E1ACR1 · NOTP_ASPSM

Function

function

Lactamase-like protein; part of the gene cluster that mediates the biosynthesis of notoamide, a fungal indole alkaloid that belongs to a family of natural products containing a characteristic bicyclo[2.2.2]diazaoctane core (PubMed:20722388).
The first step of notoamide biosynthesis involves coupling of L-proline and L-tryptophan by the bimodular NRPS notE, to produce cyclo-L-tryptophan-L-proline called brevianamide F (PubMed:20722388).
The reverse prenyltransferase notF then acts as a deoxybrevianamide E synthase and converts brevianamide F to deoxybrevianamide E via reverse prenylation at C-2 of the indole ring leading to the bicyclo[2.2.2]diazaoctane core (PubMed:20722388).
Deoxybrevianamide E is further hydroxylated at C-6 of the indole ring, likely catalyzed by the cytochrome P450 monooxygenase notG, to yield 6-hydroxy-deoxybrevianamide E (Probable). 6-hydroxy-deoxybrevianamide E is a specific substrate of the prenyltransferase notC for normal prenylation at C-7 to produce 6-hydroxy-7-prenyl-deoxybrevianamide, also called notoamide S (PubMed:20722388).
As the proposed pivotal branching point in notoamide biosynthesis, notoamide S can be diverted to notoamide E through an oxidative pyran ring closure putatively catalyzed by either notH cytochrome P450 monooxygenase or the notD FAD-linked oxidoreductase (Probable). This step would be followed by an indole 2,3-epoxidation-initiated pinacol-like rearrangement catalyzed by the notB FAD-dependent monooxygenase leading to the formation of notoamide C and notoamide D (PubMed:22188465).
On the other hand notoamide S is converted to notoamide T by notH (or notD), a bifunctional oxidase that also functions as the intramolecular Diels-Alderase responsible for generation of +-notoamide T (Probable). To generate antipodal --notoaminide T, notH' (or notD') in Aspergillus versicolor is expected to catalyze a Diels-Alder reaction leading to the opposite stereochemistry (Probable). The remaining oxidoreductase notD (or notH) likely catalyzes the oxidative pyran ring formation to yield +-stephacidin A (Probable). The FAD-dependent monooxygenase notI is highly similar to notB and is predicted to catalyze a similar conversion from +-stephacidin A to --notoamide B via the 2,3-epoxidation of +-stephacidin A followed by a pinacol-type rearrangement (Probable). Finally, it remains unclear which enzyme could be responsible for the final hydroxylation steps leading to notoamide A and sclerotiamide (Probable). The function of notP in the notoamide biosynthesis has not been determined yet (Probable).

Cofactor

Zn2+ (UniProtKB | Rhea| CHEBI:29105 )

Note: Binds 2 Zn2+ ions per subunit.

Biotechnology

Notoamides have been shown to exhibit antitumoral activities (PubMed:17304611).
Notoamides A-C show moderate cytotoxicity against HeLa and L1210 cells with IC50 values in the range of 22-52 mg/ml, but the IC50 value of notoamide D is greater than 100 mg/ml (PubMed:17304611).
Moreover, notoamide C induces G2/M-cell cycle arrest at a concentration of 6.3 mg/ml (PubMed:17304611).

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site108Zn2+ 1 (UniProtKB | ChEBI); catalytic
Binding site110Zn2+ 1 (UniProtKB | ChEBI); catalytic
Active site112Proton donor/acceptor
Binding site112Zn2+ 2 (UniProtKB | ChEBI); catalytic
Binding site113Zn2+ 2 (UniProtKB | ChEBI); catalytic

GO annotations

AspectTerm
Molecular Functionhydrolase activity
Molecular Functionmetal ion binding
Biological Processsecondary metabolite biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Lactamase-like protein notP
  • EC number
  • Alternative names
    • Notoamide biosynthesis cluster protein P

Gene names

    • Name
      notP

Organism names

  • Taxonomic identifier
  • Strain
    • MF297-2
  • Taxonomic lineage
    Eukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Aspergillus

Accessions

  • Primary accession
    E1ACR1

Phenotypes & Variants

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004488251-321Lactamase-like protein notP

Structure

Family & Domains

Sequence similarities

Belongs to the metallo-beta-lactamase superfamily.

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    321
  • Mass (Da)
    35,451
  • Last updated
    2010-11-02 v1
  • Checksum
    7E4861981F501196
MAPGEGGYRQINKALNICAFEDYLEGQQKALPSLPDVEQISPRVLRVLGQNPASHCKFTLQGTNTFVVGTGPERLIVDTGQGIPEWADLIHETLARRGITLSHVLLTHWHGDHTGGVPDLIRMYPHLSSAIYKHEPSKTQQPITDGQIFRVEGATVRAVHTPGHSSDHMCFVLEEEHGMFTGDNILGHGTSAVEHLSTWMHTLYKMQAQDCTTGYPAHGIVISNLRTKIKGELAQKLQRERQVLKALVQAKQAERARMERAKGSVTVKELVATMYGNGVGAGIRELALEPFMDEVLRKLAEDGAVAFEVRGRVKKWFAPDA

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
HM622670
EMBL· GenBank· DDBJ
ADM34149.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

Disclaimer

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