFGGQGVFCGPESYMKVLNSLMKHDGLLLKKDTIELMFQPALDAELEKKMNDHMDTTPHINYGAALPPVMRRNFGLGGIIAMGDLDGHNWRREGSLTFGGGPNIVWQIDPTVGLCTLVVFQLEPWNDPICKDLTRKFEKAMYSQVKCRN |
| Enzyme Length | 418 |
| Uniprot Accession Number | Q8J0G0 |
| Absorption | |
| Active Site | ACT_SITE 81; /note=Acyl-ester intermediate; /evidence=ECO:0000250|UniProtKB:Q9Y7D1 |
| Activity Regulation | |
| Binding Site | BINDING 78; /note=Monacolin J; /evidence=ECO:0000250|UniProtKB:Q9Y7D1; BINDING 178; /note=Monacolin J; /evidence=ECO:0000250|UniProtKB:Q9Y7D1; BINDING 193; /note=Monacolin J; /evidence=ECO:0000250|UniProtKB:Q9Y7D1; BINDING 262; /note=Monacolin J; /evidence=ECO:0000250|UniProtKB:Q9Y7D1; BINDING 370; /note=2-methylbutanoate; via amide nitrogen; /evidence=ECO:0000250|UniProtKB:Q9Y7D1 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=(S)-2-methylbutanoyl-[2-methylbutanoate polyketide synthase] + ML-236A carboxylate = holo-[2-methylbutanoate polyketide synthase] + mevinic carboxylate; Xref=Rhea:RHEA:57636, Rhea:RHEA-COMP:10260, Rhea:RHEA-COMP:10261, ChEBI:CHEBI:64479, ChEBI:CHEBI:82764, ChEBI:CHEBI:142048, ChEBI:CHEBI:142050; Evidence={ECO:0000305}; |
| DNA Binding | |
| EC Number | 2.3.1.- |
| Enzyme Function | FUNCTION: Compactin diketide synthase; 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). 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). {ECO:0000269|PubMed:12172803}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Polyketide biosynthesis. {ECO:0000303|PubMed:12172803}. |
| nucleotide Binding | |
| Features | Active site (1); Binding site (5); Chain (1) |
| Keywords | Acyltransferase;Hydrolase;Transferase |
| 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 | |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 46,688 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:57636 |
| Cross Reference Brenda |