The Folding Free-Energy Surface of HIV-1 Protease: Insights into the Thermodynamic Basis for Resistance to Inhibitors

Journal of Molecular Biology

Volumn 387, Issue 4, 2009, Pages 1002-1016

  Noel, Amanda F ^a   Bilsel, Osman ^a   Kundu, Agnita ^a   Wu, Ying ^a   Zitzewitz, Jill A ^a   Matthews, C Robert ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

dimer folding mechanisms; global analysis; jelly roll barrel motif; kinetics; thermodynamics

Indexed keywords

HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 PROTEASE; MONOMER; PROTEIN; PROTEINASE INHIBITOR; UNCLASSIFIED DRUG; UREA; VIRUS ENZYME;

ANALYSIS; ARTICLE; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DIMERIZATION; ENERGY; ENZYME MECHANISM; FLUORESCENCE; INTROSPECTION; KINETICS; MODEL; MUTATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN FOLDING; THERMODYNAMICS; WILD TYPE;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 62649160354     PISSN: 00222836     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmb.2008.12.061     Document Type: Article

References (54)

1. Barre-Sinoussi F., Chermann J.C., Rey F., Nugeyre M.T., Chamaret S., Gruest J., et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220 (1983) 868-871
2. Cohen J., and Enserink M. Nobel Prize in Physiology or Medicine. HIV, HPV researchers honored, but one scientist is left out. Science 322 (2008) 174-175
3. Kohl N.E., Emini E.A., Schleif W.A., Davis L.J., Heimbach J.C., Dixon R.A., et al. Active human immunodeficiency virus protease is required for viral infectivity. Proc. Natl Acad. Sci. USA 85 (1988) 4686-4690
4. Wlodawer A., and Erickson J.W. Structure-based inhibitors of HIV-1 protease. Annu. Rev. Biochem. 62 (1993) 543-585
5. Gulnik S., Erickson J.W., and Xie D. HIV protease: enzyme function and drug resistance. Vitam. Horm. 58 (2000) 213-256
6. Ohtaka H., Schon A., and Freire E. Multidrug resistance to HIV-1 protease inhibition requires cooperative coupling between distal mutations. Biochemistry 42 (2003) 13659-13666
7. Martin P., Vickrey J.F., Proteasa G., Jimenez Y.L., Wawrzak Z., Winters M.A., et al. "Wide-open" 1.3 Å structure of a multidrug-resistant HIV-1 protease as a drug target. Structure 13 (2005) 1887-1895
8. Kumar S., Ma B., Tsai C.J., Sinha N., and Nussinov R. Folding and binding cascades: dynamic landscapes and population shifts. Protein Sci. 9 (2000) 10-19
9. Fairlie D.P., Tyndall J.D., Reid R.C., Wong A.K., Abbenante G., Scanlon M.J., et al. Conformational selection of inhibitors and substrates by proteolytic enzymes: implications for drug design and polypeptide processing. J. Med. Chem. 43 (2000) 1271-1281
10. Piana S., Carloni P., and Parrinello M. Role of conformational fluctuations in the enzymatic reaction of HIV-1 protease. J. Mol. Biol. 319 (2002) 567-583
11. 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
12. Rick S.W., Erickson J.W., and Burt S.K. Reaction path and free energy calculations of the transition between alternate conformations of HIV-1 protease. Proteins 32 (1998) 7-16
13. Prabu-Jeyabalan M., Nalivaika E., and Schiffer C.A. How does a symmetric dimer recognize an asymmetric substrate? A substrate complex of HIV-1 protease. J. Mol. Biol. 301 (2000) 1207-1220
14. 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
15. Wlodawer A., Miller M., Jaskolski M., Sathyanarayana B.K., Baldwin E., Weber I.T., et al. Conserved folding in retroviral proteases: crystal structure of a synthetic HIV-1 protease. Science 245 (1989) 616-621
16. Ishima R., Ghirlando R., Tozser J., Gronenborn A.M., Torchia D.A., and Louis J.M. Folded monomer of HIV-1 protease. J. Biol. Chem. 276 (2001) 49110-49116
17. Ishima R., Torchia D.A., Lynch S.M., Gronenborn A.M., and Louis J.M. Solution structure of the mature HIV-1 protease monomer: insight into the tertiary fold and stability of a precursor. J. Biol. Chem. 278 (2003) 43311-43319
18. Louis J.M., Ishima R., Nesheiwat I., Pannell L.K., Lynch S.M., Torchia D.A., and Gronenborn A.M. Revisiting monomeric HIV-1 protease. Characterization and redesign for improved properties. J. Biol. Chem. 278 (2003) 6085-6092
19. Grant S.K., Deckman I.C., Culp J.S., Minnich M.D., Brooks I.S., Hensley P., et al. Use of protein unfolding studies to determine the conformational and dimeric stabilities of HIV-1 and SIV proteases. Biochemistry 31 (1992) 9491-9501
20. Darke P.L., Jordan S.P., Hall D.L., Zugay J.A., Shafer J.A., and Kuo L.C. Dissociation and association of the HIV-1 protease dimer subunits: equilibria and rates. Biochemistry 33 (1994) 98-105
21. Xie D., Gulnik S., Collins L., Gustchina E., Suvorov L., and Erickson J.W. Dissection of the pH dependence of inhibitor binding energetics for an aspartic protease: direct measurement of the protonation states of the catalytic aspartic acid residues. Biochemistry 36 (1997) 16166-16172
22. Todd M.J., Semo N., and Freire E. The structural stability of the HIV-1 protease. J. Mol. Biol. 283 (1998) 475-488
23. Panchal S.C., Bhavesh N.S., and Hosur R.V. Real time NMR monitoring of local unfolding of HIV-1 protease tethered dimer driven by autolysis. FEBS Lett. 497 (2001) 59-64
24. Panchal S.C., and Hosur R.V. Unfolding kinetics of tryptophan side chains in the dimerization and hinge regions of HIV-I protease tethered dimer by real time NMR spectroscopy. Biochem. Biophys. Res. Commun. 269 (2000) 387-392
25. Levy Y., Caflisch A., Onuchic J.N., and Wolynes P.G. The folding and dimerization of HIV-1 protease: evidence for a stable monomer from simulations. J. Mol. Biol. 340 (2004) 67-79
26. Rose J.R., Salto R., and Craik C.S. Regulation of autoproteolysis of the HIV-1 and HIV-2 proteases with engineered amino acid substitutions. J. Biol. Chem. 268 (1993) 11939-11945
27. Mildner A.M., Rothrock D.J., Leone J.W., Bannow C.A., Lull J.M., Reardon I.M., et al. The HIV-1 protease as enzyme and substrate: mutagenesis of autolysis sites and generation of a stable mutant with retained kinetic properties. Biochemistry 33 (1994) 9405-9413
28. Rose J.R., Babe L.M., and Craik C.S. Defining the level of human immunodeficiency virus type 1 (HIV-1) protease activity required for HIV-1 particle maturation and infectivity. J. Virol. 69 (1995) 2751-2758
29. Greenfield N.J. Analysis of circular dichroism data. Methods Enzymol. 383 (2004) 282-317
30. Woody R.W. Contributions of tryptophan side chains to the far-ultraviolet circular dichroism of proteins. Eur. Biophys. J. 23 (1994) 253-262
31. Henry E.R., and Hofrichter J. Singular value decomposition-application to analysis of experimental data. Methods Enzymol. 210 (1992) 129-192
32. Neet K.E., and Timm D.E. Conformational stability of dimeric proteins: quantitative studies by equilibrium denaturation. Protein Sci. 3 (1994) 2167-2174
33. Ishima R., Torchia D.A., and Louis J.M. Mutational and structural studies aimed at characterizing the monomer of HIV-1 protease and its precursor. J. Biol. Chem. 282 (2007) 17190-17199
34. Svensson A.K., Bilsel O., Kondrashkina E., Zitzewitz J.A., and Matthews C.R. Mapping the folding free energy surface for metal-free human Cu,Zn superoxide dismutase. J. Mol. Biol. 364 (2006) 1084-1102
35. Baskakov I., and Bolen D.W. Forcing thermodynamically unfolded proteins to fold. J. Biol. Chem. 273 (1998) 4831-4834
36. Qu Y., Bolen C.L., and Bolen D.W. Osmolyte-driven contraction of a random coil protein. Proc. Natl Acad. Sci. USA 95 (1998) 9268-9273
37. Myers J.K., Pace C.N., and Scholtz J.M. Denaturant m values and heat capacity changes: relation to changes in accessible surface areas of protein unfolding. Protein Sci. 4 (1995) 2138-2148
38. Bilsel O., and Matthews C.R. Barriers in protein folding reactions. Adv. Protein Chem. 53 (2000) 153-207
39. Yan M.C., Sha Y., Wang J., Xiong X.Q., Ren J.H., and Cheng M.S. Molecular dynamics simulations of HIV-1 protease monomer: assembly of N-terminus and C-terminus into beta-sheet in water solution. Proteins 70 (2008) 731-738
40. Zhang Z.Y., Poorman R.A., Maggiora L.L., Heinrikson R.L., and Kezdy F.J. Dissociative inhibition of dimeric enzymes. Kinetic characterization of the inhibition of HIV-1 protease by its COOH-terminal tetrapeptide. J. Biol. Chem. 266 (1991) 15591-15594
41. Xie D., Gulnik S., Gustchina E., Yu B., Shao W., Qoronfleh W., et al. Drug resistance mutations can effect dimer stability of HIV-1 protease at neutral pH. Protein Sci. 8 (1999) 1702-1707
42. Szeltner Z., and Polgar L. Conformational stability and catalytic activity of HIV-1 protease are both enhanced at high salt concentration. J. Biol. Chem. 271 (1996) 5458-5463
43. Tinoco I., Sauer K., Wang J.C., and Puglisi J.D. Physical Chemistry: Principles and Applications in Biological Sciences. 4th edit. (2002), Prentice Hall, Upper Saddle River, NJ
44. Fink A.L. Natively unfolded proteins. Curr. Opin. Struct. Biol. 15 (2005) 35-41
45. Uversky V.N., Oldfield C.J., and Dunker A.K. Intrinsically disordered proteins in human diseases: introducing the D2 concept. Annu. Rev. Biophys. 37 (2008) 215-246
46. Foulkes-Murzycki J.E., Scott W.R., and Schiffer C.A. Hydrophobic sliding: a possible mechanism for drug resistance in human immunodeficiency virus type 1 protease. Structure 15 (2007) 225-233
47. Rhee S.Y., Gonzales M.J., Kantor R., Betts B.J., Ravela J., and Shafer R.W. Human immunodeficiency virus reverse transcriptase and protease sequence database. Nucleic Acids Res. 31 (2003) 298-303
48. King N.M., Melnick L., Prabu-Jeyabalan M., Nalivaika E.A., Yang S.S., Gao Y., et al. Lack of synergy for inhibitors targeting a multi-drug-resistant HIV-1 protease. Protein Sci. 11 (2002) 418-429
49. Gill S.C., and von Hippel P.H. Calculation of protein extinction coefficients from amino acid sequence data. Anal. Biochem. 182 (1989) 319-326
50. Zitzewitz J.A., Bilsel O., Luo J., Jones B.E., and Matthews C.R. Probing the folding mechanism of a leucine zipper peptide by stopped-flow circular dichroism spectroscopy. Biochemistry 34 (1995) 12812-12819
51. Doyle S.M., Bilsel O., and Teschke C.M. SecA folding kinetics: a large dimeric protein rapidly forms multiple native states. J. Mol. Biol. 341 (2004) 199-214
52. Gualfetti P.J., Bilsel O., and Matthews C.R. The progressive development of structure and stability during the equilibrium folding of the alpha subunit of tryptophan synthase from Escherichia coli. Protein Sci. 8 (1999) 1623-1635
53. Matthews C.R. Effect of point mutations on the folding of globular proteins. Methods Enzymol. 154 (1987) 498-511
54. Bilsel O., Zitzewitz J.A., Bowers K.E., and Matthews C.R. Folding mechanism of the alpha-subunit of tryptophan synthase, an alpha/beta barrel protein: global analysis highlights the interconversion of multiple native, intermediate, and unfolded forms through parallel channels. Biochemistry 38 (1999) 1018-1029