1g9a

CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN B COMPLEXED WITH AN INHIBITOR (EXPERIMENT 3)

spinqualitylabelsall models 1g9a, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1g9a is a 1 chain structure with sequence from Clostridium botulinum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: BAB, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BXB_CLOBO Botulinum toxin acts by inhibiting neurotransmitter release. It binds to peripheral neuronal synapses, is internalized and moves by retrograde transport up the axon into the spinal cord where it can move between postsynaptic and presynaptic neurons. It inhibits neurotransmitter release by acting as a zinc endopeptidase that cleaves the '76-Gln-|-Phe-77' bond of synaptobrevin-2. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. A novel mechanism for Clostridium botulinum neurotoxin inhibition.,Eswaramoorthy S, Kumaran D, Swaminathan S Biochemistry. 2002 Aug 6;41(31):9795-802. PMID:12146945 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Botulinum neurotoxin 3D structures

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