3ZUQ

Crystal structure of an engineered botulinum neurotoxin type B - derivative, LC-B-GS-Hn-B

Summary for 3ZUQ

• Entry DOI: 10.2210/pdb3zuq/pdb
• Related: 1EPW 1F31 1F82 1G9A 1G9B 1G9C 1G9D 1I1E 1S0B 1S0C 1S0D 1S0E 1S0F 1S0G 1Z0H 2ETF 2XHL 3ZUR 3ZUS
• Descriptor: BOTULINUM NEUROTOXIN TYPE B, ZINC ION (3 entities in total)
• Functional Keywords: hydrolase, protein engineering
• Biological source: CLOSTRIDIUM BOTULINUM
• Cellular location: Botulinum neurotoxin B light chain: Secreted. Botulinum neurotoxin B heavy chain: Secreted: P10844
• Total number of polymer chains: 1
• Total formula weight: 102842.50

Authors

Masuyer, G.,Stancombe, P.,Chaddock, J.A.,Acharya, K.R. (deposition date: 2011-07-19, release date: 2011-12-07, Last modification date: 2023-12-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.7 Å)