5BQM

Crystal structure of SXN101959, a Clostridium botulinum neurotoxin type D derivative and targeted secretion inhibitor

5BQM の概要

• エントリーDOI: 10.2210/pdb5bqm/pdb
• 分子名称: Botulinum neurotoxin type D, Somatoliberin,Botulinum neurotoxin type D, ZINC ION, ... (4 entities in total)
• 機能のキーワード: botulinum neurotoxin, targeted secretion inhibitors, endopeptidase, type d, protein engineering, hydrolase
• 由来する生物種: Clostridium botulinum; 詳細
• 細胞内の位置: Botulinum neurotoxin D light chain: Secreted. Botulinum neurotoxin D heavy chain: Secreted: P19321 P19321
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 210922.22

構造登録者

Masuyer, G.,Davies, J.R.,Moore, K.,Chaddock, J.A.,Acharya, K.R. (登録日: 2015-05-29, 公開日: 2015-08-19, 最終更新日: 2024-11-20)

主引用文献

Masuyer, G.,Davies, J.R.,Moore, K.,Chaddock, J.A.,Ravi Acharya, K.
Structural analysis of Clostridium botulinum neurotoxin type D as a platform for the development of targeted secretion inhibitors.
Sci Rep, 5:13397-13397, 2015

PubMed Abstract: The botulinum neurotoxin type D is one of seven highly potent toxins produced by Clostridium botulinum which inhibit neurotransmission at cholinergic nerve terminals. A functional fragment derived from the toxin, LHn, consisting of the catalytic and translocation domains, has been heralded as a platform for the development of targeted secretion inhibitors. These secretion inhibitors are aimed at retargeting the toxin towards a specific cell type to inhibit vesicular secretion. Here we report crystal structures of LHn from serotype D at 2.3 Å, and that of SXN101959 at 3.1 Å resolution. SXN101959, a derivative that combines LHn from serotype D with a fragment of the growth hormone releasing hormone, has previously revealed promising results in inhibiting growth hormone release in pituitary somatotrophs. These structures offer for the first time insights into the translocation domain interaction with the catalytic domain in serotype D. Furthermore, structural information from small-angle X-ray scattering of LHn/D is compared among serotypes A, B, and D. Taken together, these results demonstrate the robustness of the 'LHn fold' across serotypes and its use in engineering additional polypeptide components with added functionality. Our study demonstrates the suitability of botulinum neurotoxin, and serotype D in particular, as a basis for engineering novel secretion inhibitors.

PubMed: 26324071
DOI: 10.1038/srep13397

実験手法

X-RAY DIFFRACTION (3.1 Å)