3vbz

Crystal structure of Taipoxin beta subunit isoform 2Crystal structure of Taipoxin beta subunit isoform 2

Structural highlights 3vbz is a 2 chain structure with sequence from Oxyuranus scutellatus scutellatus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.76Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PA2HC_OXYSC Heterotrimer: Snake venom phospholipase A2 (PLA2) heterotrimer that acts as a potent presynaptic neurotoxin by blocking synaptic transmission and synaptic vesicle recycling. May act by binding in a calcium-dependent fashion to neurotonal pentraxin-1 (NPTX1) and neurotonal pentraxin-2 (NPTX2), but not to neuronal pentraxin receptor (NPTXR). Also binds to taipoxin-associated calcium binding protein 49 (RCN2), a protein localized in the lumen of endoplasmic reticulum. Monomer (beta chain): Snake venom phospholipase A2 homolog that is neither toxic nor enzymatically active. Does not bind calcium. Publication Abstract from PubMed Snake pre-synaptic neurotoxins endowed with phospholipase A(2) activity are potent inducers of paralysis through the specific disruption of the neuromuscular junction pre-synaptic membrane and represent a valuable tool for investigating neuronal degeneration and recovery. They have different structural complexity and a wide range of lethal potency and enzymatic activity, although they share a similar mechanism of action. Although no correlation has been reported between neurotoxicity and enzymatic activity, toxicity increases with structural complexity and phospholipase A(2) oligomers show 10-fold lower LD(50) values compared to their monomeric counterparts. To date, no structural study has been performed on multimeric SPANs with the aim of shedding light on the correlation between structural complexity and neurotoxicity. In the present study, we investigated the structure of taipoxin, a trimeric phospholipase A(2) neurotoxin, as well as that of its subunits, by X-ray crystallography and small angle X-ray scattering analysis. We present the high-resolution structure of two isoforms of the taipoxin beta subunit, which show no neurotoxic activity but enhance the activity of the other subunits in the complex. One isoform shows no structural change that could justify the lack of activity. The other displays three point mutations in critical positions for the catalytic activity. Moreover, we designed a model for the quaternary structure of taipoxin under physiological conditions, in which the three subunits are organized into a flat holotoxin with the substrate binding sockets exposed on the same side of the complex, which suggests a role for this interface in the toxin-membrane interaction. Database The coordinates and structure factors have been deposited in the RCSB Protein Data Bank (http://www.rcsb.org) under accession numbers 3VBZ and 3VCO, corresponding to beta isoforms 1 and 2 respectively Structure digital abstract * taipoxin beta isoform 2 and taipoxin beta isoform 2 bind by x-ray crystallography (View interaction). Structural analysis of trimeric phospholipase A(2) neurotoxin from the Australian taipan snake venom.,Cendron L, Micetic I, Polverino de Laureto P, Paoli M FEBS J. 2012 Jul 6. doi: 10.1111/j.1742-4658.2012.08691.x. PMID:22776098 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phospholipase A2 homolog

spinqualitylabelsall models 3vbz, resolution 1.76Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image