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3vc0

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Revision as of 07:35, 11 August 2016

Crystal structure of Taipoxin beta subunit isoform 1

Structural highlights

3vc0 is a 1 chain structure with sequence from Australian taipan. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	3vbz
Activity:	Phospholipase A(2), with EC number 3.1.1.4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PA22_OXYSC] Snake venom phospholipase A2 (PLA2) that shows high presynaptic neurotoxicity in vertebrata that is independent of catalytic activity (PubMed:2544597, PubMed:10548416 and PubMed:16669624), as well as local myotoxicity when intramuscularly injected into mice (PubMed:16669624). Blocks acetylcholine release in Aplysia neurons (PubMed:8583413), and potentiates proinflammatory cellular signaling (PubMed:12782627). Potentiates glutamate excitoxicity when coinjected into brain of rats (PubMed:10548416). May act by binding in a calcium-dependent fashion and with high affinity to a neuronal-type (N-type) PLA2 receptor, and with very high affinity to a muscle-type (M-type) PLA2 receptor. In vitro, shows a high-specific activity on E.coli membranes and is more efficient on the anionic phospholipid POPG than on the anionic phospholipid POPS or the zwitterionic phospholipid POPC. Exerts catalytically-independent anti-HIV (IC(50) is 35 nM) activity and catalytically-dependent antimalarial activity (IC(50) is 3.1 nM when tested on P.falciparum grown in serum that contains lipoproteins). PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

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^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kolko M, Bruhn T, Christensen T, Lazdunski M, Lambeau G, Bazan NG, Diemer NH. Secretory phospholipase A2 potentiates glutamate-induced rat striatal neuronal cell death in vivo. Neurosci Lett. 1999 Oct 29;274(3):167-70. PMID:10548416
↑ Beck S, Lambeau G, Scholz-Pedretti K, Gelb MH, Janssen MJ, Edwards SH, Wilton DC, Pfeilschifter J, Kaszkin M. Potentiation of tumor necrosis factor alpha-induced secreted phospholipase A2 (sPLA2)-IIA expression in mesangial cells by an autocrine loop involving sPLA2 and peroxisome proliferator-activated receptor alpha activation. J Biol Chem. 2003 Aug 8;278(32):29799-812. Epub 2003 Jun 2. PMID:12782627 doi:http://dx.doi.org/10.1074/jbc.M211763200
↑ Rouault M, Rash LD, Escoubas P, Boilard E, Bollinger J, Lomonte B, Maurin T, Guillaume C, Canaan S, Deregnaucourt C, Schrevel J, Doglio A, Gutierrez JM, Lazdunski M, Gelb MH, Lambeau G. Neurotoxicity and other pharmacological activities of the snake venom phospholipase A2 OS2: the N-terminal region is more important than enzymatic activity. Biochemistry. 2006 May 9;45(18):5800-16. PMID:16669624 doi:http://dx.doi.org/10.1021/bi060217r
↑ Lambeau G, Schmid-Alliana A, Lazdunski M, Barhanin J. Identification and purification of a very high affinity binding protein for toxic phospholipases A2 in skeletal muscle. J Biol Chem. 1990 Jun 5;265(16):9526-32. PMID:2160984
↑ Lambeau G, Barhanin J, Schweitz H, Qar J, Lazdunski M. Identification and properties of very high affinity brain membrane-binding sites for a neurotoxic phospholipase from the taipan venom. J Biol Chem. 1989 Jul 5;264(19):11503-10. PMID:2544597
↑ Fossier P, Lambeau G, Lazdunski M, Baux G. Inhibition of ACh release at an Aplysia synapse by neurotoxic phospholipases A2: specific receptors and mechanisms of action. J Physiol. 1995 Nov 15;489 ( Pt 1):29-40. PMID:8583413
↑ Cendron L, Micetic I, Polverino de Laureto P, Paoli M. Structural analysis of trimeric phospholipase A(2) neurotoxin from the Australian taipan snake venom. FEBS J. 2012 Jul 6. doi: 10.1111/j.1742-4658.2012.08691.x. PMID:22776098 doi:10.1111/j.1742-4658.2012.08691.x

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3vc0"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Taipoxin beta subunit isoform 1==
 <StructureSection load='3vc0' size='340' side='right' caption='[[3vc0]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3vc0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Oxyuranus_scutellatus_scutellatus Oxyuranus scutellatus scutellatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VC0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VC0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3vc0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Australian_taipan Australian taipan]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VC0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VC0 FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3vbz|3vbz]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.4 3.1.1.4] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vc0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vc0 RCSB], [http://www.ebi.ac.uk/pdbsum/3vc0 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vc0 OCA], [http://pdbe.org/3vc0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vc0 RCSB], [http://www.ebi.ac.uk/pdbsum/3vc0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vc0 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/PA22_OXYSC PA22_OXYSC]] Snake venom phospholipase A2 (PLA2) that shows high presynaptic neurotoxicity in vertebrata that is independent of catalytic activity (PubMed:2544597, PubMed:10548416 and PubMed:16669624), as well as local myotoxicity when intramuscularly injected into mice (PubMed:16669624). Blocks acetylcholine release in Aplysia neurons (PubMed:8583413), and potentiates proinflammatory cellular signaling (PubMed:12782627). Potentiates glutamate excitoxicity when coinjected into brain of rats (PubMed:10548416). May act by binding in a calcium-dependent fashion and with high affinity to a neuronal-type (N-type) PLA2 receptor, and with very high affinity to a muscle-type (M-type) PLA2 receptor. In vitro, shows a high-specific activity on E.coli membranes and is more efficient on the anionic phospholipid POPG than on the anionic phospholipid POPS or the zwitterionic phospholipid POPC. Exerts catalytically-independent anti-HIV (IC(50) is 35 nM) activity and catalytically-dependent antimalarial activity (IC(50) is 3.1 nM when tested on P.falciparum grown in serum that contains lipoproteins). PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.<ref>PMID:10548416</ref> <ref>PMID:12782627</ref> <ref>PMID:16669624</ref> <ref>PMID:2160984</ref> <ref>PMID:2544597</ref> <ref>PMID:8583413</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 15: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3vc0" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Oxyuranus scutellatus scutellatus]]
+[[Category: Australian taipan]]
 [[Category: Beltramini, M]]
 [[Category: Cendron, L]]

3vc0

From Proteopedia

Revision as of 07:35, 11 August 2016

Crystal structure of Taipoxin beta subunit isoform 1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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