Inhibition of the ribonuclease H activity of HIV-1 reverse transcriptase by GSK5750 correlates with slow enzyme-inhibitor dissociation

Journal of Biological Chemistry

Volumn 289, Issue 23, 2014, Pages 16270-16277

  Beilhartz, Greg L ^a   Ngure, Marianne ^a   Johns, Brian A ^b   Deanda, Felix ^b   Gerondelis, Peter ^b   Götte, Matthias ^a  

^a MCGILL UNIVERSITY   (Canada)

^b GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DISSOCIATION; ESCHERICHIA COLI; NUCLEIC ACIDS; VIRUSES;

ASSOCIATION KINETICS; DNA SYNTHESISS; ENZYME-SUBSTRATE COMPLEXES; EQUILIBRIUM DISSOCIATION CONSTANT; HIV-1 REVERSE TRANSCRIPTASE; HUMAN IMMUNODEFICIENCY VIRUS TYPE-1; KINETIC BEHAVIOR; REVERSE TRANSCRIPTASES;

ENZYME INHIBITION;

BETA THUJAPLICINOL; ESTERASE INHIBITOR; GSK 5750; MAGNESIUM ION; MOLECULAR SCAFFOLD; RIBONUCLEASE H; RIBONUCLEASE INHIBITOR; RNA DIRECTED DNA POLYMERASE; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; COMPLEX FORMATION; CONTROLLED STUDY; DISSOCIATION CONSTANT; DNA SYNTHESIS; DRUG PROTEIN BINDING; DRUG STRUCTURE; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME SPECIFICITY; ENZYME SUBSTRATE COMPLEX; ESCHERICHIA COLI; PRIORITY JOURNAL;

DRUG DEVELOPMENT; HIV-1; RETROVIRUS; REVERSE TRANSCRIPTION; RIBONUCLEASE;

BASE SEQUENCE; HIV REVERSE TRANSCRIPTASE; KINETICS; OLIGODEOXYRIBONUCLEOTIDES; PYRIDINES; PYRIMIDINONES; REVERSE TRANSCRIPTASE INHIBITORS; RIBONUCLEASE H;

EID: 84902126185     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M114.569707     Document Type: Article

References (36)

1. Telesnitsky, A., and Goff, S. (eds) (1997) Retroviruses, pp. 121-160, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY
2. Davies, J. F., 2nd, Hostomska, Z., Hostomsky, Z., Jordan, S. R., and Matthews, D. A. (1991) Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase. Science 252, 88-95
3. Huang, H., Chopra, R., Verdine, G. L., and Harrison, S. C. (1998) Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance. Science 282, 1669-1675
4. Jacobo-Molina, A., Ding, J., Nanni, R. G., Clark, A. D., Jr., Lu, X., Tantillo, C., Williams, R. L., Kamer, G., Ferris, A. L., and Clark, P. (1993) Crystal structure of human immunodeficiency virus type 1 reverse transcriptase complexed with double-stranded DNA at 3.0 A resolution shows bent DNA. Proc. Natl. Acad. Sci. U. S. A. 90, 6320-6324
5. Sarafianos, S. G., Das, K., Tantillo, C., Clark, A. D., Jr., Ding, J., Whitcomb, J. M., Boyer, P. L., Hughes, S. H., and Arnold, E. (2001) Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA: DNA. EMBO J. 20, 1449-1461
6. De Clercq, E. (2007) The designof drugs for HIV and HCV. Nat. Rev. Drug Discov. 6, 1001-1018
7. Kohlstaedt, L. A., Wang, J., Friedman, J. M., Rice, P. A., and Steitz, T. A. (1992) Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 256, 1783-1790
8. Gopalakrishnan, V., Peliska, J. A., and Benkovic, S. J. (1992) Human immunodeficiency virus type 1 reverse transcriptase: spatial and temporal relationship between the polymerase and RNase H activities. Proc. Natl. Acad. Sci. U. S. A. 89, 10763-10767
9. Götte, M., Fackler, S., Hermann, T., Perola, E., Cellai, L., Gross, H. J., Le Grice, S. F., and Heumann, H. (1995) HIV-1 reverse transcriptase-associated RNase H cleaves RNA/RNA in arrested complexes: implications for the mechanism by which RNase H discriminates between RNA/RNA and RNA/DNA. EMBO J. 14, 833-841
10. Beilhartz, G. L., Wendeler, M., Baichoo, N, Rausch, J., Le Grice, S., and Götte, 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
11. Marchand, B., and Götte, M. (2003) Site-specific footprinting reveals differences in the translocation status of HIV-1 reverse transcriptase. Implications for polymerase translocation and drug resistance. J. Biol. Chem. 278, 35362-35372
12. Furfine, E. S., and Reardon, J. E. (1991) Reverse transcriptase. RNase H from the human immunodeficiency virus. Relationship of the DNA polymerase and RNA hydrolysis activities. J. Biol. Chem. 266, 406-412
13. Schultz, S. J., and Champoux, J. J. (2008) RNase H activity: structure, specificity, and function in reverse transcription. Virus Res. 134, 86-103
14. Fuentes, G. M., Rodríguez-Rodríguez, L., Fay, P. J., and Bambara, R. A. (1995) Use of an oligoribonucleotide containing the polypurine tract sequence as a primer by HIV reverse transcriptase. J. Biol. Chem. 270, 28169-28176
15. Götte, M., Maier, G., Onori, A. M., Cellai, L., Wainberg, M. A., and Heumann, H. (1999) Temporal coordination between initiation of HIV (+) - strand DNA synthesis and primer removal. J. Biol. Chem. 274, 11159-11169
16. Huber, H. E., and Richardson, C. C. (1990) Processing of the primer for plus strand DNA synthesis by human immunodeficiency virus 1 reverse transcriptase. J. Biol. Chem. 265, 10565-10573
17. Palaniappan, C, Fay, P. J., and Bambara, R. A. (1995) Nevirapine alters the cleavage specificity of ribonuclease H of human immunodeficiency virus 1 reverse transcriptase. J. Biol. Chem. 270, 4861-4869
18. Pullen, K. A., and Champoux, J. J. (1990) Plus-strand origin for human immunodeficiency virus type 1: implications for integration. J. Virol. 64, 6274-6277
19. Smith, J. S., and Roth, M. J. (1992) Specificity of human immunodeficiency virus-1 reverse transcriptase-associated ribonuclease H in removal of the minus-strand primer, tRNA (Lys3). J. Biol. Chem. 267, 15071-15079
20. Beilhartz, G. L., and Götte, M. (2010) HIV-1 ribonuclease H: structure, catalytic mechanism and inhibitors. Viruses 2, 900-926
21. 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
22. Himmel, D. M., Maegley, K. A., Pauly, T. A., Bauman, J. D., Das, K., Dharia, C., Clark, A. D., Jr., Ryan, K., Hickey, M. J., Love, R. A., Hughes, S. H, Bergqvist, S., and Arnold, E. (2009) Structure of HIV-1 reverse transcriptase with the inhibitorβ-thujaplicinol bound at the RNase H active site. Structure 17, 1625-1635
23. Kirschberg, T. A., Balakrishnan, M., Squires, N. H., Barnes, T., Brendza, K. M., Chen, X., Eisenberg, E. J., Jin, W., Kutty, N., Leavitt, S., Liclican, A., Liu, Q., Liu, X., Mak, J., Perry, J. K., Wang, M., Watkins, W. J., and Lansdon, E. B. (2009) RNase H active site inhibitors of human immunodeficiency virus type 1 reverse transcriptase: design, biochemical activity, and structural information. J. Med. Chem. 52, 5781-5784
24. Klumpp, K., and Mirzadegan, T. (2006) Recent progress in the design of small molecule inhibitors of HIV RNase H. Curr. Pharm. Des. 12, 1909-1922
25. Su, H. P., Yan, Y., Prasad, G. S., Smith, R. F., Daniels, C. L., Abeywickrema, P. D., Reid, J. C, Loughran, H. M., Kornienko, M., Sharma, S., Grobler, J. A., Xu, B., Sardana, V., Allison, T. J., Williams, P. D., Darke, P. L., Hazuda, D. J., and Munshi, S. (2010) Structural basis for the inhibition of RNase H activity of HIV-1 reverse transcriptase by RNase H active site-directed inhibitors. J. Virol. 84, 7625-7633
26. Arion, D., Sluis-Cremer, N., Min, K. L., Abram, M. E., Fletcher, R. S., and Parniak, M. A. (2002) Mutational analysis of Tyr-501 of HIV-1 reverse transcriptase: effects on ribonuclease H activity and inhibition of this activity by N-acylhydrazones. J. Biol. Chem. 277, 1370-1374
27. Himmel, D. M., Sarafianos, S. G., Dharmasena, S., Hossain, M. M., McCoy-Simandle, K., Ilina, T., Clark, A. D., Jr., Knight, J. L., Julias, J. G., Clark, P. K., Krogh-Jespersen, K., Levy, R. M., Hughes, S. H., Parniak, M. A., and Arnold, E. (2006) HIV-1 reverse transcriptase structure with RNase H inhibitor dihydroxy benzoyl naphthyl hydrazone bound at a novel site. ACS Chem. Biol. 1, 702-712
28. Chung, S., Wendeler, M., Rausch, J. W., Beilhartz, G., Gotte, M., O'Keefe, B. R., Bermingham, A., Beutler, J. A., Liu, S., Zhuang, X., and Le Grice, S. F. (2010) Structure-activity analysis of vinylogous urea inhibitors of human immunodeficiency virus-encoded ribonuclease H. Antimicrob. Agents Chemother. 54, 3913-3921
29. Wendeler, M., Lee, H. F., Bermingham, A., Miller, J. T., Chertov, O., Bona, M. K., Baichoo, N. S., Ehteshami, M., Beutler, J., O'Keefe, B. R., Götte, M., Kvaratskhelia, M., and Le Grice, S. (2008) Vinylogous ureas as a novel class of inhibitors of reverse transcriptase-associated ribonuclease H activity. ACS Chem. Biol. 3, 635-644
30. Kati, W. M., Johnson, K. A., Jerva, L. F., and Anderson, K. S. (1992) Mechanism and fidelity of HIV reverse transcriptase. J. Biol. Chem. 267, 25988-25997
31. Herman, B. D., and Sluis-Cremer, N. (2013) Transient kinetic analyses of the ribonuclease H cleavage activity of HIV-1 reverse transcriptase in complex with efavirenz and/or aβ-thujaplicinol analogue. Biochem. J. 455, 179-184
32. Le Grice, S. F., and Grüninger-Leitch, F. (1990) Rapid purification of homodimer and heterodimer HIV-1 reverse transcriptase by metal chelate affinity chromatography. Eur. J. Biochem. 187, 307-314
33. Garvey, E. P., Romines, K. R., and Boone, L. R. (2003) Discovery and Development of New HIV Medicines in AIDS and Other Manifestations of HIVInfection (Wormser, G. P., ed.), 4th Ed., pp. 855-866, Academic Press, San Diego
34. Burney, T., and Dusheiko, G. (2011) Overview of the PROVE studies evaluating the use of telaprevir in chronic hepatitis C genotype 1 patients. Expert Rev. Anti Infect. Ther. 9, 151-160
35. Foote, B. S., Spooner, L. M., and Belliveau, P. P. (2011) Boceprevir: a protease inhibitor for the treatment of chronic hepatitis C. Ann. Pharmacother. 45, 1085-1093
36. Lin, C. (2006) HCV NS3-4A serine protease in Hepatitis C Viruses: Genomes and Molecular Biology (Tan, S.-L., ed) pp. 163-206, Horizon Bioscience, Norfolk, UK