1g9c
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CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN B COMPLEXED WITH AN INHIBITOR (EXPERIMENT 4)
OverviewOverview
Clostridium botulinum neurotoxins are zinc endopeptidase proteins, responsible for cleaving specific peptide bonds of proteins of, neuroexocytosis apparatus. The ability of drugs to interfere with toxin's, catalytic activity is being evaluated with zinc chelators and, metalloprotease inhibitors. It is important to develop effective, pharmacological treatment for the intact holotoxin before the catalytic, domain separates and enters the cytosol. We present here evidence for a, novel mechanism of an inhibitor binding to the holotoxin and for the, chelation of zinc from our structural studies on Clostridium botulinum, neurotoxin type B in complex with a potential metalloprotease inhibitor, bis(5-amidino-2-benzimidazolyl)methane, and provide snapshots of the, reaction as it progresses. The binding and inhibition mechanism of this, inhibitor to the neurotoxin seems to be unique for intact botulinum, neurotoxins. The environment of the active site rearranges in the presence, of the inhibitor, and the zinc ion is gradually removed from the active, site and transported to a different site in the protein, probably causing, loss of catalytic activity.
About this StructureAbout this Structure
1G9C is a Single protein structure of sequence from Clostridium botulinum with ZN and BAB as ligands. Active as Bontoxilysin, with EC number 3.4.24.69 Full crystallographic information is available from OCA.
ReferenceReference
A novel mechanism for Clostridium botulinum neurotoxin inhibition., Eswaramoorthy S, Kumaran D, Swaminathan S, Biochemistry. 2002 Aug 6;41(31):9795-802. PMID:12146945
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