Q3S2U3 · MOKG_MONPI
- Protein3-hydroxy-3-methylglutaryl coenzyme A reductase mokG
- GenemokG
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1052 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score4/5
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).
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).
Catalytic activity
- (R)-mevalonate + 2 NADP+ + CoA = (3S)-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
Biotechnology
Monacoline K acts as an inhibitor of HMG-CoA reductase involved in cholesterogenesis (PubMed:21821946).
Its hypocholesterolemic activity might be useful for lowering cholesterol levels in the blood and reduce artherosclerosis and coronary heart disease (PubMed:21821946).
Its hypocholesterolemic activity might be useful for lowering cholesterol levels in the blood and reduce artherosclerosis and coronary heart disease (PubMed:21821946).
Pathway
Polyketide biosynthesis; lovastatin biosynthesis.
Features
Showing features for active site.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Active site | 734 | Charge relay system | |||
Active site | 867 | Charge relay system | |||
Active site | 943 | Charge relay system | |||
Active site | 1039 | Proton donor | |||
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | peroxisomal membrane | |
Molecular Function | hydroxymethylglutaryl-CoA reductase (NADPH) activity | |
Biological Process | coenzyme A metabolic process | |
Biological Process | ergosterol biosynthetic process | |
Biological Process | isoprenoid biosynthetic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended name3-hydroxy-3-methylglutaryl coenzyme A reductase mokG
- EC number
- Short namesHMG-CoA reductase
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Monascus
Accessions
- Primary accessionQ3S2U3
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Transmembrane | 223-243 | Helical | |||
Transmembrane | 253-273 | Helical | |||
Transmembrane | 279-299 | Helical | |||
Transmembrane | 349-369 | Helical | |||
Transmembrane | 378-398 | Helical | |||
Transmembrane | 440-460 | Helical | |||
Keywords
- Cellular component
Phenotypes & Variants
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000436289 | 1-1052 | 3-hydroxy-3-methylglutaryl coenzyme A reductase mokG | ||
Glycosylation | 798 | N-linked (GlcNAc...) asparagine | |||
Glycosylation | 1043 | N-linked (GlcNAc...) asparagine | |||
Keywords
- PTM
PTM databases
Expression
Induction
Expression is controlled by the monacolin K cluster transcription regulator mokH (PubMed:19968298).
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Domain | 224-403 | SSD | |||
Region | 461-617 | Linker | |||
Region | 571-594 | Disordered | |||
Compositional bias | 574-591 | Pro residues | |||
Region | 618-1044 | Catalytic | |||
Sequence similarities
Belongs to the HMG-CoA reductase family.
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,052
- Mass (Da)112,803
- Last updated2005-10-11 v1
- Checksum6BC49D73EC37A298
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Compositional bias | 574-591 | Pro residues | |||
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
DQ176595 EMBL· GenBank· DDBJ | ABA02245.1 EMBL· GenBank· DDBJ | Genomic DNA |