6ce2 | pdb_00006ce2
Crystal structure of Myotoxin I (MjTX-I) from Bothrops moojeni complexed to inhibitor suramin
Structural highlights
FunctionPA2H1_BOTMO Snake venom phospholipase A2 homolog that displays local myotoxin and edema-inducing activities and is lethal by intraperitoneal injection.[1] Publication Abstract from PubMedLocal 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 A2 (PLA2) and PLA2-like toxins are found in venom related to muscle damage. Functional sites responsible for PLA2-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 PLA2-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 PLA2-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. Structural and functional characterization of suramin-bound MjTX-I from Bothrops moojeni suggests a particular myotoxic mechanism.,Salvador GHM, Dreyer TR, Gomes AAS, Cavalcante WLG, Dos Santos JI, Gandin CA, de Oliveira Neto M, Gallacci M, Fontes MRM Sci Rep. 2018 Jul 9;8(1):10317. doi: 10.1038/s41598-018-28584-7. PMID:29985425[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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