HIV-1 protease mutations and inhibitor modifications monitored on a series of complexes. Structural basis for the effect of the A71V mutation on the active site

Journal of Medicinal Chemistry

Volumn 49, Issue 19, 2006, Pages 5777-5784

  Skálová, Tereza ^a   Dohnálek, Jan ^a   Dušková, Jarmila ^a   Petroková, Hana ^a   Hradílek, Martin ^b   Souček, Milan ^b   Konvalinka, Jan ^b   Hašek, Jindřich ^a  

^a INSTITUTE OF MACROMOLECULAR CHEMISTRY   (Czech Republic)

^b INSTITUTE OF ORGANIC CHEMISTRY AND BIOCHEMISTRY   (Czech Republic)

Author keywords

[No Author keywords available]

Indexed keywords

ETHYLAMINE; ETHYLENE DERIVATIVE; ETHYLENEAMINE; MUTANT PROTEIN; PROTEIN OE; PROTEIN QF34; PROTEIN SE; PROTEIN SQ; PROTEINASE; PROTEINASE INHIBITOR; S HYDROXYETHYLAMINE ISOSTERE; TETRAPEPTIDE; UNCLASSIFIED DRUG;

ARTICLE; COMPLEX FORMATION; DRUG CONFORMATION; ENZYME ACTIVE SITE; ENZYME INHIBITOR COMPLEX; ENZYME MODIFICATION; GENE MUTATION; HUMAN IMMUNODEFICIENCY VIRUS 1; MOLECULAR INTERACTION; NONHUMAN; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; X RAY CRYSTALLOGRAPHY;

BINDING SITES; CRYSTALLOGRAPHY, X-RAY; ETHANOLAMINES; HIV PROTEASE; HIV PROTEASE INHIBITORS; HYDROGEN BONDING; LIGANDS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; MUTATION; OLIGOPEPTIDES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33748856573     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0605583     Document Type: Article

References (26)

1. Wlodawer, A.; Miller, A.; Jaskólski, M.; Sathyanarayana, B. K.; Baldwin, E.; Weber, I.; Selk, L. M.; Clawson, L.; Schneider, J.; Kent, S. B. H. Conserved folding in retroviral proteases: crystal structure of a synthetic HIV-1 protease. Science 1989, 245, 616-621.
2. Miller, M.; Schneider, J.; Sathyanarayana, B. K.; Toth, M. V.; Marshall, G. R.; Clawson, L.; Selk, L.; Kent, S. B. H.; Wlodawer, A. Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3-Å resolution. Science 1989, 246, 1149-1152.
3. Lapatto, R.; Blundell, T.; Hemmings, A.; Overington, J.; Wilderspin, A.; Wood, S.; Merson, J. R.; Whittle, P. J.; Danley, D. E.; Geoghegan, K. F.; Hawrylik, S. J.; Lee, S. E.; Scheld, K. G.; Hobart, P. M. X-ray analysis of HIV-1 proteinase at 2.7 Å resolution confirms structural homology among retroviral enzymes. Nature 1989, 342, 299-302.
4. Spinelli, S.; Liu, Q. Z.; Alzari, P. M.; Hirel, P. H.; Poljak, R. J. The three-dimensional structure of the aspartyl protease from the HIV-1 isolate Bru. Biochimie 1991, 73, 1391-1396.
5. Cigler, P.; Kozisek, M.; Rezacova, P.; Brynda, J.; Otwinowski, Z.; Pokorna, J.; Plesek, J.; Gruner, B.; Doleckova-Maresova, L.; Masa, M.; Sedlacek, J.; Bodem, J.; Krausslich, H. G.; Kral, V.; Konvalinka, J. From nonpeptide toward noncarbon protease inhibitors: Metallacarboranes as specific and potent inhibitors of HIV protease. Proc. Natl. Acad. Sci. U.S.A. 2005, 102 (43), 15394-15399.
6. Babine, R. E.; Bender, S. L. Molecular recognition of protein-ligand complexes: applications to drug design. Chem. Rev. 1997, 97, 1359-1472.
7. Wlodawer, A.; Vondrasek, J. Inhibitors of HIV-1 protease: A major success of structure-assisted drug design. Annu. Rev. Biophys. Biomol. Struct. 1998, 27, 249-284.
8. Rhee, S. Y.; Fessel, W. J.; Zolopa, A. R.; Hurley, L.; Liu, T.; Taylor, J.; Nguyen, D. P.; Slome, S.; Klein, D.; Horberg, M.; Flamm, J.; Follansbee, S.; Schapiro, J. M.; Shafer, R. W. J. Infect. Dis. 2005, 192, 456-465; HIV drug resistance database, http://hivdb.stanford.edu/.
9. Schock, H. B.; Garsky, V. M.; Kuo, L. C. Mutational anatomy of an HIV-1 protease variant conferring cross-resistance to protease inhibitors in clinical trials. Compensatory modulations of binding and activity. J. Biol. Chem. 1996, 271, 31957-31963.
10. Olsen, D. B.; Stahlhut, M. W.; Rutkowski, C. A.; Schock, H. B.; vanOlden, A. L.; Kuo, L. C. Non-active site changes elicit broad-based cross-resistance of the HIV-1 protease to inhibitors. J. Biol. Chem. 1999, 274, 23699-23701.
11. Munshi, S.; Chen, Z. G.; Yan, Y. W.; Li, Y.; Olsen, D. B.; Schock, H. B.; Galvin, B. B.; Dorsey, B.; Kuo, L. C. 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. 2000, 56, 381-388.
12. Konvalinka, J.; Litera, J.; Weber, J.; Vondrášek, J.; Hradílek, M.; Souček, M.; Pichová, I.; Majer, P.; Štrop, P.; Sedláček, J.; Heuser, A. M.; Kottler, H.; Kräusslich, H. G. Configurations of diastereomeric hydroxyethylene isosteres strongly affect biological activities of a series of specific inhibitors of human-immunodeficiency-virus protease. Eur. J. Biochem. 1997, 250, 559-566.
13. Dušková, J.; Dohnálek, J.; Skálová, T.; Petroková, H.; Hradílek, M.; Konvalinka, J.; Souček, M.; Brynda, J.; Fábry, M.; Sedláček, J.; Hašek, J. On the role of R-configuration of the reaction intermediate isostere in HIV-1 protease inhibitor binding; X-ray structure at 2.0 Å resolution. Acta Crystallogr., Sect. D: Biol. Crystallogr. 2006, 62, 489-497.
14. Dohnalek, J.; Hasek, J.; Duskova, J.; Petrokova, H.; Hradilek, M.; Soucek, M.; Konvalinka, J.; Brynda, J.; Sedlacek, J.; Fabry, M. Hydroxyethylamine isostere of an HIV-1 protease inhibitor prefers its amine to the hydroxy group in binding to catalytic aspartates. A synchrotron study of HIV-1 protease in complex with a peptidomimetic inhibitor. J. Med. Chem. 2002, 45, 1432-1438.
15. Petrokova, H.; Duskova, J.; Dohnalek, J.; Skalova, T.; Vondrackova-Buchtelova, E.; Soucek, M.; Konvalinka, J.; Brynda, J.; Fabry, M.; Sedlacek, J.; Hasek, J. Role of hydroxyl group and R/S configuration of isostere in binding properties of HIV-1 protease inhibitors. Eur. J. Biochem. 2004, 271, 4451-4461.
16. Skalova, T.; Hasek, J.; Dohnalek, J.; Petrokova, H.; Buchtelova, E.; Duskova, J.; Soucek, M.; Majer, P.; Uhlikova, T.; Konvalinka, J. An ethylenamine inhibitor binds tightly to both wild type and mutant HIV-1 proteases. Structure and energy study. J. Med. Chem. 2003, 46, 1636-1644.
17. Weber, J.; Mesters, J. R.; Lepsik, M.; Prejdova, J.; Svec, M.; Sponarova, J.; Mlcochova, P.; Skalicka, K.; Strisovsky, K.; Uhlikova, T.; Soucek, M.; Machala, L.; Stankova, M.; Vondrasek, J.; Klimkait, T.; Kraeusslich, H. G.; Hilgenfeld, R.; Konvalinka, J. Unusual binding mode of an HIV-1 protease inhibitor explains its potency against multi-drug-resistant virus strains. J. Mol. Biol. 2002, 324, 739-754.
18. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The Protein Data Bank. Nucleic Acids Res. 2000, 28, 235-242.
19. Babine, R. E.; Bender, S. L. Molecular recognition of protein-ligand complexes: Applications to drug design. Chem. Rev. 1997, 97, 1359-1472.
20. InsightII; Molecular Simulations, Inc.: San Diego, CA, 2000.
21. Cleland, W. W.; Perry, A. F.; Gerlt, J. A. The low barrier hydrogen bond in enzymatic catalysis. J. Biol. Chem. 1998, 273, 25529-25532.
22. Priestle, J. P.; Fässler, A.; Rosel, J.; Tinelnot-Blomley, M.; Strop, P.; Grütter, M. G. Comparative analysis of the X-ray structures of HIV-1 and HIV-2 proteases in complex with CGP 53820, a novel pseudosymmetric inhibitor. Structure 1995, 15, 381-389.
23. Skalova, T. HIV-1 Protease and Its Interaction with Inhibitors. Ph.D. Thesis, Faculty of Mathematics and Physics, Charles University, Prague, Czech Republic, 2003.
24. Dohnalek, J.; Hasek, J.; Duskova, J.; Petrokova, H.; Hradilek, M.; Soucek, M.; Konvalinka, J.; Brynda, J.; Sedlacek, J.; Fabry, M. A distinct binding mode of a hydroxyethylamine isostere inhibitor of HIV-1 protease. Acta Crystallogr., Sect. D: Biol. Crystallogr. 2001, 57, 472-476.
25. Brunger, A. T.; Adams, P. D.; Clore, G. M.; DeLano, W. L.; Gros, P.; Grosse-Kunstleve, R. W.; Jiang, J. S.; Kuszewski, J.; Nilges, M.; Pannu, N. S.; et al. Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr., Sect. D: Biol. Crystallogr. 1998, 54, 905-921.
26. DeLano, W. L. The PyMOL Molecular Graphics System (2002). http://www.pymol.org.