2g7n

Structure of the Light Chain of Botulinum Neurotoxin Serotype A Bound to small Molecule Inhibitors

spinqualitylabelsall models 2g7n, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2g7n 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 1.9Å Ligands: AG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BXA2_CLOBJ Botulinum toxin causes flaccid paralysis by inhibiting neurotransmitter (acetylcholine) release from the presynaptic membranes of nerve terminals of eukaryotic host skeletal and autonomic nervous system, with frequent heart or respiratory failure. Precursor of botulinum neurotoxin A2 which has 2 coreceptors; complex polysialylated gangliosides found on neural tissue and specific membrane-anchored proteins found in synaptic vesicles. Receptor proteins are exposed on host presynaptic cell membrane during neurotransmitter release, when the toxin heavy chain (HC) binds to them. Upon synaptic vesicle recycling the toxin is taken up via the endocytic pathway. When the pH of the toxin-containing endosome drops a structural rearrangement occurs so that the N-terminus of the HC forms pores that allows the light chain (LC) to translocate into the cytosol. Once in the cytosol the disulfide bond linking the 2 subunits is reduced and LC cleaves its target protein on synaptic vesicles, preventing their fusion with the cytoplasmic membrane and thus neurotransmitter release (By similarity).[UniProtKB:P0DPI0] Has proteolytic activity. After translocation into the eukaryotic host cytosol, LC hydrolyzes the 197-Gln-|-Arg-198 bond in SNAP25, blocking neurotransmitter release (PubMed:16846233). Responsible for host epithelial cell transcytosis, host nerve cell targeting and translocation of light chain (LC) into host cytosol. Composed of 3 subdomains; the translocation domain (TD), and N-terminus and C-terminus of the receptor-binding domain (RBD). The RBD is responsible for the adherence of the toxin to the cell surface. It simultaneously recognizes 2 coreceptors; polysialated gangliosides and the receptor protein SV2 in close proximity on host synaptic vesicles (PubMed:28252640, PubMed:29649119). The N-terminus of the TD wraps an extended belt around the perimeter of the LC, protecting Zn(2+) in the active site; it may also prevent premature LC dissociation from the translocation channel and to protect toxin prior to translocation (By similarity). The TD inserts into synaptic vesicle membrane to allow translocation into the host cytosol (By similarity).[UniProtKB:P0DPI0] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. See Also Botulinum neurotoxin 3D structures

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