Q3S2U3 · MOKG_MONPI

  • Protein
    3-hydroxy-3-methylglutaryl coenzyme A reductase mokG
  • Gene
    mokG
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    4/5

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).

Catalytic activity

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).

Pathway

Polyketide biosynthesis; lovastatin biosynthesis.

Features

Showing features for active site.

TypeIDPosition(s)Description
Active site734Charge relay system
Active site867Charge relay system
Active site943Charge relay system
Active site1039Proton donor

GO annotations

AspectTerm
Cellular Componentendoplasmic reticulum membrane
Cellular Componentperoxisomal membrane
Molecular Functionhydroxymethylglutaryl-CoA reductase (NADPH) activity
Biological Processcoenzyme A metabolic process
Biological Processergosterol biosynthetic process
Biological Processisoprenoid biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    3-hydroxy-3-methylglutaryl coenzyme A reductase mokG
  • EC number
  • Short names
    HMG-CoA reductase
  • Alternative names
    • Monacolin K biosynthesis protein G

Gene names

    • Name
      mokG

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Monascus

Accessions

  • Primary accession
    Q3S2U3

Subcellular Location

Features

Showing features for transmembrane.

TypeIDPosition(s)Description
Transmembrane223-243Helical
Transmembrane253-273Helical
Transmembrane279-299Helical
Transmembrane349-369Helical
Transmembrane378-398Helical
Transmembrane440-460Helical

Keywords

Phenotypes & Variants

PTM/Processing

Features

Showing features for chain, glycosylation.

Type
IDPosition(s)Description
ChainPRO_00004362891-10523-hydroxy-3-methylglutaryl coenzyme A reductase mokG
Glycosylation798N-linked (GlcNAc...) asparagine
Glycosylation1043N-linked (GlcNAc...) asparagine

Keywords

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
IDPosition(s)Description
Domain224-403SSD
Region461-617Linker
Region571-594Disordered
Compositional bias574-591Pro residues
Region618-1044Catalytic

Sequence similarities

Belongs to the HMG-CoA reductase family.

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    1,052
  • Mass (Da)
    112,803
  • Last updated
    2005-10-11 v1
  • Checksum
    6BC49D73EC37A298
MASAAVTPKLGWVQHQVTNGLHAVVGQVCRHPIHTLLVTALIAATTYLHVLEGTFRAANLGPGSKTDAAPFDVQSFLWGSRSLRLGETSSWRWQVGDLSEATGDGQVNHHWALVTLSFPGASVDDRSPAFLWNALPDSVGAEPITPTSNFFTSISNEFSLAFRVPYTQLSDFLEAVEFVASDKEDRSWAIRFPHGEGKPISLGRWLGNSWLSFLHRAKHAETVDMAIIGLGYLALNMTLVSLFRAMRQLGSRFWLAASVLLSGAFAFVFGLGVTTACGVPVDMLLLSEGIPFLVLTVGFEKPIRFTRAVLYASNQLRRGLQQRDVADKHDSRQRHMIPNAMLFAINREGWSIVQSYLLEIGALALGAVFRPRERFGQFCFLAAWMVLFDAILLFTFYATILCVKLEVTRMQNPGTLDLADDQHGPRIFGYKVNPTSLARWKLIMVGGFVLFNVLQLSSFFYRIMGGFMTNAALTPTTVSPFKVAANGLNDIYLAARAGGVETWVTVLPPIRYVMEASGLEMSAGRRPVFDGVLAGLESPLGRLCLMGALVFSLYLNNHLIPAARWHFSPGAPKESAAPAPPSSPASVPSAVPVPAPSSRSFEEIEALFKANQAESLTDDELAELCLRGKIAGYSLEKTLESIASAGSSSTATTRLEAFTRAVRIRRAAVSRTPSTRDLSGGIQESLLPYRNYNYELVHGACCENVIGYLPLPLGLAGPMVIDGQAYFIPMATTEGVLVASASRGCKAINTGGGAVTMLKGDGMTRGPCLGFPSAKRAAEAQRWVESPVGHQVLTDAFNATSRFARLQTLTVAQAGTYLYIRFRTTTGDAMGMNMISKGVEKALQAMTAHGFPDMNTITLSGNFCADKKSAAINWIGGRGKSVIAEATIPADTVRKVLKTDIDALVELNTAKNLVGSAMAGSMGGFNAHASNLVQAVFLATGQDPAQNVESSSCITTMKKIDGNLHIAVSMPSMEVGTIGGGTILEAQGAMLDLLGVRGAHPTDPGANARRLARIVAAAVLAGELSTCSALAAGHLVNAHMRHNRSAASSEKK

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias574-591Pro residues

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
DQ176595
EMBL· GenBank· DDBJ
ABA02245.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

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