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Basic Characteristics of Mutations
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Mutation Site
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S139A |
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Mutation Site Sentence
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The structures of both native and S139A holo-HCV NS3/4A protease domain were solved to high resolution. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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NS3-4A |
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Standardized Encoding Gene
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NS3-4A
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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HCV Infection
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Immune
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- |
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Target Gene
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-
|
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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18421139
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Title
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Key steps in the structure-based optimization of the hepatitis C virus NS3/4A protease inhibitor SCH503034
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Author
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Madison V,Prongay AJ,Guo Z,Yao N,Pichardo J,Fischmann T,Strickland C,Myers J Jr,Weber PC,Beyer BM,Ingram R,Hong Z,Prosise WW,Ramanathan L,Taremi SS,Yarosh-Tomaine T,Zhang R,Senior M,Yang RS,Malcolm B,Arasappan A,Bennett F,Bogen SL,Chen K,Jao E,Liu YT,Lovey RG,Saksena AK,Venkatraman S,Girijavallabhan V,Njoroge FG
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Journal
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Journal of synchrotron radiation
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Journal Info
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2008 May;15(Pt 3):204-7
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Abstract
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The structures of both native and S139A holo-HCV NS3/4A protease domain were solved to high resolution. Subsequently, structures were determined for a series of ketoamide inhibitors in complex with the protease. The changes in the inhibitor potency were correlated with changes in the buried surface area upon binding the inhibitor to the active site. The largest contributions to the binding energy arise from the hydrophobic interactions of the P1 and P2 groups as they bind to the S1 and S2 pockets. This correlation of the changes in potency with increased buried surface area contributed directly to the design of a potent tripeptide inhibitor of the HCV NS3/4A protease, which is currently in clinical trials.
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Sequence Data
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-
|
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