Effect of Flap Mutations on Structure of HIV-1 Protease and Inhibition by Saquinavir and Darunavir

Journal of Molecular Biology

Volumn 381, Issue 1, 2008, Pages 102-115

  Liu, Fengling ^a   Kovalevsky, Andrey Y ^a   Tie, Yunfeng ^a   Ghosh, Arun K ^b   Harrison, Robert W ^a   Weber, Irene T ^a  

^a GEORGIA STATE UNIVERSITY   (United States)

^b PURDUE UNIVERSITY   (United States)

Author keywords

aspartic protease; darunavir (TMC114); drug resistance; saquinavir

Indexed keywords

ARACHIDONATE 5 LIPOXYGENASE ACTIVATING PROTEIN; DARUNAVIR; GLYCINE; ISOLEUCINE; PROTEINASE; SAQUINAVIR;

ARTICLE; CONFORMATION; CONTROLLED STUDY; CRYSTAL STRUCTURE; ENZYME INHIBITION; ENZYME STRUCTURE; HUMAN IMMUNODEFICIENCY VIRUS 1; KINETICS; MUTANT; MUTATION; NONHUMAN; PRIORITY JOURNAL; WILD TYPE;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 46649092697     PISSN: 00222836     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmb.2008.05.062     Document Type: Article

References (47)

1. Miller M., Schneider J., Sathyanarayana B.K., Toth M.V., Marshall G.R., Clawson L., et al. Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 Å resolution. Science 246 (1989) 1149-1152
2. Gustchina A., and Weber I.T. Comparison of inhibitor binding in HIV-1 protease and in non-viral aspartic proteases: the role of the flap. FEBS Lett. 269 (1990) 269-272
3. Ishima R., Freedberg D.I., Wang Y.-X., Louis J.M., and Torchia D.A. Flap opening and dimer-interface flexibility in the free and inhibitor-bound HIV protease. Structure 7 (1999) 1047-1055
4. Shao W., Everitt L., Manchester M., Loeb D.D., Hutchison III C.A., and Swanstrom R. Sequence requirements of the HIV-1 protease flap region determined by saturation mutagenesis and kinetic analysis of flap mutants. Proc. Natl Acad. Sci. USA 94 (1997) 2243-2248
5. Shafer R.W. Genotypic testing for human immunodeficiency virus type 1 drug resistance. Clin. Microbiol. Rev. 15 (2002) 247-277
6. Shafer R.W., Rhee S.Y., Pillay D., Miller V., Sandstrom P., Schapiro J.M., et al. HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance. AIDS 21 (2007) 215-223
7. Heaslet H., Rosenfeld R., Giffin M., Lin Y.C., Tam K., Torbett B.E., et al. Conformational flexibility in the flap domains of ligand-free HIV protease. Acta Crystallogr., Sect. D: Biol. Crystallogr. 63 (2007) 866-875
8. Liu F., Kovalevsky A.Y., Louis J.M., Boross P.I., Wang Y.F., Harrison R.W., and Weber I.T. Mechanism of drug resistance revealed by the crystal structure of the unliganded HIV-1 protease with F53L mutation. J. Mol. Biol. 358 (2006) 1191-1199
9. Logsdon B.C., Vickrey J.F., Martin P., Proteasa G., Koepke J.I., Terlecky S.R., et al. Crystal structures of a multidrug-resistant human immunodeficiency virus type 1 protease reveal an expanded active-site cavity. J. Virol. 78 (2004) 3123-3132
10. Prabu-Jeyabalan M., Nalivaika E.A., Romano K., and Schiffer C.A. Mechanism of substrate recognition by drug-resistant human immunodeficiency virus type 1 protease variants revealed by a novel structural intermediate. J. Virol. 80 (2006) 3607-3616
11. Kovalevsky A.Y., Tie Y., Liu F., Boross P.I., Wang Y.F., Leshchenko S., et al. Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90M. J. Med. Chem. 49 (2006) 1379-1387
12. Kovalevsky A.Y., Liu F., Leshchenko S., Ghosh A.K., Louis J.M., Harrison R.W., and Weber I.T. Ultra-high resolution crystal structure of HIV-1 protease mutant reveals two binding sites for clinical inhibitor TMC114. J. Mol. Biol. 363 (2006) 161-173
13. Liu F., Boross P.I., Wang Y.F., Tozser J., Louis J.M., Harrison R.W., and Weber I.T. Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S. J. Mol. Biol. 354 (2005) 789-800
14. Mahalingam B., Louis J.M., Reed C.C., Adomat J.M., Krouse J., Wang Y.F., et al. Structural and kinetic analysis of drug resistant mutants of HIV-1 protease. Eur. J. Biochem. 263 (1999) 238-245
15. Wang Y.F., Tie Y., Boross P.I., Tozser J., Ghosh A.K., Harrison R.W., and Weber I.T. Potent new antiviral compound shows similar inhibition and structural interactions with drug resistant mutants and wild type HIV-1 protease. J. Med. Chem. 50 (2007) 4509-4515
16. Buonaguro L., Tornesello M.L., and Buonaguro F.M. Human immunodeficiency virus type 1 subtype distribution in the worldwide epidemic: pathogenetic and therapeutic implications. J. Virol. 81 (2007) 10209-10219
17. Coman R.M., Robbins A.H., Fernandez M.A., Gilliland C.T., Sochet A.A., Goodenow M.M., et al. The contribution of naturally occurring polymorphisms in altering the biochemical and structural characteristics of HIV-1 subtype C protease. Biochemistry 47 (2008) 731-743
18. Sanches M., Krauchenco S., Martins N.H., Gustchina A., Wlodawer A., and Polikarpov I. Structural characterization of B and non-B subtypes of HIV-protease: insights into the natural susceptibility to drug resistance development. J. Mol. Biol. 369 (2007) 1029-1040
19. De Meyer S., Azijn H., Surleraux D., Jochmans D., Tahri A., Pauwels R., et al. TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. Antimicrob. Agents Chemother. 49 (2005) 2314-2321
20. Koh Y., Nakata H., Maeda K., Ogata H., Bilcer G., Devasamudram T., et al. A novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI) UIC-94017 (TMC114) potent against multi-PI-resistant HIV in vitro. Antimicrob. Agents Chemother. 47 (2003) 3123-3129
21. Tie Y., Boross P.I., Wang Y.F., Gaddis L., Hussain A.K., Leshchenko S., et al. High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains. J. Mol. Biol. 338 (2004) 341-352
22. Tie, Y., Kovalevsky, A. Y., Boross, P. I., Wang, Y. F., Ghosh, A. K., Tozser, J. et al. (in press). High resolution crystal structures of HIV-1 protease and mutants V82A and I84V with saquinavir. Proteins: Struct., Funct., Bioinf. 67, 232-242.
23. Ghosh A.K., Dawson Z.L., and Mitsuya H. Darunavir, a conceptually new HIV-1 protease inhibitor for the treatment of drug-resistant HIV. Bioorg. Med. Chem. 15 (2007) 7576-7580
24. Noble S., and Foulds D. Saquinavir: a review of its pharmacology and clinical potential in the management of HIV infection. Drugs 52 (1996) 93-112
25. Shapiro J.M., Winters M.A., Lawrence J., and Merigan T.C. Clinical cross-resistance between the HIV-1 protease inhibitors saquinavir and indinavir and correlations with genotypic mutations. AIDS 13 (1999) 359-365
26. Condra J.H., Petropoulos C.J., Ziermann R., Schleif W.A., Shivaprakash M., and Emini E.A. Drug resistance and predicted virologic responses to human immunodeficiency virus type 1 protease inhibitor therapy. J. Infect. Dis. 182 (2000) 758-765
27. Molla A., Korneyeva M., Gao Q., Vasavanonda S., Schipper P.J., Mo H.M., et al. Ordered accumulation of mutations in HIV protease confers resistance to ritonavir. Nat. Med. 2 (1996) 760-766
28. Murphy M.D., Marousek G.I., and Chou S. HIV protease mutations associated with amprenavir resistance during salvage therapy: importance of I54M. J. Clin. Virol. 30 (2004) 62-67
29. Lambert-Niclot S., Flandre P., Canestri A., Peytavin G., Blanc C., Agher R., et al. Factors associated with the selection of mutations conferring resistance to protease inhibitors (PIs) in PI-experienced patients displaying treatment failure on darunavir. Antimicrob. Agents Chemother. 52 (2008) 491-496
30. Hong L., Zhang X.C., Hartsuck J.A., and Tang J. Crystal structure of an in vivo HIV-1 protease mutant in complex with saquinavir: insights into the mechanisms of drug resistance. Protein Sci. 9 (2000) 1898-1904
31. Louis J.M., Clore G.M., and Gronenborn A.M. Autoprocessing of HIV-1 protease is tightly coupled to protein folding. Nat. Struct. Biol. 6 (1999) 868-875
32. Zoete V., Michielin O., and Karplus M. Relation between sequence and structure of HIV-1 protease inhibitor complexes: a model system for the analysis of protein flexibility. J. Mol. Biol. 315 (2002) 21-52
33. Weber I.T., Kovalevsky A.Y., and Harrison R.W. Structures of HIV protease guide inhibitor design to overcome drug resistance. In: Caldwell G.W., Atta-ur-Rahman, Player M.R., and Choudhary M.I. (Eds). Frontiers in Drug Design and Discovery vol. 3 (2007), Bentham Science Publishers, Sharjah, UAR; Bussum, The Netherlands; OakPark, IL, USA; Karachi, Pakistan 45-62
34. Munshi S., Chen Z., Yan Y., Li Y., Olsen D.B., Schock H.B., et al. An alternate binding site for the P1-P3 group of a class of potent HIV-1 protease inhibitors as a result of concerted structural change in the 80s loop of the protease. Acta Crystallogr., Sect. D: Biol. Crystallogr. 56 (2000) 381-388
35. Tie Y., Boross P.I., Wang Y.F., Gaddis L., Liu F., Chen X., et al. Molecular basis for substrate recognition and drug resistance from 1.1 to 1.6 angstroms resolution crystal structures of HIV-1 protease mutants with substrate analogs. FEBS J. 272 (2005) 5265-5277
36. Foulkes J.E., Prabu-Jeyabalan M., Cooper D., Henderson G.J., Harris J., Swanstrom R., and Schiffer C.A. Role of invariant Thr80 in human immunodeficiency virus type 1 protease structure, function, and viral infectivity. J. Virol. 80 (2006) 6906-6916
37. Kovalevsky A.Y., Chumanevich A.A., Liu F., Louis J.M., and Weber I.T. Caught in the act: the 1.5 Å resolution crystal structures of the HIV-1 protease and the I54V mutant reveal a tetrahedral reaction intermediate. Biochemistry 46 (2007) 14854-14864
38. Mahalingam B., Louis J.M., Hung J., Harrison R.W., and Weber I.T. Structural implications of drug-resistant mutants of HIV-1 protease: high-resolution crystal structures of the mutant protease/substrate analogue complexes. Proteins: Struct., Funct., Genet. 43 (2001) 455-464
39. Maibaum J., and Rich D.H. Inhibition of porcine pepsin by two substrate analogues containing statine. The effect of histidine at the P2 subsite on the inhibition of aspartic proteinases. J. Med. Chem. 31 (1988) 625-629
40. Otwinowski Z., and Minor W. Processing of X-ray diffraction data in oscillation mode. Methods Enzymol. 276 (1997) 307-326
41. Collaborative Computational Project No. 4. The CCP4 Suite: programs for protein crystallography. Acta Crystallogr., Sect. D: Biol. Crystallogr. 50 (1994) 760-763
42. Potterton E., Briggs P., Turkenburg M., and Dodson E.A. Graphical user interface to the CCP4 program suite. Acta Crystallogr., Sect. D: Biol. Crystallogr. 59 (2003) 1131-1137
43. Sheldrick G.M., and Schneider T.R. SHELXL: high-resolution refinement. Methods Enzymol. 277 (1997) 319-343
44. Jones T.A., Zou J.Y., Cowan S.W., and Kjeldgaard M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr., Sect. A: Found. Crystallogr. 47 (1991) 110-119
45. Esnouf R.M. An extensively modified version of MolScript that includes greatly enhanced coloring capabilities. J. Mol. Graphics Modell. 15 (1997) 132-134
46. Esnouf R.M. Further additions to MolScript version 1.4, including reading and contouring of electron-density maps. Acta Crystallogr., Sect. D: Biol. Crystallogr. 55 (1999) 938-940
47. DeLano, W. L. (2002). The PyMOL Molecular Graphics System. http://www.pymol.org.