PDBsum entry 6c0h

Biosynthetic protein

PDB id: 6c0h

Contents

Protein chains

114 a.a.

108 a.a.

14 a.a.

Metals

__K ×2

Waters ×143

PDB id:

6c0h

Name:

Biosynthetic protein

Title:

Lysinoalanine synthase, durn, from duramycin biosynthesis bound to 1- dha6ala

Structure:

Lysinoalanine synthase. Chain: a, b. Engineered: yes. Gln-dal-cys-ala-phe-gly-pro-phe-dbb-phe-val-cys-bh2-gly. Chain: c. Engineered: yes

Source:

Streptomyces cinnamoneus. Organism_taxid: 53446. Atcc: 12686. Gene: durn. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Gene: dura.

Resolution:

1.90Å R-factor: 0.194 R-free: 0.251

Authors:

D.P.Cogan,S.K.Nair

Key ref:

L.An et al. (2018). Substrate-assisted enzymatic formation of lysinoalanine in duramycin. Nat Chem Biol, 14, 928-933. PubMed id: 30177849 DOI: 10.1038/s41589-018-0122-4

Date:

31-Dec-17 Release date: 05-Sep-18

Protein chain

A0A3F2YLX1  (A0A3F2YLX1_STRCJ) -  Lysinoalanine synthase from Streptomyces cinnamoneus

Seq: 121 a.a.

Struc: 114 a.a.

Protein chain

A0A3F2YLX1  (A0A3F2YLX1_STRCJ) -  Lysinoalanine synthase from Streptomyces cinnamoneus

Seq: 121 a.a.

Struc: 108 a.a.

Protein chain

A0A3F2YLX0  (A0A3F2YLX0_STRCJ) -  Gln-dal-cys-ala-phe-gly-pro-phe-dbb-phe-val-cys-bh2-gly from Streptomyces cinnamoneus

Seq: 22 a.a.

Struc: 14 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1038/s41589-018-0122-4

Nat Chem Biol 14:928-933 (2018)

PubMed id: 30177849

Substrate-assisted enzymatic formation of lysinoalanine in duramycin.

L.An, D.P.Cogan, C.D.Navo, G.Jiménez-Osés, S.K.Nair, W.A.van der Donk.

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.