| Structural highlights
Function
[PA2B1_BOTJR] Snake venom phospholipase A2 homolog that lacks enzymatic activity. In vivo, induces muscle necrosis, accompanied by polymorphonuclear cell infiltration, and edema in the mouse paw. Damages artificial and myoblast membranes by a calcium-independent mechanism. Has bactericidal activity.[1] [2] [3] [4] [5] [6] [7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Lys49 phospholipase A2 homologues are highly myotoxic and cause extensive tissue damage but do not display hydrolytic activity towards natural phospholipids. The binding of heparin, heparin derivatives and polyanionic compounds such as suramin result in partial inhibition (up to 60%) of the myotoxic effects due to a change in the overall charge of the interfacial surface. In vivo experiments demonstrate that polyethylene glycol inhibits more than 90% of the myotoxic effects without exhibiting secondary toxic effects. The crystal structure of bothropstoxin-I complexed with polyethylene glycol reveals that this inhibition is due to steric hindrance of the access to the PLA2-active site-like region. These two inhibitory pathways indicate the roles of the overall surface charge and free accessibility to the PLA2-active site-like region in the functioning of Lys49 phospholipases A2 homologues. Molecular dynamics simulations, small angle X-ray scattering and structural analysis indicate that the oligomeric states both in solution and in the crystalline states of Lys49 phospholipases A2 are principally mediated by hydrophobic contacts formed between the interfacial surfaces. These results provide the framework for the potential application of both clinically approved drugs for the treatment of Viperidae snakebites.
Interfacial surface charge and free accessibility to the PLA2-active site-like region are essential requirements for the activity of Lys49 PLA2 homologues.,Murakami MT, Vicoti MM, Abrego JR, Lourenzoni MR, Cintra AC, Arruda EZ, Tomaz MA, Melo PA, Arni RK Toxicon. 2007 Mar 1;49(3):378-87. Epub 2006 Nov 3. PMID:17157889[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Homsi-Brandeburgo MI, Queiroz LS, Santo-Neto H, Rodrigues-Simioni L, Giglio JR. Fractionation of Bothrops jararacussu snake venom: partial chemical characterization and biological activity of bothropstoxin. Toxicon. 1988;26(7):615-27. PMID:3176051
- ↑ Andriao-Escarso SH, Soares AM, Rodrigues VM, Angulo Y, Diaz C, Lomonte B, Gutierrez JM, Giglio JR. Myotoxic phospholipases A(2) in bothrops snake venoms: effect of chemical modifications on the enzymatic and pharmacological properties of bothropstoxins from Bothrops jararacussu. Biochimie. 2000 Aug;82(8):755-63. PMID:11018293
- ↑ Ward RJ, Chioato L, de Oliveira AH, Ruller R, Sa JM. Active-site mutagenesis of a Lys49-phospholipase A2: biological and membrane-disrupting activities in the absence of catalysis. Biochem J. 2002 Feb 15;362(Pt 1):89-96. PMID:11829743
- ↑ Chioato L, De Oliveira AH, Ruller R, Sa JM, Ward RJ. Distinct sites for myotoxic and membrane-damaging activities in the C-terminal region of a Lys49-phospholipase A2. Biochem J. 2002 Sep 15;366(Pt 3):971-6. PMID:12079495 doi:http://dx.doi.org/10.1042/BJ20020092
- ↑ Chioato L, Aragao EA, Lopes Ferreira T, Medeiros AI, Faccioli LH, Ward RJ. Mapping of the structural determinants of artificial and biological membrane damaging activities of a Lys49 phospholipase A2 by scanning alanine mutagenesis. Biochim Biophys Acta. 2007 May;1768(5):1247-57. Epub 2007 Feb 9. PMID:17346668 doi:http://dx.doi.org/10.1016/j.bbamem.2007.01.023
- ↑ Aragao EA, Chioato L, Ward RJ. Permeabilization of E. coli K12 inner and outer membranes by bothropstoxin-I, A LYS49 phospholipase A2 from Bothrops jararacussu. Toxicon. 2008 Mar 15;51(4):538-46. Epub 2007 Nov 17. PMID:18160090 doi:http://dx.doi.org/10.1016/j.toxicon.2007.11.004
- ↑ Murakami MT, Vicoti MM, Abrego JR, Lourenzoni MR, Cintra AC, Arruda EZ, Tomaz MA, Melo PA, Arni RK. Interfacial surface charge and free accessibility to the PLA2-active site-like region are essential requirements for the activity of Lys49 PLA2 homologues. Toxicon. 2007 Mar 1;49(3):378-87. Epub 2006 Nov 3. PMID:17157889 doi:10.1016/j.toxicon.2006.10.011
- ↑ Murakami MT, Vicoti MM, Abrego JR, Lourenzoni MR, Cintra AC, Arruda EZ, Tomaz MA, Melo PA, Arni RK. Interfacial surface charge and free accessibility to the PLA2-active site-like region are essential requirements for the activity of Lys49 PLA2 homologues. Toxicon. 2007 Mar 1;49(3):378-87. Epub 2006 Nov 3. PMID:17157889 doi:10.1016/j.toxicon.2006.10.011
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