9BFE

Tyrocidine synthetase modules 1 and 2 crosslinked in the condensation state, complex B

これはPDB形式変換不可エントリーです。

9BFE の概要

• エントリーDOI: 10.2210/pdb9bfe/pdb
• EMDBエントリー: 44494
• 分子名称: Tyrocidine synthase 1, Tyrocidine synthase 2, (7S,10aR)-1-methyl-4-{4-[(5R)-1,1,5-trihydroxy-4,4-dimethyl-1,6,11-trioxo-2-oxa-7,10-diaza-1lambda~5~-phosphadodecan-12-yl]phenyl}-3,5,6,7,8,9,10,10a-octahydrocycloocta[d]pyridazin-7-yl [2-({N-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-beta-alanyl}amino)ethyl]carbamate, ... (4 entities in total)
• 機能のキーワード: complex, crosslinked, nrps, isomerase
• 由来する生物種: Brevibacillus parabrevis; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 245134.01

構造登録者

Heberlig, G.W.,Burkart, M.D. (登録日: 2024-04-17, 公開日: 2024-10-09, 最終更新日: 2025-02-19)

主引用文献

Heberlig, G.W.,La Clair, J.J.,Burkart, M.D.
Crosslinking intermodular condensation in non-ribosomal peptide biosynthesis.
Nature, 638:261-269, 2025

PubMed Abstract: Non-ribosomal peptide synthetases are assembly line biosynthetic pathways that are used to produce critical therapeutic drugs and are typically arranged as large multi-domain proteins called megasynthetases. They synthesize polypeptides using peptidyl carrier proteins that shuttle each amino acid through modular loading, modification and elongation steps, and remain challenging to structurally characterize, owing in part to the inherent dynamics of their multi-domain and multi-modular architectures. Here we have developed site-selective crosslinking probes to conformationally constrain and resolve the interactions between carrier proteins and their partner enzymatic domains. We apply tetrazine click chemistry to trap the condensation of two carrier protein substrates within the active site of the condensation domain that unites the first two modules of tyrocidine biosynthesis and report the high-resolution cryo-EM structure of this complex. Together with the X-ray crystal structure of the first carrier protein crosslinked to its epimerization domain, these structures highlight captured intermodular recognition events and define the processive movement of a carrier protein from one catalytic step to the next. Characterization of these structural relationships remains central to understanding the molecular details of these unique synthetases and critically informs future synthetic biology design of these pathways.

PubMed: 39663458
DOI: 10.1038/s41586-024-08306-y

実験手法

ELECTRON MICROSCOPY (3.23 Å)