4i31 | pdb_00004i31

Crystal structure of HCV NS3/NS4A protease complexed with compound 4

spinqualitylabelsall models 4i31, resolution 1.93Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4i31 is a 4 chain structure with sequence from Hepatitis c virus (isolate japanese). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 1BV, NA Gene: POLG_HCVJA (Hepatitis C virus (isolate Japanese)) Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Although optimizing the resistance profile of an inhibitor can be challenging, it is potentially important for improving the long term effectiveness of antiviral therapy. This work describes our rational approach towards the identification of a macrocyclic acyl sulfonamide that is a potent inhibitor of the NS3-NS4A proteases of all HCV genotypes, and of a panel of genotype 1 resistant variants. The enhanced potency of this compound versus variants D168V and R155K facilitated X-ray determination of the inhibitor-variant complexes. In turn, these structural studies revealed a complex molecular basis of resistance, and rationalized how such compounds are able to circumvent these mechanisms. Molecular Mechanism by which a Potent Hepatitis C Virus NS3-NS4A Protease Inhibitor Overcomes Emergence of Resistance.,O'Meara JA, Lemke CT, Godbout C, Kukolj G, Lagace L, Moreau B, Thibeault D, White PW, Llinas-Brunet M J Biol Chem. 2012 Dec 27. PMID:23271737 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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