6CE2

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

Summary for 6CE2

• Entry DOI: 10.2210/pdb6ce2/pdb
• Related: 3T0R
• Descriptor: 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)
• Functional Keywords: myotoxin i, mjtx-i, pla2-like, suramin, toxin
• Biological source: Bothrops moojeni (Lance-headed viper)
• Total number of polymer chains: 2
• Total formula weight: 29588.44

Authors

Salvador, G.H.M.,Fontes, M.R.M. (deposition date: 2018-02-10, release date: 2018-07-25, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.15 Å)