کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2187110 | 1096097 | 2009 | 14 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Binding of a Noncovalent Inhibitor Exploiting the S′ region Stabilizes the Hepatitis C virus NS3 Protease Conformation in the Absence of Cofactor Binding of a Noncovalent Inhibitor Exploiting the S′ region Stabilizes the Hepatitis C virus NS3 Protease Conformation in the Absence of Cofactor](/preview/png/2187110.png)
SummaryWe present the first structure of a noncovalent inhibitor bound to the protease domain of hepatitis C virus NS3 protein (NS3p), solved by NMR. The inhibitor exploits interactions with the S′ region of NS3p to form a long-lived complex, although the absence of negative charges strongly reduces the association rate. The inhibitor stabilizes the N-terminal domain of NS3p and the substrate-binding site, and correctly aligns catalytic His-Asp residues. These actions were previously attributed exclusively to the cofactor NS4A, which interacts with the N-terminal domain of the NS3p and functions as an activator in vivo. The structure of the inhibitor/NS3p complex is very similar to that of the NS3p–NS4A complex, showing that binding of the NS4A cofactor is not the only event leading to a stable active-site conformation.
Journal: Journal of Molecular Biology - Volume 385, Issue 4, 30 January 2009, Pages 1142–1155