Transient kinetic analyses of the ribonuclease H cleavage activity of HIV-1 reverse transcriptase in complex with efavirenz and/or a β-thujaplicinol analogue

Biochemical Journal

Volumn 455, Issue 2, 2013, Pages 179-184

  Herman, Brian D ^a   Sluis Cremer, Nicolas ^a  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

Efavirenz; Non nucleoside; Reverse transcriptase; RNase H; RNase H inhibitor

Indexed keywords

2,7 DIHYDROXY 2,4,6 CYCLO HEPTATRIEN 1 ONE; 2,7 DIHYDROXY 4 METHYL 2,4,6 CYCLO HEPTATRIEN 1 ONE; DNA; DNA POLYMERASE; EFAVIRENZ; PRIMER DNA; RIBONUCLEASE H; RNA; RNA DIRECTED DNA POLYMERASE; THUJAPLICIN; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME KINETICS; GENE MUTATION; PRIORITY JOURNAL; STEADY STATE; STRUCTURE ACTIVITY RELATION;

ANTI-HIV AGENTS; BENZOXAZINES; BINDING SITES; HIV REVERSE TRANSCRIPTASE; KINETICS; REVERSE TRANSCRIPTASE INHIBITORS; RIBONUCLEASE H; TROPOLONE;

EID: 84884783608     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20130850     Document Type: Article

References (17)

1. Tramontano, E. and Di Santo, R. (2010) HIV-1 RT-associated RNase H function inhibitors: recent advances in drug development. Curr. Med. Chem. 17, 2837-2853
2. Budihas, S. R., Gorshkova, I., Gaidamakov, S., Wamiru, A., Bona, M. K., Parniak, M. A., Crouch, R. J., McMahon, J. B., Beutler, J. A. and Le Grice, S. F. (2005) Selective inhibition of HIV-1 reverse transcriptase-associated ribonuclease H activity by hydroxylated tropolones. Nucleic Acids Res. 33, 1249-1256
3. Himmel, D. M., Maegley, K. A., Pauly, T. A., Bauman, J. D., Das, K., Dharia, C., Clark, Jr, A. D., Ryan, K., Hickey, M. J., Love, R. A. et al. (2009) Structure of HIV-1 reverse transcriptase with the inhibitor ?-thujaplicinol bound at the RNase H active site. Structure 17, 1625-1635
4. Beilhartz, G. L., Wendeler, M., Baichoo, N., Rausch, J., Le Grice, S. and Gotte, M. (2009) HIV-1 reverse transcriptase can simultaneously engage its DNA/RNA substrate at both DNA polymerase and RNase H active sites: implications for RNase H inhibition. J. Mol. Biol. 388, 462-474
5. Shaw-Reid, C. A., Feuston, B., Munshi, V., Getty, K., Krueger, J., Hazuda, D. J., Parniak, M. A., Miller, M. D. and Lewis, D. (2005) Dissecting the effects of DNA polymerase and ribonuclease H inhibitor combinations on HIV-1 reverse-transcriptase activities. Biochemistry 44, 1595-1606
6. Hang, J. Q., Li, Y., Yang, Y., Cammack, N., Mirzadegan, T. and Klumpp, K. (2007) Substrate-dependent inhibition or stimulation of HIV RNase H activity by non-nucleoside reverse transcriptase inhibitors (NNRTIs). Biochem. Biophys. Res. Commun. 352, 341-350
7. Radzio, J. and Sluis-Cremer, N. (2008) Efavirenz accelerates HIV-1 reverse transcriptase ribonuclease H cleavage, leading to diminished zidovudine excision. Mol. Pharmacol. 73, 601-606
8. Abbondanzieri, E. A., Bokinsky, G., Rausch, J. W., Zhang, J. X., Le Grice, S. F. and Zhuang, X. (2008) Dynamic binding orientations direct activity of HIV reverse transcriptase. Nature 453, 184-189
9. Lapkouski, M., Tian, L., Miller, J. T., Le Grice, S. F. and Yang, ,W. (2013) Complexes of HIV-1 RT, NNRTI and RNA/DNA hybrid reveal a structure compatible with RNA degradation. Nat. Struct. Mol. Biol. 20, 230-236
10. Le Grice, S. F. and Gruninger-Leitch, F. (1990) Rapid purification of homodimer and heterodimer HIV-1 reverse transcriptase by metal chelate affinity chromatography. Eur. J. Biochem. 187, 307-314
11. Le Grice, S. F., Cameron, C. E. and Benkovic, S. J. (1995) Purification and characterization of human immunodeficiency virus type 1 reverse transcriptase. Methods Enzymol. 262, 130-144
12. Parniak, M. A., Min, K. L., Budihas, S. R., Le Grice, S. F. and Beutler, J,A. (2003) A fluorescence-based high-throughput screening assay for inhibitors of human immunodeficiency virus-1 reverse transcriptase-associated ribonuclease H activity. Anal. Biochem. 322, 33-39
13. Radzio, J. and Sluis-Cremer, N. (2011) Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase. Retrovirology 8, 69
14. Yap, S. H., Herman, B. D., Radzio, J., Sluis-Cremer, N. and Tachedjian, G. (2012) N348I in HIV-1 reverse transcriptase counteracts the synergy between zidovudine and nevirapine. J. Acquired Immune Defic. Syndr. 61, 153-157
15. Yap, S. H., Sheen, C. W., Fahey, J., Zanin, M., Tyssen, D., Lima, V. D., Wynhoven, B., Kuiper, M., Sluis-Cremer, N., Harrigan, P. R. and Tachedjian, G. (2007) N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. PLoS Med. 4, e335
16. Hachiya, A., Kodama, E. N., Sarafianos, S. G., Schuckmann, M. M., Sakagami, Y., Matsuoka, M., Takiguchi, M., Gatanaga, H. and Oka, S. (2008) Amino acid mutation N348I in the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase confers multiclass resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors. J. Virol. 82, 3261-3270
17. Ehteshami, M., Beilhartz, G. L., Scarth, B. J., Tchesnokov, E. P., McCormick, S., Wynhoven, B., Harrigan, P. R. and Gotte, M. (2008) Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3-azido-3-deoxythymidine through both RNase H-dependent and-independent mechanisms. J. Biol. Chem. 283, 22222-22232