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Basic Characteristics of Mutations
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Mutation Site
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E35G |
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Mutation Site Sentence
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Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D G S mutant in the South African HIV-1 subtype C proteaseHerein, we report the effect of nine FDA approved protease inhibitor drugs against a new HIV-1 subtype C mutant protease, E35D G S. |
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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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PR |
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Standardized Encoding Gene
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gag-pol
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Genotype/Subtype
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HIV-1 |
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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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Cell line
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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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PIs |
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Location
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- |
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Literature Information
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PMID
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31409143
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Title
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Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D upward arrowG upward arrowS mutant in the South African HIV-1 subtype C protease
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Author
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Maseko S,Padayachee E,Maphumulo S,Govender T,Sayed Y,Maguire G,Lin J,Naicker T,Baijnath S,Gerhardus KH
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Journal
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Journal of enzyme inhibition and medicinal chemistry
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Journal Info
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2019 Dec;34(1):1451-1456
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Abstract
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Herein, we report the effect of nine FDA approved protease inhibitor drugs against a new HIV-1 subtype C mutant protease, E35D upward arrowG upward arrowS. The mutant has five mutations, E35D, two insertions, position 36 (G and S), and D60E. Kinetics, inhibition constants, vitality, Gibbs free binding energies are reported. The variant showed a decreased affinity for substrate and low catalytic efficiency compared to the wild type. There was a significant decrease in the binding of seven FDA approved protease inhibitors against the mutant (p < .0001). Amprenavir and ritonavir showed the least decrease, but still significant reduced activity in comparison to the wildtype (4 and 5 folds, respectively, p = .0021 and .003, respectively). Nelfinavir and atazanavir were the worst inhibitors against the variant as seen from the IC(50), with values of 1401 +/- 3.0 and 685 +/- 3.0 nM, respectively. Thermodynamics data showed less favourable Gibbs free binding energies for the protease inhibitors to the mutant.
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Sequence Data
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-
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