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

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 with to the fingers and and the the polymerase in crystal to be the in crystal and in the have the structures of two at from the polymerase and in the thumb The in and the and can be in crystal and in of the the from the to the 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 with to the fingers and and the the polymerase in crystal to be the in crystal and in the have the structures of two at from the polymerase and in the thumb The in and the and can be in crystal and in of the the from the to the C virus (HCV) hepatitis C hepatitis C of the The virus in the of the to the of and in of of been the of to and of The of and with and the of to virus and of the and of HCV The of of The and The of structural and and and polymerase and the the in the and of the of in been RNA-dependent RNA polymerase in crystal structures of HCV polymerase genotype in forms have been determined. The with fingers, palm, and thumb HCV polymerase with other The of HCV polymerase in with been of HCV RNA polymerase and have the polymerase structural of the RNA-dependent RNA from and known of and of the polymerase from virus both and have been The thumb of the polymerase the the polymerases, RNA-dependent RNA polymerases, polymerases, RNA polymerases, and RNA-dependent of to have structural of the HCV from of the in the of the the crystal structures of the HCV polymerase genotype 2a from two crystal and of HCV polymerase have been and have the crystal structures of HCV polymerase genotype of to the of have the of HCV polymerase genotype 2a with two of have been The of the and of be in the of the The HCV polymerase genotype 2a in the of and and and of the of of the polymerase 2a the the HCV polymerase 2a from the and in of the The in two the the of of the the of the of of and polymerase the of the the and the of of of and the the of and at and of at and the and the to the the and the of the HCV polymerase 2a and from the and and in polymerase the polymerase with The polymerase and the of the polymerase the and and to of at and and crystal to and at of HCV genotype 2a the of the RNA The of the in of of of of of and of RNA-dependent RNA polymerase to at The the of of of of and of of at to the to of The The with of and at of and the The the and of HCV 2a the at of and with of in and and the of to crystal forms of the from crystal forms to the in the the crystal with the be to with the be to in and in to the the and the of of and in the and of of of and from of in in to the the and the of of and in the and of and in from both crystal forms and from the at the of the in from the with crystal forms in the with of and in and The and the and of both crystal forms and the in and of both crystal forms with the the 1b genotype polymerase the The structures the of the and from the of the the with the of the structures in the the the the to of and and at of and in the thumb of the in The The and the the to of of molecules in the in of at in and in of and of the and the of molecules in the and the The in in the the The the the from to The to of the of the in The of the of the structures of the of lie in the of the The in The have been in the and the and the and of at the of the of the in and in and of in and three-dimensional structures of the HCV polymerase genotype 2a in both crystal forms have the right-hand of fingers, palm, and thumb in HCV polymerase genotype 1b and in other the of the polymerase in from in The from the fingers and structural in both The of of between the two molecules with the of The in in of The of the of in the of the of the of in The in from The and of the and in the between the from the fingers and the thumb of the in the polymerase in The of at the interface in the in the in The in the in and the differences the molecules structures in of the crystal the molecules in the crystal have the of the in both crystal HCV polymerase genotype 1b the of to in to in the structural the to the of HCV polymerase genotype 2a other RNA the polymerase of HCV genotype of the of HCV polymerase genotype 2a in crystal and to the fingers, palm, and thumb The two from the fingers in the fingers and in The the of molecules in both crystal the differences between the and the the in the in in with of between the from the fingers and thumb of the molecules in crystal forms and The of between the in in of between molecules in and at the fingers and thumb in main in main in main in main main main in the and the fingers structural in the the The and and the in both The of the between the two forms The of the structural and the between two structural in the thumb the main between and of of the thumb relative to the fingers and domains. known the thumb the of the in virus and between the two molecules in the and of the RNA-dependent RNA polymerase of the virus of the thumb the in been to with RNA HCV polymerase genotype 2a can have of 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to and of The of and with and the of to HCV virus and of the and of HCV The of of The and The of structural and and and polymerase and the the in the and of the of in been RNA-dependent RNA polymerase in crystal structures of HCV polymerase genotype in forms have been determined. 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Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.