scholarly journals Probing Structural Changes among Analogous Inhibitor-Bound Forms of HIV-1 Protease and a Drug-Resistant Mutant in Solution by Nuclear Magnetic Resonance

Biochemistry ◽  
2018 ◽  
Vol 57 (10) ◽  
pp. 1652-1662 ◽  
Author(s):  
Shahid N. Khan ◽  
John D. Persons ◽  
Janet L. Paulsen ◽  
Michel Guerrero ◽  
Celia A. Schiffer ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Structural Changes ◽  
Resistant Mutant ◽  
Drug Resistant ◽  
Drug Resistant Mutant ◽  
Hiv 1 ◽  
Nuclear Magnetic

Elucidation of HIV‐1 5' Leader Secondary Structure Through Novel Long Range Nuclear Magnetic Resonance (NMR) Techniques

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Claudia Walker ◽  
Elisabeth Kan ◽  
Faith Davis ◽  
Jonathan Catazaro ◽  
Michael Summers
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Secondary Structure ◽  
Long Range ◽  
Nmr Techniques ◽  
Hiv 1 ◽  
Nuclear Magnetic

scholarly journals Molecular modeling of HIV-1 reverse transcriptase drug-resistant mutant strains: implications for the mechanism of polymerase action

1997 ◽  
Vol 10 (12) ◽  
pp. 1379-1383 ◽  
Author(s):  
M. B. Kroeger Smith ◽  
C. J. Michejda ◽  
S. H. Hughes ◽  
P. L. Boyer ◽  
P. A. Janssen ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Reverse Transcriptase ◽  
Resistant Mutant ◽  
Drug Resistant ◽  
Mutant Strains ◽  
Drug Resistant Mutant ◽  
Hiv 1

scholarly journals Competing transfer pathways in direct and indirect dynamic nuclear polarization magic anglespinning nuclear magnetic resonance experiments on HIV-1 capsid assemblies: implications for sensitivity and resolution

2021 ◽  
Vol 2 (1) ◽  
pp. 239-249
Author(s):  
Ivan V. Sergeyev ◽  
Caitlin M. Quinn ◽  
Jochem Struppe ◽  
Angela M. Gronenborn ◽  
Tatyana Polenova
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Dynamic Nuclear Polarization ◽  
Nuclear Polarization ◽  
Magic Angle Spinning ◽  
Magic Angle ◽  
Large Signal ◽  
Experimental Conditions ◽  
Hiv 1 ◽  
Nuclear Magnetic

Abstract. Dynamic nuclear polarization (DNP)-enhanced magic angle spinning (MAS) nuclear magnetic resonance (NMR) of biological systems is a rapidly growing field. Large signal enhancements make the technique particularly attractive for signal-limited cases, such as studies of complex biological assemblies or at natural isotopic abundance. However, spectral resolution is considerably reduced compared to ambient-temperature non-DNP spectra. Herein, we report a systematic investigation into sensitivity and resolution of 1D and 2D 13C-detected DNP MAS NMR experiments on HIV-1 CA capsid protein tubular assemblies. We show that the magnitude and sign of signal enhancement as well as the homogeneous line width are strongly dependent on the biradical concentration, the dominant polarization transfer pathway, and the enhancement buildup time. Our findings provide guidance for optimal choice of sample preparation and experimental conditions in DNP experiments.

scholarly journals Mechanism of Interaction of Novel Indolylarylsulfone Derivatives with K103N and Y181I Mutant HIV-1 Reverse Transcriptase in Complex with its Substrates

2011 ◽  
Vol 22 (3) ◽  
pp. 107-118 ◽  
Author(s):  
Alberta Samuele ◽  
Sara Bisi ◽  
Alexandra Kataropoulou ◽  
Giuseppe La Regina ◽  
Francesco Piscitelli ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Resistant Mutant ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Specific Effects ◽  
Steady State Kinetic ◽  
Drug Resistant Mutant ◽  
K103n Mutation ◽  
New Generation ◽  
Hiv 1

Background: Novel indolylarylsulfones (lASs), designed through rational structure-based molecular modelling and docking approaches, have been recently characterized as effective inhibitors of the wild-type and drug-resistant mutant HIV-1 reverse transcriptase (RT). Methods: Here, we studied the interaction of selected halo- and nitra-substituted IAS derivatives, with the RT enzyme carrying the single resistance mutations K103N and Y181I through steady-state kinetic experiments. Results: The studied compounds exhibited high selectivity to the mutant RT in complex with its substrates, behaving as uncompetitive inhibitors. The presence of the K103N mutation, and to a lesser extent the Y181I, stabilized the drug interactions with the viral RT, when both its substrates were bound. Conclusions: The characterization of these mutation-specific effects on inhibitor binding might be relevant to the design of more effective new generation non-nucleoside reverse transcriptase inhibitors, with better resilience towards drug resistant mutants.

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