Database accession: MF7000493
Name: N-demethylindolmycin synthase (PluN2) with N-demethylindolmycin
PDB ID: 6p29
Experimental method: X-ray (1.50 Å)
Assembly: Homodimer
Source organism: Pseudoalteromonas luteoviolacea CPMOR-1
Primary publication of the structure:
Du YL, Higgins MA, Zhao G, Ryan KS
Convergent biosynthetic transformations to a bacterial specialized metabolite.
(2019) Nat. Chem. Biol. 15: 1043-1048
PMID: 31406372
Abstract:
Microbes produce specialized metabolites to thrive in their natural habitats. However, it is rare that a given specialized metabolite is biosynthesized via pathways with distinct intermediates and enzymes. Here, we show that the core assembly mechanism of the antibiotic indolmycin in marine gram-negative Pseudoalteromonas luteoviolacea is distinct from its counterpart in terrestrial gram-positive Streptomyces species, with a molecule that is a shunt product in the Streptomyces pathway employed as a biosynthetic substrate for a novel metal-independent N-demethylindolmycin synthase in the P. luteoviolacea pathway. To provide insight into this reaction, we solved the 1.5 Å resolution structure in complex with product and identified the active site residues. Guided by our biosynthetic insights, we then engineered the Streptomyces indolmycin producer for titer improvement. This study provides a paradigm for understanding how two unique routes to a microbial specialized metabolite can emerge from convergent biosynthetic transformations.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.Molecular function: not assigned
Biological process: not assigned
Cellular component: not assigned
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, B
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: VOC domain-containing protein
Source organism: Pseudoalteromonas luteoviolacea CPMOR-1
Length: 132 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMEFNNTIPELVCRDIDSSLSFYTHKLGFKVLFEREEQGFFFLYKNDIQLMLQQLGETAWMSHGNDTPFGNGMNIAFKVESLDDLDCSSPSEDIFLETETIEYRVLDGVASVNQVIFRDPDGYLIRFVEQVNQ
UniProtKB AC: A0A167HII1 (positions: 1-132)
Coverage: 100%
Name: VOC domain-containing protein
Source organism: Pseudoalteromonas luteoviolacea CPMOR-1
Length: 132 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMEFNNTIPELVCRDIDSSLSFYTHKLGFKVLFEREEQGFFFLYKNDIQLMLQQLGETAWMSHGNDTPFGNGMNIAFKVESLDDLDCSSPSEDIFLETETIEYRVLDGVASVNQVIFRDPDGYLIRFVEQVNQ
UniProtKB AC: A0A167HII1 (positions: 1-130)
Coverage: 98%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily
Evidence level: Indirect evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
The VOC superfamily of metalloenzymes is characterized by a three-dimensional domain-swapped arrangement of tandem βαβββ-motifs (PMID:24447055). The original gene duplication event led to the βαβββ tandem structure, which appears to require dimerization for stability. Two different forms of domain-swapped dimers may coexist in solution (PMID:12121648) in which both subunits of the homodimer participate in coordination of each metal ion and formation of the U-shaped active sites in the enzyme (PMID:24004181). The complex is predominantly dimeric in solution (gel filtration) (PMID:12121648).
Chain A:
N/A
Chain B:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download the CIF file (.cif)
Download this entry's XML file (.xml)
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