Visualizing the molecular interactions of a nucleotide analog, GS-9148, with HIV-1 reverse transcriptase-DNA complex

Journal of Molecular Biology

Volumn 397, Issue 4, 2010, Pages 967-978

  Lansdon, Eric B ^a   Samuel, Dharmaraj ^a   Lagpacan, Leanna ^a   Brendza, Katherine M ^a   White, Kirsten L ^a   Hung, Magdeleine ^a   Liu, Xiaohong ^a   Boojamra, Constantine G ^a   Mackman, Richard L ^a   Cihlar, Tomas ^a   Ray, Adrian S ^a   McGrath, Mary E ^a   Swaminathan, S ^a  

^a GILEAD SCIENCES   (United States)

Author keywords

Antiretroviral therapy; Crystal structure; HIV; NRTI; Reverse transcriptase

Indexed keywords

2',3' DIDEHYDRO 2',3' DIDEOXY 2' FLUORO 5' O PHOSPHONOMETHYLADENOSINE; DEOXYADENOSINE TRIPHOSPHATE; DOUBLE STRANDED DNA; GLUTAMINE; LEUCINE; LYSINE; METHIONINE; RNA DIRECTED DNA POLYMERASE; TYROSINE;

ANTIVIRAL ACTIVITY; ANTIVIRAL RESISTANCE; ANTIVIRAL SUSCEPTIBILITY; ARTICLE; BINDING KINETICS; CONTROLLED STUDY; CRYSTAL STRUCTURE; DNA PROTEIN COMPLEX; DRUG EFFICACY; DRUG STRUCTURE; ENZYME ACTIVE SITE; ENZYME INHIBITION; ENZYME STRUCTURE; GENE MUTATION; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; NUCLEOTIDE BINDING SITE; PRIORITY JOURNAL; PROTEIN DOMAIN; STRUCTURE ACTIVITY RELATION;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 77950019614     PISSN: 00222836     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmb.2010.02.019     Document Type: Article

References (47)

1. Ray A.S. Intracellular interactions between nucleos(t)ide inhibitors of HIV reverse transcriptase. AIDS Rev. 2005, 7:113-125.
2. White A.J. Mitochondrial toxicity and HIV therapy. Sex. Transm. Infect. 2001, 77:158-173.
3. Hirsch M.S., Gunthard H.F., Schapiro J.M., Brun-Vezinet F., Clotet B., Hammer S.M., et al. Antiretroviral drug resistance testing in adult HIV-1 infection: 2008 recommendations of an International AIDS Society-USA panel. Clin. Infect. Dis. 2008, 47:266-285.
4. Wainberg M.A., Turner D. Resistance issues with new nucleoside/nucleotide backbone options. J. Acquir. Immune Defic. Syndr. 2004, 37(Suppl. 1):S36-S43.
5. Boojamra C.G., Mackman R.L., Markevitch D.Y., Prasad V., Ray A.S., Douglas J., et al. Synthesis and anti-HIV activity of GS-9148 (2′-Fd4AP), a novel nucleoside phosphonate HIV reverse transcriptase inhibitor. Bioorg. Med. Chem. Lett. 2008, 18:1120-1123.
6. Cihlar T., Ray A.S., Boojamra C.G., Zhang L., Hui H., Laflamme G., et al. Design and profiling of GS-9148, a novel nucleotide analog active against nucleoside-resistant variants of human immunodeficiency virus type 1, and its orally bioavailable phosphonoamidate prodrug, GS-9131. Antimicrob. Agents Chemother. 2008, 52:655-665.
7. Cihlar T., Laflamme G., Fisher R., Carey A.C., Vela J.E., Mackman R., Ray A.S. Novel nucleotide human immunodeficiency virus reverse transcriptase inhibitor GS-9148 with a low nephrotoxic potential: characterization of renal transport and accumulation. Antimicrob. Agents Chemother. 2009, 53:150-156.
8. Ray A.S., Vela J.E., Boojamra C.G., Zhang L., Hui H., Callebaut C., et al. Intracellular metabolism of the nucleotide prodrug GS-9131, a potent anti-human immunodeficiency virus agent. Antimicrob. Agents Chemother. 2008, 52:648-654.
9. Huang H., Chopra R., Verdine G.L., Harrison S.C. Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance. Science 1998, 282:1669-1675.
10. Sarafianos S.G., Clark A.D., Das K., Tuske S., Birktoft J.J., Ilankumaran P., et al. Structures of HIV-1 reverse transcriptase with pre- and post-translocation AZTMP-terminated DNA. EMBO J. 2002, 21:6614-6624.
11. Sarafianos S.G., Clark A.D., Tuske S., Squire C.J., Das K., Sheng D., et al. Trapping HIV-1 reverse transcriptase before and after translocation on DNA. J. Biol. Chem. 2003, 278:16280-16288.
12. Tuske S., Sarafianos S.G., Clark A.D., Ding J., Naeger L.K., White K.L., et al. Structures of HIV-1 RT-DNA complexes before and after incorporation of the anti-AIDS drug tenofovir. Nat. Struct. Mol. Biol. 2004, 11:469-474.
13. Ding J., Das K., Hsiou Y., Sarafianos S.G., Clark A.D., Jacobo-Molina A., et al. 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 Å resolution. J. Mol. Biol. 1998, 284:1095-1111.
14. Peletskaya E.N., Kogon A.A., Tuske S., Arnold E., Hughes S.H. Nonnucleoside inhibitor binding affects the interactions of the fingers subdomain of human immunodeficiency virus type 1 reverse transcriptase with DNA. J. Virol. 2004, 78:3387-3397.
15. Wing R.A., Bailey S., Steitz T.A. Insights into the replisome from the structure of a ternary complex of the DNA polymerase III alpha-subunit. J. Mol. Biol. 2008, 382:859-869.
16. Franklin M.C., Wang J., Steitz T.A. Structure of the replicating complex of a pol alpha family DNA polymerase. Cell 2001, 105:657-667.
17. Li Y., Korolev S., Waksman G. Crystal structures of open and closed forms of binary and ternary complexes of the large fragment of Thermus aquaticus DNA polymerase I: structural basis for nucleotide incorporation. EMBO J. 1998, 17:7514-7525.
18. Johnson S.J., Taylor J.S., Beese L.S. Processive DNA synthesis observed in a polymerase crystal suggests a mechanism for the prevention of frameshift mutations. Proc. Natl Acad. Sci. USA 2003, 100:3895-3900.
19. Steitz T.A. DNA- and RNA-dependent DNA polymerases. Curr. Opin. Struct. Biol. 1993, 3:31-38.
20. Steitz T.A., Smerdon S.J., Jager J., Joyce C.M. A unified polymerase mechanism for nonhomologous DNA and RNA polymerases. Science 1994, 266:2022-2025.
21. Brautigam C.A., Steitz T.A. Structural and functional insights provided by crystal structures of DNA polymerases and their substrate complexes. Curr. Opin. Struct. Biol. 1998, 8:54-63.
22. Kulkarni R., Margot N.A., Myrick F., Svarovskaia J., Chen J., Lansdon E., et al. XVIII International HIV Drug Resistance Workshop 2009, Fort Meyers, FL.
23. Doublie S., Tabor S., Long A.M., Richardson C.C., Ellenberger T. Crystal structure of a bacteriophage T7 DNA replication complex at 2.2 A resolution. Nature 1998, 391:251-258.
24. Pelletier H., Sawaya M.R., Kumar A., Wilson S.H., Kraut J. Structures of ternary complexes of rat DNA polymerase beta, a DNA template-primer, and ddCTP. Science 1994, 264:1891-1903.
25. Vaccaro J.A., Parnell K.M., Terezakis S.A., Anderson K.S. Mechanism of inhibition of the human immunodeficiency virus type 1 reverse transcriptase by d4TTP: an equivalent incorporation efficiency relative to the natural substrate dTTP. Antimicrob. Agents Chemother. 2000, 44:217-221.
26. Gao G., Orlova M., Georgiadis M.M., Hendrickson W.A., Goff S.P. Conferring RNA polymerase activity to a DNA polymerase: a single residue in reverse transcriptase controls substrate selection. Proc. Natl Acad. Sci. USA 1997, 94:407-411.
27. Menendez-Arias L. Mechanisms of resistance to nucleoside analogue inhibitors of HIV-1 reverse transcriptase. Virus Res. 2008, 134:124-146.
28. Das K., Bandwar R.P., White K.L., Feng J.Y., Sarafianos S.G., Tuske S., et al. Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. J. Biol. Chem. 2009, 284:35092-35100.
29. Boyer P.L., Sarafianos S.G., Arnold E., Hughes S.H. Nucleoside analog resistance caused by insertions in the fingers of human immunodeficiency virus type 1 reverse transcriptase involves ATP-mediated excision. J. Virol. 2002, 76:9143-9151.
30. Kohlstaedt L.A., Wang J., Friedman J.M., Rice P.A., Steitz T.A. Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 1992, 256:1783-1790.
31. Hansen J.L., Long A.M., Schultz S.C. Structure of the RNA-dependent RNA polymerase of poliovirus. Structure 1997, 5:1109-1122.
32. Delarue M., Poch O., Tordo N., Moras D., Argos P. An attempt to unify the structure of polymerases. Protein Eng. 1990, 3:461-467.
33. Poch O., Sauvaget I., Delarue M., Tordo N. Identification of four conserved motifs among the RNA-dependent polymerase encoding elements. EMBO J. 1989, 8:3867-3874.
34. Bruenn J.A. A structural and primary sequence comparison of the viral RNA-dependent RNA polymerases. Nucleic Acids Res. 2003, 31:1821-1829.
35. Dahlberg M.E., Benkovic S.J. Kinetic mechanism of DNA polymerase I (Klenow fragment): identification of a second conformational change and evaluation of the internal equilibrium constant. Biochemistry 1991, 30:4835-4843.
36. Hsieh J.C., Zinnen S., Modrich P. Kinetic mechanism of the DNA-dependent DNA polymerase activity of human immunodeficiency virus reverse transcriptase. J. Biol. Chem. 1993, 268:24607-24613.
37. Kati W.M., Johnson K.A., Jerva L.F., Anderson K.S. Mechanism and fidelity of HIV reverse transcriptase. J. Biol. Chem. 1992, 267:25988-25997.
38. Joyce C.M., Potapova O., Delucia A.M., Huang X., Basu V.P., Grindley N.D. Fingers-closing and other rapid conformational changes in DNA polymerase I (Klenow fragment) and their role in nucleotide selectivity. Biochemistry 2008, 47:6103-6116.
39. Rothwell P.J., Mitaksov V., Waksman G. Motions of the fingers subdomain of Klentaq1 are fast and not rate limiting: implications for the molecular basis of fidelity in DNA polymerases. Mol. Cell 2005, 19:345-355.
40. Rothwell P.J., Waksman G. A pre-equilibrium before nucleotide binding limits fingers subdomain closure by Klentaq1. J. Biol. Chem. 2007, 282:28884-28892.
41. Joyce C.M., Benkovic S.J. DNA polymerase fidelity: kinetics, structure, and checkpoints. Biochemistry 2004, 43:14317-14324.
42. Vande Berg B.J., Beard W.A., Wilson S.H. DNA structure and aspartate 276 influence nucleotide binding to human DNA polymerase beta. Implication for the identity of the rate-limiting conformational change. J. Biol. Chem. 2001, 276:3408-3416.
43. White K.L., Margot N.A., Ly J.K., Chen J.M., Ray A.S., Pavelko M., et al. A combination of decreased NRTI incorporation and decreased excision determines the resistance profile of HIV-1 K65R RT. AIDS 2005, 19:1751-1760.
44. Otwinowski Z.M., Minor W. Processing of X-ray diffraction data collection in oscillation mode. Methods in Enzymology 1997, vol. 276:307-326. Academic Press, New York. C.W. Carter, R.M. Sweet (Eds.).
45. Kissinger C.R., Gehlhaar D.K., Smith B.A., Bouzida D. Molecular replacement by evolutionary search. Acta Crystallogr., Sect. D: Biol. Crystallogr. 2001, 57:1474-1479.
46. Brunger A.T., Adams P.D., Clore G.M., DeLano W.L., Gros P., Grosse-Kunstleve R.W., et al. Crystallography & NMR system: a new software suite for macromolecular structure determination. Acta Crystallogr., Sect. D: Biol. Crystallogr. 1998, 54(Pt. 5):905-921.
47. Emsley P., Cowtan K. Coot: model-building tools for molecular graphics. Acta Crystallogr., Sect. D: Biol. Crystallogr. 2004, 60:2126-2132.