3mlm | pdb_00003mlm
Crystal structure of Bn IV in complex with myristic acid: A Lys49 myotoxic phospholipase A2 from Bothrops neuwiedi venom
Structural highlights
Function[PA2H_BOTPA] Snake venom phospholipase A2 (PLA2) that lacks enzymatic activity. Is myotoxic. Displays bactericidal activity and promotes the blockage of the neuromuscular contraction of the chick biventer cervicis muscle. Also disrupts artificial membranes, and provokes tissue damages characterized by edema, necrosis and inflammation. May act as pro-inflammatory mediators, inducing metalloproteinase and cytokine production from the inflammatory and satellite cells.[1] [2] [3] Publication Abstract from PubMedThe LYS49-PLAs myotoxins have attracted attention as models for the induction of myonecrosis by a catalytically independent mechanism of action. Structural studies and biological activities have demonstrated that the myotoxic activity of LYS49-PLA is independent of the catalytic activity site. The myotoxic effect is conventionally thought to be to due to the C-terminal region 111-121, which plays an effective role in membrane damage. In the present study, Bn IV LYS49-PLA was isolated from Bothrops neuwiedi snake venom in complex with myristic acid (CH(CH)COOH) and its overall structure was refined at 2.2 A resolution. The Bn IV crystals belong to monoclinic space group P2 and contain a dimer in the asymmetric unit. The unit cell parameters are a = 38.8, b = 70.4, c = 44.0 A. The biological assembly is a "conventional dimer" and the results confirm that dimer formation is not relevant to the myotoxic activity. Electron density map analysis of the Bn IV structure shows clearly the presence of myristic acid in catalytic site. The relevant structural features for myotoxic activity are located in the C-terminal region and the Bn IV C-terminal residues NKKYRY are a probable heparin binding domain. These findings indicate that the mechanism of interaction between Bn IV and muscle cell membranes is through some kind of cell signal transduction mediated by heparin complexes. Crystal structure of Bn IV in complex with myristic acid: a Lys49 myotoxic phospholipase A from Bothrops neuwiedi venom.,Delatorre P, Rocha BA, Santi-Gadelha T, Gadelha CA, Toyama MH, Cavada BS Biochimie. 2011 Mar;93(3):513-8. Epub 2010 Nov 22. PMID:21108987[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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