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Interaction kinetic...
Interaction kinetic characterization of HIV-1 reverse transcriptase non-nucleoside inhibitor resistance
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- Geitmann, Matthis (författare)
- Uppsala universitet,Institutionen för naturvetenskaplig biokemi
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- Unge, Torsten (författare)
- Uppsala universitet,Strukturell molekylärbiologi
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- Danielson, U. Helena (författare)
- Uppsala universitet,Institutionen för naturvetenskaplig biokemi
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(creator_code:org_t)
- 2006-03-25
- 2006
- Engelska.
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 49:8, s. 2375-87
- Relaterad länk:
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http://www.ncbi.nlm....
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visa fler...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- To decipher the mechanism for non-nucleoside inhibitor resistance of HIV-1 reverse transcriptase, the kinetics of the interaction between wild type and drug-resistant variants of the enzyme and structurally diverse inhibitors were determined. Substitution of amino acid residues in the inhibitor binding site resulted in altered rate constants for the pre-equilibrium between two unliganded forms of the enzyme, and for the association and dissociation of the inhibitor-enzyme interaction. The Y181C, V108I, and P225H substitutions affected primarily the association and dissociation rate constants, while the K103N and the L100I substitutions also influenced the equilibrium between the two forms of the free enzyme. The K103N and the L100I substitutions were found to facilitate both the entry of the inhibitor into the binding pocket as well as its exit, in contrast to what has been reported elsewhere. Interaction kinetic-based resistance profiles showed that phenethylthiazolylthiourea compounds were relatively insensitive to the studied substitutions.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- Binding Sites
- Biosensing Techniques/methods
- Crystallography; X-Ray
- Drug Resistance; Viral
- Enzyme Activation/drug effects
- HIV-1 Reverse Transcriptase/*antagonists & inhibitors/chemistry
- Kinetics
- Molecular Structure
- Protein Conformation
- Protein Structure; Tertiary
- Reverse Transcriptase Inhibitors/chemistry/*pharmacology
- Structure-Activity Relationship
- Cell and molecular biology
- Cell- och molekylärbiologi
- Biochemistry
- Biokemi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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