Database accession: MF7001004
Name: Lysinoalanine synthase, DurN
PDB ID: 6c0g
Experimental method: X-ray (2.15 Å)
Assembly: Homodimer
Source organism: Streptomyces cinnamoneus
Primary publication of the structure:
An L, Cogan DP, Navo CD, Jiménez-Osés G, Nair SK, van der Donk WA
Substrate-assisted enzymatic formation of lysinoalanine in duramycin.
(2018) Nat. Chem. Biol. 14: 928-933
PMID: 30177849
Abstract:
Duramycin is a heavily post-translationally modified peptide that binds phosphatidylethanolamine. It has been investigated as an antibiotic, an inhibitor of viral entry, a therapeutic for cystic fibrosis, and a tumor and vasculature imaging agent. Duramycin contains a β-hydroxylated Asp (Hya) and four macrocycles, including an essential lysinoalanine (Lal) cross-link. The mechanism of Lal formation is not known. Here we show that Lal is installed stereospecifically by DurN via addition of Lys19 to a dehydroalanine. The structure of DurN reveals an unusual dimer with a new fold. Surprisingly, in the structure of duramycin bound to DurN, no residues of the enzyme are near the Lal cross-link. Instead, Hya15 of the substrate makes interactions with Lal, suggesting it acts as a base to deprotonate Lys19 during catalysis. Biochemical data suggest that DurN preorganizes the reactive conformation of the substrate, such that the Hya15 of the substrate can serve as the catalytic base for Lal formation.
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-2
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: Lysinoalanine synthase
Source organism: Streptomyces cinnamoneus
Length: 121 residues
Sequence:Sequence according to the corresponding UniProt protein segmentSGMKSAKEPTIYQDVDIIRRIQELMVLCSLLPPDGKLREALELALALHEEPALARITPLTNLHPFATKAWLETLWLGEGVSSEEKELVAWQNKSENMGPAIRELKNAEQQSGITLVARLTS
UniProtKB AC: A0A3F2YLX1 (positions: 8-121)
Coverage: 94%
Name: Lysinoalanine synthase
Source organism: Streptomyces cinnamoneus
Length: 121 residues
Sequence:Sequence according to the corresponding UniProt protein segmentSGMKSAKEPTIYQDVDIIRRIQELMVLCSLLPPDGKLREALELALALHEEPALARITPLTNLHPFATKAWLETLWLGEGVSSEEKELVAWQNKSENMGPAIRELKNAEQQSGITLVARLTS
UniProtKB AC: A0A3F2YLX1 (positions: 8-121)
Coverage: 94%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: -
Evidence level: Insufficient evidence (candidate)
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
The overall structure of DurN consists of an interlaced homodimer where helix α1 is engaged with residues from helices α2–α6 in the adjacent monomer. An intermolecular, antiparallel β-strand is also formed between the monomers (PMID:30177849).
Chain A:
N/A
Chain B-2:
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). No related structure was found in the MFIB database.
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