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Basic Characteristics of Mutations
|
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Mutation Site
|
M204V |
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Mutation Site Sentence
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Molecular modeling studies of adefovir diphosphate with the wild type and the mutant HBV polymerase-DNA complex demonstrated that the increase in adefovir sensitivity toward HBV polymerase mutants (rtL180M, rtM204V/I, rtL180M-M204V/I) is a result of increased van der Waals interaction and is supplemented by the decreased affinity of natural substrate toward the mutant HBV polymerase. |
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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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RT |
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Standardized Encoding Gene
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P
|
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Genotype/Subtype
|
- |
|
Viral Reference
|
-
|
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Functional Impact and Mechanisms
|
|
Disease
|
Hepatitis B Virus Infection
|
|
Immune
|
- |
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Target Gene
|
-
|
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Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
Abacavir(ADV) |
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Location
|
- |
|
Literature Information
|
|
PMID
|
15261293
|
|
Title
|
Molecular mechanisms of adefovir sensitivity and resistance in HBV polymerase mutants: a molecular dynamics study
|
|
Author
|
Yadav V,Chu CK
|
|
Journal
|
Bioorganic & medicinal chemistry letters
|
|
Journal Info
|
2004 Aug 16;14(16):4313-7
|
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Abstract
|
Molecular modeling studies of adefovir diphosphate with the wild type and the mutant HBV polymerase-DNA complex demonstrated that the increase in adefovir sensitivity toward HBV polymerase mutants (rtL180M, rtM204V/I, rtL180M-M204V/I) is a result of increased van der Waals interaction and is supplemented by the decreased affinity of natural substrate toward the mutant HBV polymerase. In the case of rtN236T mutant, loss of two hydrogen bonds accompanied by significant decrease in electrostatic interactions is observed, which explains the observed decrease in drug sensitivity and binding affinity of adefovir diphosphate toward the rtN236T mutant HBV polymerase.
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Sequence Data
|
-
|