3rlg

Structural highlights

Function

A1HA_LOXIN Catalyzes the hydrolysis of sphingomyelin, lysophosphatidylcholine, and lyso-platelet activating factor but not that of phosphatidylcholine. Shows a high enzymatic activity. Induces dermonecrosis, blood vessel permeability and platelet aggregation (PubMed:9790962). Is directly toxic to kidney (PubMed:16005484) and liver (PubMed:18765244). Also induces hemolysis in a complement-dependent manner (PubMed:9790962) as well as in a complement-independent manner. The hemolysis provoked in a complement-independent manner is composed of several steps. The toxin binds to erythrocyte membranes, hydrolyzes membrane phospholipids (sphingomyelin and lysophosphatidylcholine) thus generating metabolism products that cause hemolysis, probably by provoking an increase of calcium inside cells. The calcium influx is due to the opening of L-type calcium channels, since L-type calcium channel blockers inhibit calcium influx (PubMed:21590705).^{[1] [2] [3] [4] [5] [6]}

See Also

• Phospholipase D 3D structures
• Sphingomyelinase

References

1. ↑ Chaim OM, Sade YB, da Silveira RB, Toma L, Kalapothakis E, Chavez-Olortegui C, Mangili OC, Gremski W, von Dietrich CP, Nader HB, Sanches Veiga S. Brown spider dermonecrotic toxin directly induces nephrotoxicity. Toxicol Appl Pharmacol. 2006 Feb 15;211(1):64-77. Epub 2005 Jul 11. PMID:16005484 doi:http://dx.doi.org/S0041-008X(05)00361-3
2. ↑ Kusma J, Chaim OM, Wille AC, Ferrer VP, Sade YB, Donatti L, Gremski W, Mangili OC, Veiga SS. Nephrotoxicity caused by brown spider venom phospholipase-D (dermonecrotic toxin) depends on catalytic activity. Biochimie. 2008 Nov-Dec;90(11-12):1722-36. doi: 10.1016/j.biochi.2008.07.011., Epub 2008 Aug 9. PMID:18760322 doi:http://dx.doi.org/10.1016/j.biochi.2008.07.011
3. ↑ de Oliveira Christoff A, de Oliveira A, Chaim OM, Lugarini D, Bastos Pereira AL, Paludo KS, Queiroz Telles JE, Bracht A, Veiga SS, Acco A. Effects of the venom and the dermonecrotic toxin LiRecDT1 of Loxosceles intermedia in the rat liver. Toxicon. 2008 Nov;52(6):695-704. Epub 2008 Aug 13. PMID:18765244 doi:http://dx.doi.org/S0041-0101(08)00457-1
4. ↑ Chaves-Moreira D, Chaim OM, Sade YB, Paludo KS, Gremski LH, Donatti L, de Moura J, Mangili OC, Gremski W, da Silveira RB, Senff-Ribeiro A, Veiga SS. Identification of a direct hemolytic effect dependent on the catalytic activity induced by phospholipase-D (dermonecrotic toxin) from brown spider venom. J Cell Biochem. 2009 Jul 1;107(4):655-66. doi: 10.1002/jcb.22148. PMID:19455508 doi:http://dx.doi.org/10.1002/jcb.22148
5. ↑ Chaves-Moreira D, Souza FN, Fogaca RT, Mangili OC, Gremski W, Senff-Ribeiro A, Chaim OM, Veiga SS. The relationship between calcium and the metabolism of plasma membrane phospholipids in hemolysis induced by brown spider venom phospholipase-D toxin. J Cell Biochem. 2011 Sep;112(9):2529-40. doi: 10.1002/jcb.23177. PMID:21590705 doi:http://dx.doi.org/10.1002/jcb.23177
6. ↑ Tambourgi DV, Magnoli FC, van den Berg CW, Morgan BP, de Araujo PS, Alves EW, Da Silva WD. Sphingomyelinases in the venom of the spider Loxosceles intermedia are responsible for both dermonecrosis and complement-dependent hemolysis. Biochem Biophys Res Commun. 1998 Oct 9;251(1):366-73. PMID:9790962 doi:http://dx.doi.org/S0006-291X(98)99474-8