8dnd

Crystal structure of Bothrops pirajai Piratoxin-I (PrTX-I) and synthetic inhibitor Varespladib (LY315920)Crystal structure of Bothrops pirajai Piratoxin-I (PrTX-I) and synthetic inhibitor Varespladib (LY315920)

Structural highlights 8dnd is a 2 chain structure with sequence from Bothrops pirajai. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.018Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PA2H1_BOTPI Snake venom phospholipase A2 (PLA2) homolog that lacks enzymatic activity, but displays myotoxin and edema-inducing activities in vivo. In vitro neuromuscular activities have also been observed, but they are not found in vivo and can be explained by the destabilization of the muscle membrane by the toxin. The myotoxic activity is inhibited by rosmarinic acid (RA). Publication Abstract from PubMed Varespladib (LY315920) is a potent inhibitor of human group IIA phospholipase A(2) (PLA(2)) originally developed to control inflammatory cascades of diseases associated with high or dysregulated levels of endogenous PLA(2). Recently, varespladib was also found to inhibit snake venom PLA(2) and PLA(2)-like toxins. Herein, ex vivo neuromuscular blocking activity assays were used to test the inhibitory activity of varespladib. The binding affinity between varespladib and a PLA(2)-like toxin was quantified and compared with other potential inhibitors for this class of proteins. Crystallographic and bioinformatic studies showed that varespladib binds to PrTX-I and BthTX-I into their hydrophobic channels, similarly to other previously characterized PLA(2)-like myotoxins. However, a new finding is that an additional varespladib binds to the MDiS region, a particular site that is related to muscle cell disruption by these toxins. The present results further advance the characterization of the molecular interactions of varespladib with PLA(2)-like myotoxins and provide additional evidence for this compound as a promising inhibitor candidate for different PLA(2) and PLA(2)-like toxins. Structural basis of the myotoxic inhibition of the Bothrops pirajai PrTX-I by the synthetic varespladib.,Salvador GHM, Pinto EKR, Ortolani PL, Fortes-Dias CL, Cavalcante WLG, Soares AM, Lomonte B, Lewin MR, Fontes MRM Biochimie. 2023 Apr;207:1-10. doi: 10.1016/j.biochi.2022.11.006. Epub 2022 Nov , 17. PMID:36403756 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phospholipase A2 3D structures

spinqualitylabelsall models 8dnd, resolution 2.02Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image