2A97

Crystal structure of catalytic domain of Clostridium botulinum neurotoxin serotype F

Summary for 2A97

• Entry DOI: 10.2210/pdb2a97/pdb
• Related: 2A8A
• Descriptor: Botulinum neurotoxin type F, ZINC ION, CADMIUM ION, ... (4 entities in total)
• Functional Keywords: clostridium botulinum neurotoxin serotype f; light chain; catalytic domain; x-ray; crystal structure; zinc endopeptidase, hydrolase
• Biological source: Clostridium botulinum
• Cellular location: Botulinum neurotoxin F light chain: Secreted. Botulinum neurotoxin F heavy chain: Secreted: P30996
• Total number of polymer chains: 2
• Total formula weight: 100828.34

Authors

Agarwal, R.,Binz, T.,Swaminathan, S. (deposition date: 2005-07-11, release date: 2005-09-20, Last modification date: 2023-08-23)

Primary citation

Agarwal, R.,Binz, T.,Swaminathan, S.
Structural analysis of botulinum neurotoxin serotype f light chain: implications on substrate binding and inhibitor design
Biochemistry, 44:11758-11765, 2005

PubMed Abstract: The seven serologically distinct Clostridium botulinum neurotoxins (BoNTs A-G) are zinc endopeptidases which block the neurotransmitter release by cleaving one of the three proteins of the soluble N-ethylmaleimide-sensitive-factor attachment protein receptor complex (SNARE complex) essential for the fusion of vesicles containing neurotransmitters with target membranes. These metallopeptidases exhibit unique specificity for the substrates and peptide bonds they cleave. Development of countermeasures and therapeutics for BoNTs is a priority because of their extreme toxicity and potential misuse as biowarfare agents. Though they share sequence homology and structural similarity, the structural information on each one of them is required to understand the mechanism of action of all of them because of their specificity. Unraveling the mechanism will help in the ultimate goal of developing inhibitors as antibotulinum drugs for the toxins. Here, we report the high-resolution structure of active BoNT/F catalytic domain in two crystal forms. The structure was exploited for modeling the substrate binding and identifying the S1' subsite and the putative exosites which are different from BoNT/A or BoNT/B. The orientation of docking of the substrate at the active site is consistent with the experimental BoNT/A-LC:SNAP-25 peptide model and our proposed model for BoNT/E-LC:SNAP-25.

PubMed: 16128577
DOI: 10.1021/bi0510072

Experimental method

X-RAY DIFFRACTION (1.8 Å)