1yv2
Hepatitis C virus NS5B RNA-dependent RNA Polymerase genotype 2a
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OverviewOverview
Crystal structures of the RNA-dependent RNA polymerase genotype 2a of, hepatitis C virus (HCV) from two crystal forms have been determined., Similar to the three-dimensional structures of HCV polymerase genotype 1b, and other known polymerases, the structures of the HCV polymerase genotype, 2a in both crystal forms can be depicted in the classical right-hand, arrangement with fingers, palm, and thumb domains. The main structural, differences between the molecules in the two crystal forms lie at the, interface of the fingers and thumb domains. The relative orientation of, the thumb domain with respect to the fingers and palm domains and the, beta-flap region is altered. Structural analysis reveals that the NS5B, polymerase in crystal form I adopts a "closed" conformation that is, believed to be the active form, whereas NS5B in crystal form II adopts an, "open" conformation and is thus in the inactive form. In addition, we have, determined the structures of two NS5B polymerase/non-nucleoside inhibitor, complexes. Both inhibitors bind at a common binding site, which is nearly, 35 A away from the polymerase active site and is located in the thumb, domain. The binding pocket is predominantly hydrophobic in nature, and the, enzyme inhibitor complexes are stabilized by hydrogen bonding and van der, Waals interactions. Inhibitors can only be soaked in crystal form I and, not in form II; examination of the enzyme-inhibitor complex reveals that, the enzyme has undergone a dramatic conformational change from the form I, (active) complex to the form II (inactive).
About this StructureAbout this Structure
1YV2 is a Single protein structure of sequence from Hepatitis c virus with SO4 and GOL as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of the RNA-dependent RNA polymerase genotype 2a of hepatitis C virus reveal two conformations and suggest mechanisms of inhibition by non-nucleoside inhibitors., Biswal BK, Cherney MM, Wang M, Chan L, Yannopoulos CG, Bilimoria D, Nicolas O, Bedard J, James MN, J Biol Chem. 2005 May 6;280(18):18202-10. Epub 2005 Mar 2. PMID:15746101
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