9clp | pdb_00009clp

Structure of ecarin from the venom of Kenyan saw-scaled viper in complex with the Fab of neutralizing antibody H11

spinqualitylabelsall models 9clp, resolution 3.43Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9clp is a 4 chain structure with sequence from Echis carinatus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.43Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function VM3E_ECHCA Snake venom zinc metalloproteinase that catalyzes the conversion of prothrombin (F2) to alpha-thrombin through formation of a thrombin intermediate. Has a low Km for prothrombin and a high kcat. Cleaves the 320-Arg-Ile-321 bond in prothrombin and produces meizothrombin which is ultimately converted to alpha-thrombin by autolysis. Publication Abstract from PubMed Snake venoms are cocktails of biologically active molecules that have evolved to immobilize prey, but can also induce a severe pathology in humans that are bitten. While animal-derived polyclonal antivenoms are the primary treatment for snakebites, they often have limitations in efficacy and can cause severe adverse side effects. Building on recent efforts to develop improved antivenoms, notably through monoclonal antibodies, requires a comprehensive understanding of venom toxins. Among these toxins, snake venom metalloproteinases (SVMPs) play a pivotal role, particularly in viper envenomation, causing tissue damage, hemorrhage and coagulation disruption. One of the current challenges in the development of neutralizing monoclonal antibodies against SVMPs is the large size of the protein and the lack of existing knowledge of neutralizing epitopes. Here, we screened a synthetic human antibody library to isolate monoclonal antibodies against an SVMP from saw-scaled viper (genus Echis) venom. Upon characterization, several antibodies were identified that effectively blocked SVMP-mediated prothrombin activation. Cryo-electron microscopy revealed the structural basis of antibody-mediated neutralization, pinpointing the non-catalytic cysteine-rich domain of SVMPs as a crucial target. These findings emphasize the importance of understanding the molecular mechanisms of SVMPs to counter their toxic effects, thus advancing the development of more effective antivenoms. Importance of the Cysteine-Rich Domain of Snake Venom Prothrombin Activators: Insights Gained from Synthetic Neutralizing Antibodies.,Misson Mindrebo LE, Mindrebo JT, Tran Q, Wilkinson MC, Smith JM, Verma M, Casewell NR, Lander GC, Jardine JG Toxins (Basel). 2024 Aug 15;16(8):361. doi: 10.3390/toxins16080361. PMID:39195771 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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