3FIE

Crystal structure of Clostridium botulinum neurotoxin serotype F catalytic domain with an inhibitor (inh1)

Summary for 3FIE

• Entry DOI: 10.2210/pdb3fie/pdb
• Related: 2A8A 2A97 3FII
• Descriptor: BOTULINUM NEUROTOXIN TYPE F, fragment of Vesicle-associated membrane protein 2, ZINC ION, ... (4 entities in total)
• Functional Keywords: clostridium botulinum, bont f, vamp, inhibitor, complex structure, acetylation, cell junction, hydrolase, toxin-protein transport complex, toxin/protein transport
• Biological source: Clostridium botulinum; More
• Cellular location: Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Single-pass type IV membrane protein: P63027
• Total number of polymer chains: 4
• Total formula weight: 106183.74

Authors

Agarwal, R.,Swaminathan, S. (deposition date: 2008-12-11, release date: 2009-06-23, Last modification date: 2024-11-27)

Primary citation

Agarwal, R.,Schmidt, J.J.,Stafford, R.G.,Swaminathan, S.
Mode of VAMP substrate recognition and inhibition of Clostridium botulinum neurotoxin F.
Nat.Struct.Mol.Biol., 16:789-794, 2009

PubMed Abstract: Clostridium botulinum neurotoxins (BoNTs) cleave neuronal proteins responsible for neurotransmitter release, causing the neuroparalytic disease botulism. BoNT serotypes B, D, F and G cleave and inactivate vesicle-associated membrane protein (VAMP), each at a unique peptide bond. The specificity of BoNTs depends on the mode of substrate recognition. We have investigated the mechanism of substrate recognition of BoNT F by determining the crystal structures of its complex with two substrate-based inhibitors, VAMP 22-58/Gln58D-cysteine and 27-58/Gln58D-cysteine. The inhibitors bind to BoNT F in the canonical direction (as seen for BoNTs A and E substrates) but are positioned specifically via three major exosites away from the active site. The cysteine sulfur of the inhibitors interacts with the zinc and exists as sulfinic acid in the inhibitor VAMP 27-58/Gln58D-cysteine. Arg133 and Arg171, which form part of two separate exosites, are crucial for substrate binding and catalysis.

PubMed: 19543288
DOI: 10.1038/nsmb.1626

Experimental method

X-RAY DIFFRACTION (2.1 Å)