2W2D

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

Summary for 2W2D

• Entry DOI: 10.2210/pdb2w2d/pdb
• Descriptor: BOTULINUM NEUROTOXIN A LIGHT CHAIN, BOTULINUM NEUROTOXIN A HEAVY CHAIN, SULFATE ION, ... (8 entities in total)
• Functional Keywords: metalloprotease, membrane domain, protein engineering, neurotoxin, metal-binding, transmembrane, pharmaceutical, hydrolase, zinc protease, mixed alpha and beta, bont, membrane, secreted, protease
• Biological source: CLOSTRIDIUM BOTULINUM; More
• Cellular location: Botulinum neurotoxin A light chain: Secreted. Botulinum neurotoxin A heavy chain: Secreted: A5HZZ9
• Total number of polymer chains: 4
• Total formula weight: 203251.05

Authors

Masuyer, G.,Thiyagarajan, N.,James, P.L.,Marks, P.M.H.,Chaddock, J.A.,Acharya, K.R. (deposition date: 2008-10-29, release date: 2009-03-24, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.59 Å)