6CE2

Crystal structure of Myotoxin I (MjTX-I) from Bothrops moojeni complexed to inhibitor suramin

6CE2 の概要

• エントリーDOI: 10.2210/pdb6ce2/pdb
• 関連するPDBエントリー: 3T0R
• 分子名称: Basic phospholipase A2 homolog 1, 2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL, 8,8'-[CARBONYLBIS[IMINO-3,1-PHENYLENECARBONYLIMINO(4-METHYL-3,1-PHENYLENE)CARBONYLIMINO]]BIS-1,3,5-NAPHTHALENETRISULFON IC ACID, ... (4 entities in total)
• 機能のキーワード: myotoxin i, mjtx-i, pla2-like, suramin, 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: 29588.44

構造登録者

Salvador, G.H.M.,Fontes, M.R.M. (登録日: 2018-02-10, 公開日: 2018-07-25, 最終更新日: 2024-10-23)

主引用文献

Salvador, G.H.M.,Dreyer, T.R.,Gomes, A.A.S.,Cavalcante, W.L.G.,Dos Santos, J.I.,Gandin, C.A.,de Oliveira Neto, M.,Gallacci, M.,Fontes, M.R.M.
Structural and functional characterization of suramin-bound MjTX-I from Bothrops moojeni suggests a particular myotoxic mechanism.
Sci Rep, 8:10317-10317, 2018

PubMed Abstract: Local myonecrosis is the main event resulting from snakebite envenomation by the Bothrops genus and, frequently, it is not efficiently neutralized by antivenom administration. Proteases, phospholipases A (PLA) and PLA-like toxins are found in venom related to muscle damage. Functional sites responsible for PLA-like toxins activity have been proposed recently; they consist of a membrane docking-site and a membrane rupture-site. Herein, a combination of functional, biophysical and crystallographic techniques was used to characterize the interaction between suramin and MjTX-I (a PLA-like toxin from Bothrops moojeni venom). Functional in vitro neuromuscular assays were performed to study the biological effects of the protein-ligand interaction, demonstrating that suramin neutralizes the myotoxic effect of MjTX-I. Calorimetric assays showed two different binding events: (i) inhibitor-protein interactions and (ii) toxin oligomerization processes. These hypotheses were also corroborated with dynamic light and small angle X-ray scattering assays. The crystal structure of the MjTX-I/suramin showed a totally different interaction mode compared to other PLA-like/suramin complexes. Thus, we suggested a novel myotoxic mechanism for MjTX-I that may be inhibited by suramin. These results can further contribute to the search for inhibitors that will efficiently counteract local myonecrosis in order to be used as an adjuvant of conventional serum therapy.

PubMed: 29985425
DOI: 10.1038/s41598-018-28584-7

実験手法

X-RAY DIFFRACTION (2.15 Å)