Structural basis for the inhibition of RNase H activity of HIV-1 reverse transcriptase by RNase H active site-directed inhibitors

Journal of Virology

Volumn 84, Issue 15, 2010, Pages 7625-7633

  Su, Hua Poo ^a   Yan, Youwei ^a   Prasad, G Sridhar ^a   Smith, Robert F ^a   Daniels, Christopher L ^a   Abeywickrema, Pravien D ^a   Reid, John C ^a   Loughran, H Marie ^a   Kornienko, Maria ^a   Sharma, Sujata ^a   Grobler, Jay A ^a   Xu, Bei ^a   Sardana, Vinod ^a   Allison, Timothy J ^a   Williams, Peter D ^a   Darke, Paul L ^a   Hazuda, Daria J ^a   Munshi, Sanjeev ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

METAL ION; NAPHTHYRIDINONE; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; PYRIDINE DERIVATIVE; RIBONUCLEASE H; RNA DIRECTED DNA POLYMERASE; UNCLASSIFIED DRUG;

ARTICLE; BINDING SITE; CATALYSIS; CRYSTAL STRUCTURE; CYTOTOXICITY; DENATURATION; ENZYME ACTIVITY; ENZYME BINDING; ENZYME INHIBITION; IC 50; PHARMACOPHORE; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROTEIN DOMAIN; STRUCTURE ANALYSIS; THERMAL ANALYSIS;

BINDING SITES; CATALYTIC DOMAIN; CATIONS; CRYSTALLOGRAPHY, X-RAY; ENZYME INHIBITORS; HIV; HIV REVERSE TRANSCRIPTASE; HIV-1; HUMANS; METALS; MODELS, MOLECULAR; NAPHTHYRIDINES; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY; RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 77954521861     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.00353-10     Document Type: Article

References (39)

1. Borkow, G., R. S. Fletcher, J. Barnard, D. Arion, D. Motakis, G. I. Dmitrienko, and M. A. Parniak. 1997. Inhibition of the ribonuclease H and DNA polymerase activities of HIV-1 reverse transcriptase by N-(4-tert-butylbenzoyl)- 2-hydroxy-1-naphthaldehyde hydrazone. Biochemistry 36:3179-3185.
2. Cerritelli, S. M., and R. J. Crouch. 2009. Ribonuclease H: the enzymes in eukaryotes. FEBS J. 276:1494-1505.
3. Cerritelli, S. M., E. G. Frolova, C. Feng, A. Grinberg, P. E. Love, and R. J. Crouch. 2003. Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1-null mice. Mol. Cell 11:807-815.
4. Cristofaro, J. V., J. W. Rausch, S. F. Le Grice, and J. J. DeStefano. 2002. Mutations in the ribonuclease H active site of HIV-RT reveal a role for this site in stabilizing enzyme-primer-template binding. Biochemistry 41:10968-10975.
5. Crow, Y. J., A. Leitch, B. E. Hayward, A. Garner, R. Parmar, E. Griffith, M. Ali, C. Semple, J. Aicardi, R. Babul-Hirji, C. Baumann, P. Baxter, E. Bertini, K. E. Chandler, D. Chitayat, D. Cau, C. Dery, E. Fazzi, C. Goizet, M. D. King, J. Klepper, D. Lacombe, G. Lanzi, H. Lyall, M. L. Martinez-Frias, M. Mathieu, C. McKeown, A. Monier, Y. Oade, O. W. Quarrell, C. D. Rittey, R. C. Rogers, A. Sanchis, J. B. Stephenson, U. Tacke, M. Till, J. L. Tolmie, P. Tomlin, T. Voit, B. Weschke, C. G. Woods, P. Lebon, D. T. Bonthron, C. P. Ponting, and A. P. Jackson. 2006. Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutieres syndrome and mimic congenital viral brain infection. Nat. Genet. 38:910-916.
6. Cummings, M. D., M. A. Farnum, and M. I. Nelen. 2006. Universal screening methods and applications of ThermoFluor. J. Biomol. Screen. 11:854-863.
7. Davies, J. F., II, Z. Hostomska, Z. Hostomsky, S. R. Jordan, and D. A. Matthews. 1991. Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase. Science 252:88-95. (Pubitemid 21916941)
8. DeLano, W. L. 2002. The PyMOL molecular graphics system. DeLano Scientific, San Carlos, CA. http://www.pymol.org.
9. DHHS. 2008. HIV and its treatment: what you should know. U.S. Department of Health and Human Services, Washington, DC.
10. Emsley, P., and K. Cowtan. 2004. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60:2126-2132.
11. Fields, B. N., D. M. Knipe, and P. M. Howley. 1996. Fields virology, 3rd ed. Lippincott-Raven Publishers, Philadelphia, PA.
12. Hansen, J., T. Schulze, W. Mellert, and K. Moelling. 1988. Identification and characterization of HIV-specific RNase H by monoclonal antibody. EMBO J. 7:239-243.
13. Hansen, J., T. Schulze, and K. Moelling. 1987. RNase H activity associated with bacterially expressed reverse transcriptase of human T-cell lymphotropic virus III/lymphadenopathy-associated virus. J. Biol. Chem. 262:12393-12396.
14. Hazuda, D. J., N. J. Anthony, R. P. Gomez, S. M. Jolly, J. S. Wai, L. Zhuang, T. E. Fisher, M. Embrey, J. P. Guare, Jr., M. S. Egbertson, J. P. Vacca, J. R. Huff, P. J. Felock, M. V. Witmer, K. A. Stillmock, R. Danovich, J. Grobler, M. D. Miller, A. S. Espeseth, L. Jin, I. W. Chen, J. H. Lin, K. Kassahun, J. D. Ellis, B. K. Wong, W. Xu, P. G. Pearson, W. A. Schleif, R. Cortese, E. Emini, V. Summa, M. K. Holloway, and S. D. Young. 2004. A naphthyridine carboxamide provides evidence for discordant resistance between mechanistically identical inhibitors of HIV-1 integrase. Proc. Natl. Acad. Sci. U. S. A. 101:11233-11238.
15. Himmel, D. M., K. A. Maegley, T. A. Pauly, J. D. Bauman, K. Das, C. Dharia, A. D. Clark, Jr., K. Ryan, M. J. Hickey, R. A. Love, S. H. Hughes, S. Bergqvist, and E. Arnold. 2009. Structure of HIV-1 reverse transcriptase with the inhibitor beta-Thujaplicinol bound at the RNase H active site. Structure 17:1625-1635.
16. Himmel, D. M., S. G. Sarafianos, S. Dharmasena, M. M. Hossain, K. McCoy-Simandle, T. Ilina, A. D. Clark, Jr., J. L. Knight, J. G. Julias, P. K. Clark, K. Krogh-Jespersen, R. M. Levy, S. H. Hughes, M. A. Parniak, and E. Arnold. 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.
17. Julias, J. G., M. J. McWilliams, S. G. Sarafianos, E. Arnold, and S. H. Hughes. 2002. Mutations in the RNase H domain of HIV-1 reverse transcriptase affect the initiation of DNA synthesis and the specificity of RNase H cleavage in vivo. Proc. Natl. Acad. Sci. U. S. A. 99:9515-9520.
18. Kirschberg, T. A., M. Balakrishnan, N. H. Squires, T. Barnes, K. M. Brendza, X. Chen, E. J. Eisenberg, W. Jin, N. Kutty, S. Leavitt, A. Liclican, Q. Liu, X. Liu, J. Mak, J. K. Perry, M. Wang, W. J. Watkins, and E. B. Lansdon. 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.
19. Kohlstaedt, L. A., J. Wang, J. M. Friedman, P. A. Rice, and T. A. Steitz. 1992. Crystal structure at 3.5 Å resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 256:1783-1790.
20. Kovacic, P. 2008. Does structural commonality of metal complex formation by PAC-1 (anticancer), DHBNH (anti-HIV), AHL (autoinducer), and UCS1025A (anticancer) denote mechanistic similarity? Signal transduction and medical aspects. J. Recept. Signal Transduct. Res. 28:141-152.
21. Laskowski, R. A., D. S. Moss, and J. M. Thornton. 1993. PROCHECK: a program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 26:283-291.
22. Lindberg, J., S. Sigurdsson, S. Lowgren, H. O. Andersson, C. Sahlberg, R. Noreen, K. Fridborg, H. Zhang, and T. Unge. 2002. Structural basis for the inhibitory efficacy of efavirenz (DMP-266), MSC194 and PNU142721 toward the HIV-1 RT K103N mutant. Eur. J. Biochem. 269:1670-1677.
23. Martin, J. L., J. E. Wilson, R. L. Haynes, and P. A. Furman. 1993. Mechanism of resistance of human immunodeficiency virus type 1 to 2′,3′-dideoxyinosine. Proc. Natl. Acad. Sci. U. S. A. 90:6135-6139.
24. Merluzzi, V. J., K. D. Hargrave, M. Labadia, K. Grozinger, M. Skoog, J. C. Wu, C. K. Shih, K. Eckner, S. Hattox, J. Adams, et al. 1990. Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor. Science 250:1411-1413.
25. Mizrahi, V., R. L. Brooksbank, and N. C. Nkabinde. 1994. Mutagenesis of the conserved aspartic acid 443, glutamic acid 478, asparagine 494, and aspartic acid 498 residues in the ribonuclease H domain of p66/p51 human immunodeficiency virus type I reverse transcriptase: expression and biochemical analysis. J. Biol. Chem. 269:19245-19249.
26. Murshudov, G. N., A. A. Vagin, and E. J. Dodson. 1997. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D Biol. Crystallogr. 53:240-255.
27. Nowotny, M., S. A. Gaidamakov, R. J. Crouch, and W. Yang. 2005. Crystal structures of RNase H bound to an RNA/DNA hybrid: substrate specificity and metal-dependent catalysis. Cell 121:1005-1016.
28. Nowotny, M., S. A. Gaidamakov, R. Ghirlando, S. M. Cerritelli, R. J. Crouch, and W. Yang. 2007. Structure of human RNase H1 complexed with an RNA/DNA hybrid: insight into HIV reverse transcription. Mol. Cell 28:264-276.
29. Nowotny, M., and W. Yang. 2006. Stepwise analyses of metal ions in RNase H catalysis from substrate destabilization to product release. EMBO J. 25:1924-1933.
30. Otwinowski, Z., and W. Minor. 1997. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276:307-326. (Pubitemid 27085611)
31. Pantoliano, M. W., E. C. Petrella, J. D. Kwasnoski, V. S. Lobanov, J. Myslik, E. Graf, T. Carver, E. Asel, B. A. Springer, P. Lane, and F. R. Salemme. 2001. High-density miniaturized thermal shift assays as a general strategy for drug discovery. J. Biomol. Screen. 6:429-440.
32. Pari, K., G. A. Mueller, E. F. DeRose, T. W. Kirby, and R. E. London. 2003. Solution structure of the RNase H domain of the HIV-1 reverse transcriptase in the presence of magnesium. Biochemistry 42:639-650. (Pubitemid 36133288)
33. Read, R. 1986. Improved Fourier coefficients for maps using phases from partial structures with errors. Acta Crystallogr. Sect. A 42:140-149.
34. Sarafianos, S. G., B. Marchand, K. Das, D. M. Himmel, M. A. Parniak, S. H. Hughes, and E. Arnold. 2009. Structure and function of HIV-1 reverse transcriptase: molecular mechanisms of polymerization and inhibition. J. Mol. Biol. 385:693-713.
35. Sluis-Cremer, N., D. Arion, and M. A. Parniak. 2002. Destabilization of the HIV-1 reverse transcriptase dimer upon interaction with N-acyl hydrazone inhibitors. Mol. Pharmacol. 62:398-405.
36. UNAIDS. 2007. AIDS epidemic update. Joint United Nations Programme on HIV/AIDS and World Health Organization, New York, NY.
37. 2+-ion catalysis and substrate specificity. Mol. Cell 22:5-13.
38. Yang, W., and T. A. Steitz. 1995. Recombining the structures of HIV integrase, RuvC and RNase H. Structure 3:131-134.
39. Zhao, Z., S. E. Wolkenberg, M. Lu, V. Munshi, G. Moyer, M. Feng, A. V. Carella, L. T. Ecto, L. J. Gabryelski, M. T. Lai, S. G. Prasad, Y. Yan, G. B. McGaughey, M. D. Miller, C. W. Lindsley, G. D. Hartman, J. P. Vacca, and T. M. Williams. 2008. Novel indole-3-sulfonamides as potent HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs). Bioorg. Med. Chem. Lett. 18:554-559.