3m5o

Crystal structure of HCV NS3/4A protease in complex with N-terminal product 5A5B

spinqualitylabelsall models 3m5o, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3m5o is a 4 chain structure with sequence from Hepatitis C virus genotype 1a. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.6Å Ligands: ACE, SO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B3TKQ3_9HEPC Publication Abstract from PubMed Hepatitis C virus infects an estimated 180 million people worldwide, prompting enormous efforts to develop inhibitors targeting the essential NS3/4A protease. Resistance against the most promising protease inhibitors, telaprevir, boceprevir, and ITMN-191, has emerged in clinical trials. In this study, crystal structures of the NS3/4A protease domain reveal that viral substrates bind to the protease active site in a conserved manner defining a consensus volume, or substrate envelope. Mutations that confer the most severe resistance in the clinic occur where the inhibitors protrude from the substrate envelope, as these changes selectively weaken inhibitor binding without compromising the binding of substrates. These findings suggest a general model for predicting the susceptibility of protease inhibitors to resistance: drugs designed to fit within the substrate envelope will be less susceptible to resistance, as mutations affecting inhibitor binding would simultaneously interfere with the recognition of viral substrates. Drug resistance against HCV NS3/4A inhibitors is defined by the balance of substrate recognition versus inhibitor binding.,Romano KP, Ali A, Royer WE, Schiffer CA Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):20986-91. Epub 2010 Nov 17. PMID:21084633 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Virus protease 3D structures

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