6ce2 | pdb_00006ce2

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

spinqualitylabelsall models 6ce2, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ce2 is a 2 chain structure with sequence from Bothrops moojeni. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.15Å Ligands: PE4, SVR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PA2H1_BOTMO Snake venom phospholipase A2 homolog that displays local myotoxin and edema-inducing activities and is lethal by intraperitoneal injection. Publication Abstract from PubMed 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 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phospholipase A2 homolog

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