3NF3

Crystal structure of BoNT/A LC with JTH-NB-7239 peptide

3NF3 の概要

• エントリーDOI: 10.2210/pdb3nf3/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000997
• 分子名称: BoNT/A, JTH-NB72-39 inhibitor, ZINC ION, ... (5 entities in total)
• 機能のキーワード: botulinum neurotoxin, snare, botulism, inhibition, metalloprotease, neurotransmission, neuromuscular junction, hydrolase, membrane, metal-binding, protease, secreted, toxin, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Clostridium botulinum
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49779.36

構造登録者

Zuniga, J.E. (登録日: 2010-06-09, 公開日: 2010-07-21, 最終更新日: 2023-11-22)

主引用文献

Zuniga, J.E.,Hammill, J.T.,Drory, O.,Nuss, J.E.,Burnett, J.C.,Gussio, R.,Wipf, P.,Bavari, S.,Brunger, A.T.
Iterative structure-based peptide-like inhibitor design against the botulinum neurotoxin serotype A.
Plos One, 5:e11378-e11378, 2010

PubMed Abstract: The botulinum neurotoxin serotype A light chain (BoNT/A LC) protease is the catalytic component responsible for the neuroparalysis that is characteristic of the disease state botulism. Three related peptide-like molecules (PLMs) were designed using previous information from co-crystal structures, synthesized, and assayed for in vitro inhibition against BoNT/A LC. Our results indicate these PLMS are competitive inhibitors of the BoNT/A LC protease and their K(i) values are in the nM-range. A co-crystal structure for one of these inhibitors was determined and reveals that the PLM, in accord with the goals of our design strategy, simultaneously involves both ionic interactions via its P1 residue and hydrophobic contacts by means of an aromatic group in the P2' position. The PLM adopts a helical conformation similar to previously determined co-crystal structures of PLMs, although there are also major differences to these other structures such as contacts with specific BoNT/A LC residues. Our structure further demonstrates the remarkable plasticity of the substrate binding cleft of the BoNT/A LC protease and provides a paradigm for iterative structure-based design and development of BoNT/A LC inhibitors.

PubMed: 20614028
DOI: 10.1371/journal.pone.0011378

実験手法

X-RAY DIFFRACTION (2.4 Å)