7EMY

Pyochelin synthetase, a dimeric nonribosomal peptide synthetase elongation module

7EMY の概要

• エントリーDOI: 10.2210/pdb7emy/pdb
• EMDBエントリー: 31198
• 分子名称: Dihydroaeruginoic acid synthetase, 4'-PHOSPHOPANTETHEINE, 2-HYDROXYBENZOIC ACID, ... (6 entities in total)
• 機能のキーワード: nonribosomal peptide synthetase, biosynthetic protein, ligase
• 由来する生物種: Pseudomonas aeruginosa PAO1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 319503.59

構造登録者

Wang, J.L.,Wang, Z.J. (登録日: 2021-04-15, 公開日: 2021-12-22, 最終更新日: 2023-07-05)

主引用文献

Wang, J.,Li, D.,Chen, L.,Cao, W.,Kong, L.,Zhang, W.,Croll, T.,Deng, Z.,Liang, J.,Wang, Z.
Catalytic trajectory of a dimeric nonribosomal peptide synthetase subunit with an inserted epimerase domain.
Nat Commun, 13:592-592, 2022

PubMed Abstract: Nonribosomal peptide synthetases (NRPSs) are modular assembly-line megaenzymes that synthesize diverse metabolites with wide-ranging biological activities. The structural dynamics of synthetic elongation has remained unclear. Here, we present cryo-EM structures of PchE, an NRPS elongation module, in distinct conformations. The domain organization reveals a unique "H"-shaped head-to-tail dimeric architecture. The capture of both aryl and peptidyl carrier protein-tethered substrates and intermediates inside the heterocyclization domain and L-cysteinyl adenylate in the adenylation domain illustrates the catalytic and recognition residues. The multilevel structural transitions guided by the adenylation C-terminal subdomain in combination with the inserted epimerase and the conformational changes of the heterocyclization tunnel are controlled by two residues. Moreover, we visualized the direct structural dynamics of the full catalytic cycle from thiolation to epimerization. This study establishes the catalytic trajectory of PchE and sheds light on the rational re-engineering of domain-inserted dimeric NRPSs for the production of novel pharmaceutical agents.

PubMed: 35105906
DOI: 10.1038/s41467-022-28284-x

実験手法

ELECTRON MICROSCOPY (2.97 Å)