3ZUR

Crystal structure of an engineered botulinum neurotoxin type A- SNARE23 derivative, LC0-A-SNAP25-Hn-A

3ZUR の概要

• エントリーDOI: 10.2210/pdb3zur/pdb
• 関連するPDBエントリー: 1KIL 1UEE 1XTF 1XTG 2VU9 2VUA 2W2D 3BTA 3ZUQ 3ZUS
• 分子名称: BOTULINUM NEUROTOXIN TYPE A, SYNAPTOSOMAL-ASSOCIATED PROTEIN, SULFATE ION (3 entities in total)
• 機能のキーワード: hydrolase-signaling protein complex, hydrolase, snare, protein engineering, hydrolase/signaling protein
• 由来する生物種: CLOSTRIDIUM BOTULINUM; 詳細
• 細胞内の位置: Botulinum neurotoxin A light chain: Secreted. Botulinum neurotoxin A heavy chain: Secreted: P10845
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 217620.30

構造登録者

Masuyer, G.,Stancombe, P.,Chaddock, J.A.,Acharya, K.R. (登録日: 2011-07-19, 公開日: 2011-12-07, 最終更新日: 2024-11-06)

主引用文献

Masuyer, G.,Stancombe, P.,Chaddock, J.A.,Acharya, K.R.
Structures of Engineered Clostridium Botulinum Neurotoxin Derivatives
Acta Crystallogr.,Sect.F, 67:1466-, 2011

PubMed Abstract: Targeted secretion inhibitors (TSIs) are a new class of engineered biopharmaceutical molecules derived from the botulinum neurotoxins (BoNTs). They consist of the metalloprotease light chain (LC) and translocation domain (Hn) of BoNT; they thus lack the native toxicity towards motor neurons but are able to target soluble N-ethylmaleimide-sensitive fusion protein attachment receptor (SNARE) proteins. These functional fragment (LHn) derivatives are expressed as single-chain proteins and require post-translational activation into di-chain molecules for function. A range of BoNT derivatives have been produced to demonstrate the successful use of engineered SNARE substrate peptides at the LC-Hn interface that gives these molecules self-activating capabilities. Alternatively, recognition sites for specific exoproteases can be engineered to allow controlled activation. Here, the crystal structures of three LHn derivatives are reported between 2.7 and 3.0 Å resolution. Two of these molecules are derivatives of serotype A that contain a SNARE peptide. Additionally, a third structure corresponds to LHn serotype B that includes peptide linkers at the exoprotease activation site. In all three cases the added engineered segments could not be modelled owing to disorder. However, these structures highlight the strong interactions holding the LHn fold together despite the inclusion of significant polypeptide sequences at the LC-Hn interface.

PubMed: 22139146
DOI: 10.1107/S1744309111034671

実験手法

X-RAY DIFFRACTION (2.71 Å)