2who

CRYSTAL STRUCTURE OF HEPATITIS C VIRUS NS5B POLYMERASE FROM 1B GENOTYPE IN COMPLEX WITH A NON-NUCLEOSIDE INHIBITORCRYSTAL STRUCTURE OF HEPATITIS C VIRUS NS5B POLYMERASE FROM 1B GENOTYPE IN COMPLEX WITH A NON-NUCLEOSIDE INHIBITOR

Structural highlights 2who is a 2 chain structure with sequence from Hepatitis c virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Related: 1nhu, 2i1r, 2wcx, 1jxp, 1gx6, 2jc1, 8ohm, 1c2p, 1a1q, 1cu1, 1bt7, 2jc0, 2ax1, 1ns3, 1csj, 1nhv, 1gx5, 2brk, 2brl, 2ax0, 2awz, 1quv, 1os5 Activity: RNA-directed RNA polymerase, with EC number 2.7.7.48 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed The hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRp) plays a central role in virus replication. NS5B has no functional equivalent in mammalian cells and, as a consequence, is an attractive target for inhibition. Herein, we present 1H-benzo[de]isoquinoline-1,3(2H)-diones as a new series of selective inhibitors of HCV NS5B polymerase. The HTS hit 1 shows submicromolar potency in two different HCV replicons (1b and 2b) and displays no activity on other polymerases (HIV-RT, Polio-pol, GBV-b-pol). These inhibitors act during the pre-elongation phase by binding to NS5B non-nucleoside binding site Thumb Site II as demonstrated by crystal structure of compound 1 with the DeltaC55-1b and DeltaC21-2b enzymes and by mutagenesis studies. SAR in this new series reveals inhibitors, such as 20, with low micromolar activity in the HCV replicon and with good activity/toxicity window in cells. Identification and Biological Evaluation of a Series of 1H-Benzo[de]isoquinoline-1,3(2H)-diones as Hepatitis C Virus NS5B Polymerase Inhibitors (double dagger).,Ontoria JM, Rydberg EH, Di Marco S, Tomei L, Attenni B, Malancona S, Martin Hernando JI, Gennari N, Koch U, Narjes F, Rowley M, Summa V, Carroll SS, Olsen DB, De Francesco R, Altamura S, Migliaccio G, Carfi A J Med Chem. 2009 Aug 27;52(16):5217-27. PMID:19877603 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also RNA polymerase

spinqualitylabelsall models 2who, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image