Probing nonnucleoside inhibitor-induced active-site distortion in HIV-1 reverse transcriptase by transient kinetic analyses

Protein Science

Volumn 16, Issue 8, 2007, Pages 1728-1737

  Xia, Qing ^a   Radzio, Jessica ^a   Anderson, Karen S ^b   Sluis Cremer, Nicolas ^a  

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

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

HIV; Nonnucleoside reverse transcriptase inhibitor; Phosphorothioate metal effect; Presteady state kinetics; Reverse transcriptase

Indexed keywords

DELAVIRDINE; EFAVIRENZ; NEVIRAPINE; PHOSPHODIESTERASE; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR;

ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DIMERIZATION; DNA SYNTHESIS; ENZYME ACTIVE SITE; ENZYME ASSAY; ENZYME INHIBITION; HUMAN IMMUNODEFICIENCY VIRUS 1; KINETICS; NONHUMAN; POLYMERIZATION; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN STRUCTURE; RNA PROBE;

ANTI-HIV AGENTS; BENZOXAZINES; BINDING SITES; CATALYSIS; DELAVIRDINE; HIV-1 REVERSE TRANSCRIPTASE; KINETICS; MODELS, MOLECULAR; NEVIRAPINE; PROTEIN CONFORMATION; REVERSE TRANSCRIPTASE INHIBITORS; THYMINE NUCLEOTIDES;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 34547578940     PISSN: 09618368     EISSN: 1469896X     Source Type: Journal    
DOI: 10.1110/ps.072829007     Document Type: Article

References (37)

1. Camarasa, M.J., San-Felix, A., Velazquez, S., Perez-Perez, M.J., Gago, F., and Balzarini, J. 2004. TSAO compounds: The comprehensive story of a unique family of HIV-1 specific inhibitors of reverse transcriptase. Curr. Top. Med. Chem. 4: 945-963.
2. Choi, J.Y. and Guengerich, F.P. 2004. Analysis of the effect of bulk at N2-alkylguanine DNA adducts on catalytic efficiency and fidelity of the processive DNA polymerases bacteriophage T7 exonuclease- and HIV-1 reverse transcriptase. J. Biol. Chem. 279: 19217-19229.
3. Ding, J., Das, K., Moereels, H., Koymans, L., Andries, K., Janssen, P.A., Hughes, S.H., and Arnold, E. 1995. Structure of HIV-1 RT/TIBO R 86183 complex reveals similarity in the binding of diverse nonnucleoside inhibitors. Nat. Struct. Biol. 2: 407-415.
4. Ding, J., Das, K., Hsiou, Y., Sarafianos, S.G., Clark Jr., A.D., Jacobo-Molina, A., Tantillo, C., Hughes, S.H., and Arnold, E. 1998. Structure and functional implications of the polymerase active site region in a complex of HIV-1 RT with a double-stranded DNA template-primer and an antibody Fab fragment at 2.8 A resolution. J. Mol. Biol. 284: 1095-1111.
5. Esnouf, R., Ren, J., Ross, C., Jones, Y., Stammers, D., and Stuart, D. 1995. Mechanism of inhibition of HIV-1 reverse transcriptase by nonnucleoside inhibitors. Nat. Struct. Biol. 2: 303-308.
6. Esnouf, R.M., Ren, J., Hopkins, A.L., Ross, C.K., Jones, E.Y., Stammers, D.K., and Stuart, D.I. 1997. Unique features in the structure of the complex between HIV-1 reverse transcriptase and the bis(heteroaryl)piperazine (BHAP) U-90152 explain resistance mutations for this nonnucleoside inhibitor. Proc. Natl. Acad. Sci. 94: 3984-3989.
7. Figueiredo, A., Moore, K.L., Mak, J., Sluis-Cremer, N., de Bethune, M.P., and Tachedjian, G. 2006. Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 Gag-Pol. PLoS Pathog. 2: e119. doi: 10.1371/journal.ppat.0020119.
8. Hsieh, J.C., Zinnen, S., and Modrich, P. 1993. Kinetic mechanism of the DNA-dependent DNA polymerase activity of human immunodeficiency virus reverse transcriptase. J. Biol. Chem. 268: 24607-24613.
9. Hsiou, Y., Ding, J., Das, K., Clark Jr., A.D., Hughes, S.H., and Arnold, E. 1996. Structure of unliganded HIV-1 reverse transcriptase at 2.7 A resolution: Implications of conformational changes for polymerization and inhibition mechanisms. Structure 4: 853-860.
10. 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.
11. Jochmans, D., Deval, J., Kesteleyn, B., Van Marck, H., Bettens, E., De Baere, I., Dehertogh, P., Ivens, T., Van Ginderen, M., Van Schoubroeck, B., et al. 2006. Indolopyridones inhibit human immunodeficiency virus reverse transcriptase with a novel mechanism of action. J. Virol. 80: 12283-12292.
12. Kohlstaedt, L.A., Wang, J., Friedman, J.M., Rice, P.A., and Steitz, T.A. 1992. Crystal structure at 3.5 Å resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 256: 1783-1790.
13. Kuchta, R.D., Mizrahi, V., Benkovic, P.A., Johnson, K.A., and Benkovic, S.J. 1987. Kinetic mechanism of DNA polymerase I (Klenow). Biochemistry 26: 8410-8417.
14. 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.
15. Parniak, M.A. and Sluis-Cremer, N. 2000. Inhibitors of HIV-1 reverse transcriptase. Adv. Pharmacol. 49: 67-109.
16. Pata, J.D., Stirtan, W.G., Goldstein, S.W., and Steitz, T.A. 2004. Structure of HIV-1 reverse transcriptase bound to an inhibitor active against mutant reverse transcriptases resistant to other nonnucleoside inhibitors. Proc. Natl. Acad. Sci. 101: 10548-10553.
17. Patel, S.S., Wong, I., and Johnson, K.A. 1991. Pre-steady-state kinetic analysis of processive DNA replication including complete characterization of an exonuclease-deficient mutant. Biochemistry 30: 511-525.
18. Radzio, J. and Sluis-Cremer, N. 2005. Stereo-selectivity of HIV-1 reverse transcriptase toward isomers of thymidine-5′-O-1-thiotriphosphate. Protein Sci. 14: 1929-1933.
19. Ray, A.S., Murakami, E., Basavapathruni, A., Vaccaro, J.A., Ulrich, D., Chu, C.K., Schinazi, R.F., and Anderson, K.S. 2003. Probing the molecular mechanisms of AZT drug resistance mediated by HIV-1 reverse transcriptase using a transient kinetic analysis. Biochemistry 42: 8831-8841.
20. Reardon, J.E. 1992. Human immunodeficiency virus reverse transcriptase: Steady-state and pre-steady-state kinetics of nucleotide incorporation. Biochemistry 31: 4473-4479.
21. Ren, J., Milton, J., Weaver, K.L., Short, S.A., Stuart, D.I., and Stammers, D.K. 2000. Structural basis for the resilience of efavirenz (DMP-266) to drug resistance mutations in HIV-1 reverse transcriptase. Struct. Fold. Des. 8: 1089-1094.
22. Rittinger, K., Divita, G., and Goody, R.S. 1995. Human immunodeficiency virus reverse transcriptase substrate-induced conformational changes and the mechanism of inhibition by nonnucleoside inhibitors. Proc. Natl. Acad. Sci. 92: 8046-8049.
23. Shan, S.O. and Herschlag, D. 2002. Dissection of a metal-ion-mediated conformational change in Tetrahymena ribozyme catalysis. RNA 8: 861-872.
24. Sluis-Cremer, N. and Tachedjian, G. 2002. Modulation of the oligomeric structures of HIV-1 retroviral enzymes by synthetic peptides and small molecules. Eur. J. Biochem. 269: 5103-5111.
25. Sluis-Cremer, N., Temiz, N.A., and Bahar, I. 2004. Conformational changes in HIV-1 reverse transcriptase induced by nonnucleoside reverse transcriptase inhibitor binding. Curr HIV Res. 2: 323-332.
26. Spence, R.A., Kati, W.M., Anderson, K.S., and Johnson, K.A. 1995. Mechanism of inhibition of HIV-1 reverse transcriptase by nonnucleoside inhibitors. Science 267: 988-993.
27. Spence, R.A., Anderson, K.S., and Johnson, K.A. 1996. HIV-1 reverse transcriptase resistance to nonnucleoside inhibitors. Biochemistry 35: 1054-1063.
28. Tachedjian, G. and Goff, S.P. 2003. The effect of NNRTIs on HIV reverse transcriptase dimerization. Curr. Opin. Investig. Drugs 4: 966-973.
29. Tachedjian, G., Orlova, M., Sarafianos, S.G., Arnold, E., and Goff, S.P. 2001. Nonnucleoside reverse transcriptase inhibitors are chemical enhancers of dimerization of the HIV type 1 reverse transcriptase. Proc. Natl. Acad. Sci. 98: 7188-7193.
30. Tachedjian, G., Moore, K.L., Goff, S.P., and Sluis-Cremer, N. 2005a. Efavirenz enhances the proteolytic processing of an HIV-1 pol polyprotein precursor and reverse transcriptase homodimer formation. FEBS Lett. 579: 379-384.
31. Tachedjian, G., Radzio, J., and Sluis-Cremer, N. 2005b. Relationship between enzyme activity and dimeric structure of recombinant HIV-1 reverse transcriptase. Proteins 60: 5-13.
32. Wang, L.Z., Kenyon, G.L., and Johnson, K.A. 2004. Novel mechanism of inhibition of HIV-1 reverse transcriptase by a new non-nucleoside analog, KM-1. J. Biol. Chem. 279: 38424-38432.
33. Woodside, A.M. and Guengerich, F.P. 2002. Misincorporation and stalling at O(6)-methylguanine and O(6)-benzylguanine: Evidence for inactive polymerase complexes. Biochemistry 41: 1039-1050.
34. Young, S.D., Britcher, S.F., Tran, L.O., Payne, L.S., Lumma, W.C., Lyle, T.A., Huff, J.R., Anderson, P.S., Olsen, D.B., Carroll, S.S., et al. 1995. L-743, 726 (DMP-266): A novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type 1 reverse transcriptase. Antimicrob. Agents Chemother. 39: 2602-2605.
35. Zakharova, E., Wang, J., and Konigsberg, W. 2004. The activity of selected RB69 DNA polymerase mutants can be restored by manganese ions: The existence of alternative metal ion ligands used during the polymerization cycle. Biochemistry 43: 6587-6595.
36. Zang, H., Harris, T.M., and Guengerich, F.P. 2005. Kinetics of nucleotide incorporation opposite polycyclic aromatic hydrocarbon-DNA adducts by processive bacteriophage T7 DNA polymerase. Chem. Res. Toxicol. 18: 389-400.
37. Zinnen, S., Hsieh, J.C., and Modrich, P. 1994. Misincorporation and mispaired primer extension by human immunodeficiency virus reverse transcriptase. J. Biol. Chem. 269: 24195-24202.