1ZKX

Crystal structure of Glu158Ala/Thr159Ala/Asn160Ala- a triple mutant of Clostridium botulinum neurotoxin E catalytic domain

1ZKX の概要

• エントリーDOI: 10.2210/pdb1zkx/pdb
• 関連するPDBエントリー: 1T3A 1T3C 1ZKW 1ZL5 1ZL6
• 分子名称: botulinum neurotoxin type E, ZINC ION, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: botulinum neurotoxin e, catalytic domain, light chain, glu158ala/thr159ala/asn160ala mutant, hydrolase
• 由来する生物種: Clostridium botulinum
• 細胞内の位置: Botulinum neurotoxin E light chain: Secreted. Botulinum neurotoxin E heavy chain: Secreted: Q00496
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 95386.03

構造登録者

Agarwal, R.,Binz, T.,Swaminathan, S. (登録日: 2005-05-04, 公開日: 2005-07-05, 最終更新日: 2023-08-23)

主引用文献

Agarwal, R.,Binz, T.,Swaminathan, S.
Analysis of Active Site Residues of Botulinum Neurotoxin E by Mutational, Functional, and Structural Studies: Glu335Gln Is an Apoenzyme.
Biochemistry, 44:8291-8302, 2005

PubMed Abstract: Clostridial neurotoxins comprising the seven serotypes of botulinum neurotoxins and tetanus neurotoxin are the most potent toxins known to humans. Their potency coupled with their specificity and selectivity underscores the importance in understanding their mechanism of action in order to develop a strategy for designing counter measures against them. To develop an effective vaccine against the toxin, it is imperative to achieve an inactive form of the protein which preserves the overall conformation and immunogenicity. Inactive mutants can be achieved either by targeting active site residues or by modifying the surface charges farther away from the active site. The latter affects the long-range forces such as electrostatic potentials in a subtle way without disturbing the structural integrity of the toxin causing some drastic changes in the activity/environment. Here we report structural and biochemical analysis on several mutations on Clostridium botulinum neurotoxin type E light chain with at least two producing dramatic effects: Glu335Gln causes the toxin to transform into a persistent apoenzyme devoid of zinc, and Tyr350Ala has no hydrolytic activity. The structural analysis of several mutants has led to a better understanding of the catalytic mechanism of this family of proteins. The residues forming the S1' subsite have been identified by comparing this structure with a thermolysin-inhibitor complex structure.

PubMed: 15938619
DOI: 10.1021/bi050253a

実験手法

X-RAY DIFFRACTION (2.52 Å)