2W2D

Crystal Structure of a Catalytically Active, Non-toxic Endopeptidase Derivative of Clostridium botulinum Toxin A

2W2D の概要

• エントリーDOI: 10.2210/pdb2w2d/pdb
• 分子名称: BOTULINUM NEUROTOXIN A LIGHT CHAIN, BOTULINUM NEUROTOXIN A HEAVY CHAIN, SULFATE ION, ... (8 entities in total)
• 機能のキーワード: metalloprotease, membrane domain, protein engineering, neurotoxin, metal-binding, transmembrane, pharmaceutical, hydrolase, zinc protease, mixed alpha and beta, bont, membrane, secreted, protease
• 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: A5HZZ9
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 203251.05

構造登録者

Masuyer, G.,Thiyagarajan, N.,James, P.L.,Marks, P.M.H.,Chaddock, J.A.,Acharya, K.R. (登録日: 2008-10-29, 公開日: 2009-03-24, 最終更新日: 2024-10-16)

主引用文献

Masuyer, G.,Thiyagarajan, N.,James, P.L.,Marks, P.M.H.,Chaddock, J.A.,Acharya, K.R.
Crystal Structure of a Catalytically Active, Non-Toxic Endopeptidase Derivative of Clostridium Botulinum Toxin A.
Biochem.Biophys.Res.Commun., 381:50-, 2009

PubMed Abstract: Botulinum neurotoxins (BoNTs) modulate cholinergic nerve terminals to result in neurotransmitter blockade. BoNTs consists of catalytic (LC), translocation (Hn) and cell-binding domains (Hc). The binding function of the Hc domain is essential for BoNTs to bind the neuronal cell membrane, therefore, removal of the Hc domain results in a product that retains the endopeptidase activity of the LC but is non-toxic. Thus, a molecule consisting of LC and Hn domains of BoNTs, termed LHn, is a suitable molecule for engineering novel therapeutics. The structure of LHA at 2.6 A reported here provides an understanding of the structural implications and challenges of engineering therapeutic molecules that combine functional properties of LHn of BoNTs with specific ligand partners to target different cell types.

PubMed: 19351593
DOI: 10.1016/J.BBRC.2009.02.003

実験手法

X-RAY DIFFRACTION (2.59 Å)