4b6f

Discovery of an allosteric mechanism for the regulation of HCV NS3 protein functionDiscovery of an allosteric mechanism for the regulation of HCV NS3 protein function

Structural highlights 4b6f is a 2 chain structure with sequence from Hepatitis c virus (isolate bk). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Related: 1a1q, 1bt7, 1c2p, 1csj, 1cu1, 1gx5, 1gx6, 1jxp, 1nhu, 1nhv, 1ns3, 1os5, 1quv, 2awz, 2ax0, 2ax1, 2brk, 2brl, 2i1r, 2jc0, 2jc1, 2wcx, 2who, 2xwy, 4a92, 4b6e, 8ohm Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Here we report a highly conserved new binding site located at the interface between the protease and helicase domains of the hepatitis C virus (HCV) NS3 protein. Using a chemical lead, identified by fragment screening and structure-guided design, we demonstrate that this site has a regulatory function on the protease activity via an allosteric mechanism. We propose that compounds binding at this allosteric site inhibit the function of the NS3 protein by stabilizing an inactive conformation and thus represent a new class of direct-acting antiviral agents. Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function.,Saalau-Bethell SM, Woodhead AJ, Chessari G, Carr MG, Coyle J, Graham B, Hiscock SD, Murray CW, Pathuri P, Rich SJ, Richardson CJ, Williams PA, Jhoti H Nat Chem Biol. 2012 Sep 30. doi: 10.1038/nchembio.1081. PMID:23023261 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 4b6f, resolution 2.89Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image