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Basic Characteristics of Mutations
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Mutation Site
|
G48A |
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Mutation Site Sentence
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The third alteration disrupted the stem II in structure A by simultaneously introducing mutations G47A and G48A. |
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Mutation Level
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Nucleotide level |
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Mutation Type
|
Nonsynonymous substitution |
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Gene/Protein/Region
|
RT |
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Standardized Encoding Gene
|
gag-pol:155348
|
|
Genotype/Subtype
|
HIV-1 |
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Viral Reference
|
HXB2
|
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Functional Impact and Mechanisms
|
|
Disease
|
-
|
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Immune
|
- |
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Target Gene
|
-
|
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Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
- |
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Literature Information
|
|
PMID
|
17644816
|
|
Title
|
Active site binding and sequence requirements for inhibition of HIV-1 reverse transcriptase by the RT1 family of single-stranded DNA aptamers
|
|
Author
|
Kissel JD,Held DM,Hardy RW,Burke DH
|
|
Journal
|
Nucleic acids research
|
|
Journal Info
|
2007;35(15):5039-50
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Abstract
|
Nucleic acid aptamers can potentially be developed as broad-spectrum antiviral agents. Single-stranded DNA (ssDNA) aptamer RT1t49 inhibits reverse transcriptases (RT) from HIV-1 and diverse lentiviral subtypes with low nanomolar values of Kd and IC50. To dissect the structural requirements for inhibition, RT-catalyzed DNA polymerization was measured in the presence of RT1t49 variants. Three structural domains were found to be essential for RT inhibition by RT1t49: a 5' stem (stem I), a connector and a 3' stem (stem II) capable of forming multiple secondary structures. Stem I tolerates considerable sequence plasticity, suggesting that it is recognized by RT more by structure than by sequence-specific contacts. Truncating five nucleotides from the 3' end prevents formation of the most stable stem II structure, yet has little effect on IC50 across diverse HIV-1, HIV-2 and SIV(CPZ) RT. When bound to wild-type RT or an RNase H active site mutant, site-specifically generated hydroxyl radicals cleave after nucleotide A32. Cleavage is eliminated by either of two polymerase (pol)-active site mutants, strongly suggesting that A32 lies within the RT pol-active site. These data suggest a model of ssDNA aptamer-RT interactions and provide an improved molecular understanding of a potent, broad-spectrum ssDNA aptamer.
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Sequence Data
|
-
|