G3XUF0 · MLFA_ASPNA

Function

function

Nonribosomal peptide synthetase; part of the gene cluster that mediates the biosynthesis of malformins, cyclic pentapeptides with a disulfide bond between 2 consecutive cysteins, that show potential anti-tumor as well as antimalarial and antitrypanosomal properties (PubMed:30560908).
The nonribosomal peptide synthetase mlfA is responsible of the formation of the cyclic pentapeptide (Probable). The malformin biosynthesis clusters in malformin-producing fungi also contain enzymes involved in the formation of the disulfide bond between the two consecutive cysteins within malformins, in addition to additional tailoring enzymes such as methyltransferases or oxidoreductases. They are also composed of up to 4 major facilitator superfamily transporters, and transcription factors probably involved in the regulation of the expression of those clusters (Probable)

Biotechnology

Malformins show anti-tumor properties against human colorectal and prostate cancer cells by the inhibition of proliferation and induction of apoptosis through the activation of the p38 signaling pathway (PubMed:26540166, PubMed:26645406, PubMed:28713983).
Malformin C has also been shown to exhibit potent antimalarial and antitrypanosomal properties (PubMed:19876076).

Pathway

Secondary metabolite biosynthesis.

GO annotations

AspectTerm
Molecular Functionligase activity
Molecular Functionphosphopantetheine binding

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Malformin synthetase mlfA
  • EC number
  • Alternative names
    • Malformin biosynthesis cluster protein A
    • Nonribosomal peptide synthetase mlfA

Gene names

    • Name
      mlfA
    • ORF names
      ASPNIDRAFT_43807

Organism names

Accessions

  • Primary accession
    G3XUF0

Proteomes

Phenotypes & Variants

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00004464351-4870Malformin synthetase mlfA
Modified residue672O-(pantetheine 4'-phosphoryl)serine
Modified residue1725O-(pantetheine 4'-phosphoryl)serine
Modified residue2901O-(pantetheine 4'-phosphoryl)serine
Modified residue4448O-(pantetheine 4'-phosphoryl)serine

Keywords

Interaction

Protein-protein interaction databases

Structure

3D structure databases

Family & Domains

Features

Showing features for region, domain, compositional bias.

TypeIDPosition(s)Description
Region106-497Adenylation 1
Domain635-711Carrier 1
Region749-1133Condensation 1
Region1161-1550Adenylation 2
Domain1688-1765Carrier 2
Region1764-1794Disordered
Compositional bias1766-1789Polar residues
Compositional bias1829-1852Polar residues
Region1829-1859Disordered
Region1898-2313Condensation 2
Region2336-2728Adenylation 3
Domain2864-2940Carrier 3
Region2957-3422Condensation 3
Region3443-3862Condensation 4
Region3887-4277Adenylation 4
Domain4411-4487Carrier 4
Region4524-4837Condensation 5

Domain

NRP synthetases are composed of discrete domains (adenylation (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation (C) domains) which when grouped together are referred to as a single module. Each module is responsible for the recognition (via the A domain) and incorporation of a single amino acid into the growing peptide product. Thus, an NRP synthetase is generally composed of one or more modules and can terminate in a thioesterase domain (TE) that releases the newly synthesized peptide from the enzyme. Occasionally, epimerase (E) domains (responsible for L- to D- amino acid conversion) are present within the NRP synthetase. MlfA has the following architecture: A-T-C-A-T-C-A-T-C-C-A-T-C, with the functions of the five condensation domains during malformin biosynthesis being DL-joining (epimerizing subtype), LL-joining, epimerization, DL-joining and cyclizing domain, respectively.

Sequence similarities

Belongs to the NRP synthetase family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    4,870
  • Mass (Da)
    535,293
  • Last updated
    2011-12-14 v1
  • Checksum
    9BDDCA217490CA0C

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias1766-1789Polar residues
Compositional bias1829-1852Polar residues

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
ACJE01000005
EMBL· GenBank· DDBJ
EHA25778.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

Disclaimer

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