3MLM

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

3MLM の概要

• エントリーDOI: 10.2210/pdb3mlm/pdb
• 分子名称: BN-IV Lys-49 Phospholipase A2, SULFATE ION, MYRISTIC ACID, ... (4 entities in total)
• 機能のキーワード: myotoxin, phospholipase-like protein, hydrolase
• 由来する生物種: Bothrops neuwiedi pauloensis (Neuwied's lancehead)
• 細胞内の位置: Secreted: Q9IAT9
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28203.01

構造登録者

Delatorre, P.,Rocha, B.A.M.,Cavada, B.S.,Toyama, M.H.,Toyama, D.,Gadelha, C.A.A. (登録日: 2010-04-17, 公開日: 2011-05-18, 最終更新日: 2024-10-16)

主引用文献

Delatorre, P.,Rocha, B.A.,Santi-Gadelha, T.,Gadelha, C.A.,Toyama, M.H.,Cavada, B.S.
Crystal structure of Bn IV in complex with myristic acid: a Lys49 myotoxic phospholipase A2 from Bothrops neuwiedi venom.
Biochimie, 93:513-518, 2011

PubMed 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.

PubMed: 21108987
DOI: 10.1016/j.biochi.2010.11.003

実験手法

X-RAY DIFFRACTION (2.21 Å)