6B83

Crystal structure of Myotoxin II from Bothrops moojeni complexed to Caproic acid

6B83 の概要

• エントリーDOI: 10.2210/pdb6b83/pdb
• 関連するPDBエントリー: 4KF3 4YV5
• 分子名称: Basic phospholipase A2 homolog 2, HEXANOIC ACID, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: myotoxin ii, bothrops moojeni, phospholipase a2-like, toxin
• 由来する生物種: Bothrops moojeni (Lance-headed viper)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28460.83

構造登録者

Salvador, G.H.M.,dos Santos, J.I.,Fontes, M.R.M. (登録日: 2017-10-05, 公開日: 2018-10-03, 最終更新日: 2024-10-30)

主引用文献

Salvador, G.H.M.,Dos Santos, J.I.,Borges, R.J.,Fontes, M.R.M.
Structural evidence for a fatty acid-independent myotoxic mechanism for a phospholipase A2-like toxin.
Biochim Biophys Acta Proteins Proteom, 1866:473-481, 2018

PubMed Abstract: The myotoxic mechanism for PLA-like toxins has been proposed recently to be initiated by an allosteric change induced by a fatty acid binding to the protein, leading to the alignment of the membrane docking site (MDoS) and membrane disrupting site (MDiS). Previous structural studies performed by us demonstrated that MjTX-II, a PLA-like toxin isolated from Bothrops moojeni, presents a different mode of ligand-interaction caused by natural amino acid substitutions and an insertion. Herein, we present four crystal structures of MjTX-II, in its apo state and complexed with fatty acids of different lengths. Analyses of these structures revealed slightly different oligomeric conformations but with both MDoSs in an arrangement that resembles an active-state PLA-like structure. To explore the structural transitions between apo protein and fatty-acid complexes, we performed Normal Mode Molecular Dynamics simulations, revealing that oligomeric conformations of MjTX-II/fatty acid complexes may be reached in solution by the apo structure. Similar simulations with typical PLA-like structures demonstrated that this transition is not possible without the presence of fatty acids. Thus, we hypothesize that MjTX-II does not require fatty acids to be active, although these ligands may eventually help in its stabilization by the formation of hydrogen bonds. Therefore, these results complement previous findings for MjTX-II and help us understand its particular ligand-binding properties and, more importantly, its particular mechanism of action, with a possible impact on the design of structure-based inhibitors for PLA-like toxins in general.

PubMed: 29287778
DOI: 10.1016/j.bbapap.2017.12.008

実験手法

X-RAY DIFFRACTION (1.7 Å)