6C0Y

Lysinoalanine synthase, DurN, from duramycin biosynthesis bound to duramycin

6C0Y の概要

• エントリーDOI: 10.2210/pdb6c0y/pdb
• 関連するBIRD辞書のPRD_ID: PRD_002295
• 分子名称: Lysinoalanine synthase, CYS-LYS-GLN-DAL-CYS-ALA-PHE-GLY-PRO-PHE-DBB-PHE-VAL-CYS-BH2-GLY-ASN-DBB-LYS, POTASSIUM ION, ... (4 entities in total)
• 機能のキーワード: lysinoalanine synthase, michael addition, biosynthetic protein
• 由来する生物種: Streptomyces cinnamoneus; 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 124295.64

構造登録者

Cogan, D.P.,Nair, S.K. (登録日: 2018-01-03, 公開日: 2018-09-05, 最終更新日: 2024-11-13)

主引用文献

An, L.,Cogan, D.P.,Navo, C.D.,Jimenez-Oses, G.,Nair, S.K.,van der Donk, W.A.
Substrate-assisted enzymatic formation of lysinoalanine in duramycin.
Nat. Chem. Biol., 14:928-933, 2018

PubMed 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.

PubMed: 30177849
DOI: 10.1038/s41589-018-0122-4

実験手法

X-RAY DIFFRACTION (1.66 Å)