3vbz

Structural highlights

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]}

See Also

• Phospholipase A2 homolog

References

1. ↑ 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
2. ↑ 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
3. ↑ 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
4. ↑ 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
5. ↑ 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
6. ↑ 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
7. ↑ 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