1yvx

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{{STRUCTURE_1yvx| PDB=1yvx | SCENE= }}
{{STRUCTURE_1yvx| PDB=1yvx | SCENE= }}
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'''Hepatitis C Virus RNA Polymerase Genotype 2a In Complex With Non- Nucleoside Analogue Inhibitor'''
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===Hepatitis C Virus RNA Polymerase Genotype 2a In Complex With Non- Nucleoside Analogue Inhibitor===
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==Overview==
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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).
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{{ABSTRACT_PUBMED_15746101}}
==About this Structure==
==About this Structure==
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[[Category: Non-nucleoside inhibitor]]
[[Category: Non-nucleoside inhibitor]]
[[Category: Ns5b polymerase genotype 2a]]
[[Category: Ns5b polymerase genotype 2a]]
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Revision as of 01:16, 28 July 2008

Image:1yvx.png

Template:STRUCTURE 1yvx

Hepatitis C Virus RNA Polymerase Genotype 2a In Complex With Non- Nucleoside Analogue Inhibitor

Template:ABSTRACT PUBMED 15746101

About this Structure

1YVX is a Single protein structure of sequence from Hepatitis c virus. Full crystallographic information is available from OCA.

Reference

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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