2xhl

STRUCTURE OF A FUNCTIONAL DERIVATIVE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN TYPE B

spinqualitylabelsall models 2xhl, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xhl is a 2 chain structure with sequence from Clostridium botulinum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ZN Related: 1s0d, 1epw, 1g9b, 1f82, 2etf, 1i1e, 1s0f, 1g9a, 1g9c, 1s0b, 1s0g, 1s0c, 1g9d, 1z0h, 1f31, 1s0e Activity: Bontoxilysin, with EC number 3.4.24.69 Resources: FirstGlance, OCA, RCSB, PDBsum 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. Publication Abstract from PubMed Botulinum neurotoxins (BoNTs) cause flaccid paralysis by inhibiting neurotransmission at cholinergic nerve terminals. BoNTs consist of three essential domains for toxicity: the cell binding domain (Hc), the translocation domain (Hn) and the catalytic domain (LC). A functional derivative (LHn) of the parent neurotoxin B composed of Hn and LC domains was recombinantly produced and characterised. LHn/B crystallographic structure at 2.8A resolution is reported. The catalytic activity of LHn/B towards recombinant human VAMP was analysed by substrate cleavage assay and showed a higher specificity for VAMP-1, -2 compared to VAMP-3. LHn/B also showed measurable activity in living spinal cord neurons. Despite lacking the Hc (cell-targeting) domain, LHn/B retained the capacity to internalize and cleave intracellular VAMP-1 and -2 when added to the cells at high concentration. These activities of the LHn/B fragment demonstrate the utility of engineered botulinum neurotoxin fragments as analytical tools to study the mechanisms of action of BoNT neurotoxins and of SNARE proteins. Structure and activity of a functional derivative of Clostridium botulinum neurotoxin B.,Masuyer G, Beard M, Cadd VA, Chaddock JA, Acharya KR J Struct Biol. 2010 Nov 13. PMID:21078393 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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