2N6Y

Solution structure of holo ArCP from yersiniabactin synthetase

2N6Y の概要

• エントリーDOI: 10.2210/pdb2n6y/pdb
• 関連するPDBエントリー: 2N6Z
• NMR情報: BMRB: 25786
• 分子名称: HMWP2 nonribosomal peptide synthetase (1 entity in total)
• 機能のキーワード: carrier protein, holo, nonribosomal peptide synthetase, yersiniabactin, ligase
• 由来する生物種: Yersinia pestis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10111.40

構造登録者

Goodrich, A.C.,Harden, B.J.,Frueh, D.P. (登録日: 2015-08-31, 公開日: 2015-09-23, 最終更新日: 2015-10-07)

主引用文献

Goodrich, A.C.,Harden, B.J.,Frueh, D.P.
Solution Structure of a Nonribosomal Peptide Synthetase Carrier Protein Loaded with Its Substrate Reveals Transient, Well-Defined Contacts.
J.Am.Chem.Soc., 137:12100-12109, 2015

PubMed Abstract: Nonribosomal peptide synthetases (NRPSs) are microbial enzymes that produce a wealth of important natural products by condensing substrates in an assembly line manner. The proper sequence of substrates is obtained by tethering them to phosphopantetheinyl arms of holo carrier proteins (CPs) via a thioester bond. CPs in holo and substrate-loaded forms visit NRPS catalytic domains in a series of transient interactions. A lack of structural information on substrate-loaded carrier proteins has hindered our understanding of NRPS synthesis. Here, we present the first structure of an NRPS aryl carrier protein loaded with its substrate via a native thioester bond, together with the structure of its holo form. We also present the first quantification of NRPS CP backbone dynamics. Our results indicate that prosthetic moieties in both holo and loaded forms are in contact with the protein core, but they also sample states in which they are disordered and extend in solution. We observe that substrate loading induces a large conformational change in the phosphopantetheinyl arm, thereby modulating surfaces accessible for binding to other domains. Our results are discussed in the context of NRPS domain interactions.

PubMed: 26334259
DOI: 10.1021/jacs.5b07772

実験手法

SOLUTION NMR