2wuc | pdb_00002wuc

Crystal structure of HGFA in complex with the allosteric non- inhibitory antibody Fab40.deltaTrp and Ac-KQLR-chloromethylketone

spinqualitylabelsall models 2wuc, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2wuc is a 5 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NAG NonStd Res: 0QE, ACE, AR7 Related: 1ybw, 1yc0, 2wub Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [HGFA_HUMAN] Activates hepatocyte growth factor (HGF) by converting it from a single chain to a heterodimeric form. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Recent structural studies have outlined the mechanism of protease inhibition by active site-directed antibodies. However, the molecular basis of allosteric inhibition by antibodies has been elusive. Here we report the 2.35 A resolution structure of the trypsin-like serine protease hepatocyte growth factor activator (HGFA) in complex with the allosteric antibody Ab40, a potent inhibitor of HGFA catalytic activity. The antibody binds at the periphery of the substrate binding cleft and imposes a conformational change on the entire 99-loop (chymotrypsinogen numbering). The altered conformation of the 99-loop is incompatible with substrate binding due to the partial collapse of subsite S2 and the reorganization of subsite S4. Remarkably, a single residue deletion of Ab40 abolished inhibition of HGFA activity, commensurate with the reversal of the 99-loop conformation to its "competent" state. The results define an "allosteric switch" mechanism as the basis of protease inhibition by an allosteric antibody. Unraveling the allosteric mechanism of serine protease inhibition by an antibody.,Ganesan R, Eigenbrot C, Wu Y, Liang WC, Shia S, Lipari MT, Kirchhofer D Structure. 2009 Dec 9;17(12):1614-24. PMID:20004165 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody Hepatocyte growth factor activator

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