| Structural highlights
3cxi is a 2 chain structure with sequence from Bothrops jararacussu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| Related: | 1clp, 1pa0, 1pc9, 2q2j, 3cyl, 1y4l |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
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
Phospholipases A(2) (PLA(2)s) are membrane-associated enzymes that hydrolyze phospholipids at the sn-2 position, releasing lysophospholipids and free fatty acids. Phospholipase A(2) homologues (Lys49-PLA(2)s) are highly myotoxic and cause extensive tissue damage despite not showing measurable catalytic activity. They are found in different snake venoms and represent one third of bothropic venom composition. The importance of these toxins during envenomation is related to the pronounced local myotoxic effect they induce since this effect is not neutralized by serum therapy. We present herein three structures of Lys49-PLA(2)s from Bothrops genus snake venom crystallized under the same conditions, two of which were grown in the presence of alpha-tocopherol (vitamin E). Comparative structural analysis of these and other Lys49-PLA(2)s showed two different patterns of oligomeric conformation that are related to the presence or absence of ligands in the hydrophobic channel. This work also confirms the biological dimer indicated by recent studies in which both C-termini are in the dimeric interface. In this configuration, we propose that the myotoxic site of these toxins is composed by the Lys 20, Lys115 and Arg118 residues. For the first time, a residue from the short-helix (Lys20) is suggested as a member of this site and the importance of Tyr119 residue to myotoxicity of bothropic Lys49-PLA(2)s is also discussed. These results support a complete hypothesis for these PLA(2)s myotoxic activity consistent with all findings on bothropic Lys49-PLA(2)s studied up to this moment, including crystallographic, bioinformatics, biochemical and biophysical data.
Comparative structural studies on Lys49-phospholipases A(2) from Bothrops genus reveal their myotoxic site.,dos Santos JI, Soares AM, Fontes MR J Struct Biol. 2009 Aug;167(2):106-16. Epub 2009 May 3. PMID:19401234[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ dos Santos JI, Soares AM, Fontes MR. Comparative structural studies on Lys49-phospholipases A(2) from Bothrops genus reveal their myotoxic site. J Struct Biol. 2009 Aug;167(2):106-16. Epub 2009 May 3. PMID:19401234 doi:10.1016/j.jsb.2009.04.003
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