6N8E

Crystal structure of holo-ObiF1, a five domain nonribosomal peptide synthetase from Burkholderia diffusa

6N8E の概要

• エントリーDOI: 10.2210/pdb6n8e/pdb
• 分子名称: holo-ObiF1, 4'-PHOSPHOPANTETHEINE, dimethyl hydrogen phosphate, ... (7 entities in total)
• 機能のキーワード: nrps, beta-lactone, module, thioesterase, hydrolase
• 由来する生物種: Burkholderia diffusa
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 153266.25

構造登録者

Kreitler, D.F.,Wencewicz, T.A.,Gulick, A.M. (登録日: 2018-11-29, 公開日: 2019-07-24, 最終更新日: 2023-10-11)

主引用文献

Kreitler, D.F.,Gemmell, E.M.,Schaffer, J.E.,Wencewicz, T.A.,Gulick, A.M.
The structural basis of N-acyl-alpha-amino-beta-lactone formation catalyzed by a nonribosomal peptide synthetase.
Nat Commun, 10:3432-3432, 2019

PubMed Abstract: Nonribosomal peptide synthetases produce diverse natural products using a multidomain architecture where the growing peptide, attached to an integrated carrier domain, is delivered to neighboring catalytic domains for bond formation and modification. Investigation of these systems can lead to the discovery of new structures, unusual biosynthetic transformations, and to the engineering of catalysts for generating new products. The antimicrobial β-lactone obafluorin is produced nonribosomally from dihydroxybenzoic acid and a β-hydroxy amino acid that cyclizes into the β-lactone during product release. Here we report the structure of the nonribosomal peptide synthetase ObiF1, highlighting the structure of the β-lactone-producing thioesterase domain and an interaction between the C-terminal MbtH-like domain with an upstream adenylation domain. Biochemical assays examine catalytic promiscuity, provide mechanistic insight, and demonstrate utility for generating obafluorin analogs. These results advance our understanding of the structural cycle of nonribosomal peptide synthetases and provide insights into the production of β-lactone natural products.

PubMed: 31366889
DOI: 10.1038/s41467-019-11383-7

実験手法

X-RAY DIFFRACTION (3 Å)