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Crystal Structure of a Catalytically Active, Non-Toxic Endopeptidase Derivative of Clostridium Botulinum Toxin A

DOI: 10.1016/j.bbrc.2009.02.003 DOI Help
PMID: 19351593 PMID Help

Authors: Geoffrey Masuyer (University of Bath) , Nethaji Thiyagarajan (University of Bath) , Peter James (Syntaxin Limited) , Philip Marks (Syntaxin Limited) , John Chaddock (Syntaxin Limited) , Ravi Acharya (University of Bath)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Biochemical And Biophysical Research Communications , VOL 381 (1) , PAGES 50-53

State: Published (Approved)
Published: February 2009

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 Å 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.

Journal Keywords: Botulinum neurotoxin; Protein engineering; Crystal structure; Therapeutics; Fusion

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography

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