Publication: NMR characterization of HIV-1 reverse transcriptase binding to various non-nucleoside reverse transcriptase inhibitors with different activities
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Issued Date
2015
Resource Type
File Type
application/pdf
ISSN
20452322
Other identifier(s)
2-s2.0-84946129824
Rights Holder(s)
Scopus
Bibliographic Citation
Scientific Reports. Vol 5, (2015)
Suggested Citation
Thammaporn R., Yagi-Utsumi M., Yamaguchi T., Boonsri P., Saparpakorn P., Choowongkomon K., Techasakul S., Kato K., Hannongbua S. NMR characterization of HIV-1 reverse transcriptase binding to various non-nucleoside reverse transcriptase inhibitors with different activities. Scientific Reports. Vol 5, (2015). doi:10.1038/srep15806 Retrieved from: https://hdl.handle.net/20.500.14740/6041
Abstract
Human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is an important target for antiviral therapy against acquired immunodeficiency syndrome. However, the efficiency of available drugs is impaired most typically by drug-resistance mutations in this enzyme. In this study, we applied a nuclear magnetic resonance (NMR) spectroscopic technique to the characterization of the binding of HIV-1 RT to various non-nucleoside reverse transcriptase inhibitors (NNRTIs) with different activities, i.e., nevirapine, delavirdine, efavirenz, dapivirine, etravirine, and rilpivirine. 1 H- 13 C heteronuclear single-quantum coherence (HSQC) spectral data of HIV-1 RT, in which the methionine methyl groups of the p66 subunit were selectively labeled with 13 C, were collected in the presence and absence of these NNRTIs. We found that the methyl 13 C chemical shifts of the M230 resonance of HIV-1 RT bound to these drugs exhibited a high correlation with their anti-HIV-1 RT activities. This methionine residue is located in proximity to the NNRTI-binding pocket but not directly involved in drug interactions and serves as a conformational probe, indicating that the open conformation of HIV-1 RT was more populated with NNRTIs with higher inhibitory activities. Thus, the NMR approach offers a useful tool to screen for novel NNRTIs in developing anti-HIV drugs.
Subject(s)
Protein binding
Reverse transcriptase, Human immunodeficiency virus 1
RNA directed DNA polymerase
RNA directed DNA polymerase inhibitor
Antagonists and inhibitors
Binding site
Chemistry
Enzymology
Human
Human immunodeficiency virus 1
Nuclear magnetic resonance
Binding Sites
HIV Reverse Transcriptase
HIV-1
Humans
Nuclear Magnetic Resonance, Biomolecular
Protein Binding
Reverse Transcriptase Inhibitors
Reverse transcriptase, Human immunodeficiency virus 1
RNA directed DNA polymerase
RNA directed DNA polymerase inhibitor
Antagonists and inhibitors
Binding site
Chemistry
Enzymology
Human
Human immunodeficiency virus 1
Nuclear magnetic resonance
Binding Sites
HIV Reverse Transcriptase
HIV-1
Humans
Nuclear Magnetic Resonance, Biomolecular
Protein Binding
Reverse Transcriptase Inhibitors