5ES8

Crystal structure of the initiation module of LgrA in the thiolation state

5ES8 の概要

• エントリーDOI: 10.2210/pdb5es8/pdb
• 関連するPDBエントリー: 5ES5 5ES6 5ES7 5ES9
• 分子名称: Linear gramicidin synthetase subunit A, [(3~{R})-4-[[3-[2-[[(2~{S})-2-azanyl-3-methyl-butanoyl]amino]ethylamino]-3-oxidanylidene-propyl]amino]-2,2-dimethyl-3-oxidanyl-4-oxidanylidene-butyl] dihydrogen phosphate (3 entities in total)
• 機能のキーワード: nrps, formylation domain, adenylation domain, peptidyl carrier protein, ligase
• 由来する生物種: Brevibacillus parabrevis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 177007.22

構造登録者

Reimer, J.M.,Aloise, M.N.,Schmeing, T.M. (登録日: 2015-11-16, 公開日: 2016-01-20, 最終更新日: 2024-11-13)

主引用文献

Reimer, J.M.,Aloise, M.N.,Harrison, P.M.,Schmeing, T.M.
Synthetic cycle of the initiation module of a formylating nonribosomal peptide synthetase.
Nature, 529:239-242, 2016

PubMed Abstract: Nonribosomal peptide synthetases (NRPSs) are very large proteins that produce small peptide molecules with wide-ranging biological activities, including environmentally friendly chemicals and many widely used therapeutics. NRPSs are macromolecular machines, with modular assembly-line logic, a complex catalytic cycle, moving parts and many active sites. In addition to the core domains required to link the substrates, they often include specialized tailoring domains, which introduce chemical modifications and allow the product to access a large expanse of chemical space. It is still unknown how the NRPS tailoring domains are structurally accommodated into megaenzymes or how they have adapted to function in nonribosomal peptide synthesis. Here we present a series of crystal structures of the initiation module of an antibiotic-producing NRPS, linear gramicidin synthetase. This module includes the specialized tailoring formylation domain, and states are captured that represent every major step of the assembly-line synthesis in the initiation module. The transitions between conformations are large in scale, with both the peptidyl carrier protein domain and the adenylation subdomain undergoing huge movements to transport substrate between distal active sites. The structures highlight the great versatility of NRPSs, as small domains repurpose and recycle their limited interfaces to interact with their various binding partners. Understanding tailoring domains is important if NRPSs are to be utilized in the production of novel therapeutics.

PubMed: 26762462
DOI: 10.1038/nature16503

実験手法

X-RAY DIFFRACTION (2.547 Å)