Elsevier

Biochimie

Volume 93, Issue 3, March 2011, Pages 513-518
Biochimie

Research paper
Crystal structure of Bn IV in complex with myristic acid: A Lys49 myotoxic phospholipase A2 from Bothrops neuwiedi venom

https://doi.org/10.1016/j.biochi.2010.11.003Get rights and content
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Abstract

The LYS49-PLA2s 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-PLA2 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-PLA2 was isolated from Bothrops neuwiedi snake venom in complex with myristic acid (CH3(CH2)12COOH) and its overall structure was refined at 2.2 Å resolution. The Bn IV crystals belong to monoclinic space group P21 and contain a dimer in the asymmetric unit. The unit cell parameters are a = 38.8, b = 70.4, c = 44.0 Å. 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.

Research highlights

► BN IV is a myotoxic phospholipase arrangement as a conventional dimmer. ► The relevant structural features for myotoxic activity are located in the C-terminal region. ► C-terminus is a probable heparin binding domain. ► Bn IV possible interact with muscle cell membranes mediated by heparin complexes.

Keywords

Phospholipase A2
Myristic acid
Myotoxin
Heparin

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