1G9C

CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN B COMPLEXED WITH AN INHIBITOR (EXPERIMENT 4)

1G9C の概要

• エントリーDOI: 10.2210/pdb1g9c/pdb
• 関連するPDBエントリー: 1EPW 1F31
• 分子名称: BOTULINUM NEUROTOXIN TYPE B, ZINC ION, BIS(5-AMIDINO-BENZIMIDAZOLYL)METHANE, ... (4 entities in total)
• 機能のキーワード: botulinum, neurotoxin, inhibitor, complex, hydrolase
• 由来する生物種: Clostridium botulinum
• 細胞内の位置: Botulinum neurotoxin B light chain: Secreted. Botulinum neurotoxin B heavy chain: Secreted: P10844
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 151634.96

構造登録者

Eswaramoorthy, S.,Swaminathan, S. (登録日: 2000-11-22, 公開日: 2002-11-13, 最終更新日: 2024-10-30)

主引用文献

Eswaramoorthy, S.,Kumaran, D.,Swaminathan, S.
A Novel Mechanism for Clostridium botulinum Neurotoxin Inhibition
BIOCHEMISTRY, 41:9795-9802, 2002

PubMed Abstract: Clostridium botulinum neurotoxins are zinc endopeptidase proteins responsible for cleaving specific peptide bonds of proteins of neuroexocytosis apparatus. The ability of drugs to interfere with toxin's catalytic activity is being evaluated with zinc chelators and metalloprotease inhibitors. It is important to develop effective pharmacological treatment for the intact holotoxin before the catalytic domain separates and enters the cytosol. We present here evidence for a novel mechanism of an inhibitor binding to the holotoxin and for the chelation of zinc from our structural studies on Clostridium botulinum neurotoxin type B in complex with a potential metalloprotease inhibitor, bis(5-amidino-2-benzimidazolyl)methane, and provide snapshots of the reaction as it progresses. The binding and inhibition mechanism of this inhibitor to the neurotoxin seems to be unique for intact botulinum neurotoxins. The environment of the active site rearranges in the presence of the inhibitor, and the zinc ion is gradually removed from the active site and transported to a different site in the protein, probably causing loss of catalytic activity.

PubMed: 12146945
DOI: 10.1021/bi020060c

実験手法

X-RAY DIFFRACTION (2.35 Å)