Inhibition of a viral enzyme by a small-molecule dimer disruptor

Nature Chemical Biology

Volumn 5, Issue 9, 2009, Pages 640-646

  Shahian, Tina ^a   Lee, Gregory M ^a   Lazic, Ana ^a   Arnold, Leggy A ^b   Velusamy, Priya ^b   Roels, Christina M ^b   Guy, R Kiplin ^b   Craik, Charles S ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBON 13; DD1 PROTEIN; DD2 PROTEIN; PROTEINASE INHIBITOR; UNCLASSIFIED DRUG; VIRUS ENZYME;

ALPHA HELIX; ARTICLE; BINDING SITE; CARBON NUCLEAR MAGNETIC RESONANCE; CONTROLLED STUDY; DIMERIZATION; DRUG CONFORMATION; DRUG POTENCY; DRUG SOLUBILITY; DRUG SYNTHESIS; ENZYME INHIBITION; GEL PERMEATION CHROMATOGRAPHY; HETERONUCLEAR SINGLE QUANTUM COHERENCE; HUMAN HERPESVIRUS 8; IC 50; MOLECULAR INTERACTION; MOLECULAR LIBRARY; MUTAGENESIS; NITROGEN NUCLEAR MAGNETIC RESONANCE; NONHUMAN; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; TITRIMETRY;

HERPESVIRIDAE; HUMAN HERPESVIRUS 8;

BINDING SITES; HERPESVIRUS 8, HUMAN; HUMANS; MODELS, MOLECULAR; POINT MUTATION; PROTEASE INHIBITORS; PROTEIN CONFORMATION; PROTEIN MULTIMERIZATION; SMALL MOLECULE LIBRARIES; SUBSTRATE SPECIFICITY;

EID: 69249156893     PISSN: 15524450     EISSN: 15524469     Source Type: Journal    
DOI: 10.1038/nchembio.192     Document Type: Article

References (50)

1. Jones, S. & Thornton, J.M. Principles of protein-protein interactions. Proc. Natl. Acad. Sci. USA 93, 13-20 (1996).
2. Hopkins, A.L. & Groom, C.R. The druggable genome. Nat. Rev. Drug Discov. 1, 727-730 (2002).
3. Lo Conte, L., Chothia, C. & Janin, J. The atomic structure of protein-protein recognition sites. J. Mol. Biol. 285, 2177-2198 (1999). (Pubitemid 29078179)
4. Berg, T. Modulation of protein-protein interactions with small organic molecules. Angew. Chem. Int. Edn. Engl. 42, 2462-2481 (2003). (Pubitemid 36753413)
5. Wells, J.A. & McClendon, C.L. Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature 450, 1001-1009 (2007).
6. Tse, C. et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 68, 3421-3428 (2008).
7. Fields, B.N. et al. Fields Virology 3177 (Lippincott Williams & Wilkins, Philadelphia, 2006).
8. Gopalsamy, A. et al. Design and syntheses of 1,6-naphthalene derivatives as selective HCMV protease inhibitors. J. Med. Chem. 47, 1893-1899 (2004).
9. Gao, M. et al. The protease of herpes simplex virus type 1 is essential for functional capsid formation and viral growth. J. Virol. 68, 3702-3712 (1994). (Pubitemid 24177395)
10. Preston, V.G., Coates, J.A. & Rixon, F.J. Identification and characterization of a herpes simplex virus gene product required for encapsidation of virus DNA. J. Virol. 45, 1056-1064 (1983).
11. Sheaffer, A.K. et al. Evidence for controlled incorporation of herpes simplex virus type 1 UL26 protease into capsids. J. Virol. 74, 6838-6848 (2000).
12. Weinheimer, S.P. et al. Autoproteolysis of herpes simplex virus type 1 protease releases an active catalytic domain found in intermediate capsid particles. J. Virol. 67, 5813-5822 (1993).
13. Welch, A.R., Woods, A.S., McNally, L.M., Cotter, R.J. & Gibson, W. A herpesvirus maturational proteinase, assemblin: identification of its gene, putative active site domain, and cleavage site. Proc. Natl. Acad. Sci. USA 88, 10792-10796 (1991). (Pubitemid 21915924)
14. Borthwick, A.D. et al. Design and synthesis of pyrrolidine-5,5-trans- lactams (5-oxohexahydropyrrolo[3,2-b]pyrroles) as novel mechanism-based inhibitors of human cytomegalovirus protease. 2. Potency and chirality. J. Med. Chem. 45, 1-18 (2002).
15. Borthwick, A.D. et al. Pyrrolidine-5,5-trans-lactams as novel mechanism-based inhibitors of human cytomegalovirus protease. Part 3: potency and plasma stability. Bioorg. Med. Chem. Lett. 12, 1719-1722 (2002).
16. Borthwick, A.D. et al. Design and synthesis of monocyclic beta-lactams as mechanism-based inhibitors of human cytomegalovirus protease. Bioorg. Med. Chem. Lett. 8, 365-370 (1998).
17. Ogilvie, W. et al. Peptidomimetic inhibitors of the human cytomegalovirus protease. J. Med. Chem. 40, 4113-4135 (1997). (Pubitemid 28008405)
18. Waxman, L. & Darke, P.L. The herpesvirus proteases as targets for antiviral chemotherapy. Antivir. Chem. Chemother. 11, 1-22 (2000). (Pubitemid 30083891)
19. Batra, R., Khayat, R. & Tong, L. Molecular mechanism for dimerization to regulate the catalytic activity of human cytomegalovirus protease. Nat. Struct. Biol. 8, 810-817 (2001). (Pubitemid 32803602)
20. Buisson, M. et al. Functional determinants of the Epstein-Barr virus protease. J. Mol. Biol. 311, 217-228 (2001). (Pubitemid 32735326)
21. Darke, P.L. et al. Active human cytomegalovirus protease is a dimer. J. Biol. Chem. 271, 7445-7449 (1996).
22. Margosiak, S.A., Vanderpool, D.L., Sisson, W., Pinko, C. & Kan, C.C. Dimerization of the human cytomegalovirus protease: kinetic and biochemical characterization of the catalytic homodimer. Biochemistry 35, 5300-5307 (1996). (Pubitemid 26129471)
23. Nomura, A.M., Marnett, A.B., Shimba, N., Dotsch, V. & Craik, C.S. Induced structure of a helical switch as a mechanism to regulate enzymatic activity. Nat. Struct. Mol. Biol. 12, 1019-1020 (2005).
24. Pray, T.R., Reiling, K.K., Demirjian, B.G. & Craik, C.S. Conformational change coupling the dimerization and activation of KSHV protease. Biochemistry 41, 1474-1482 (2002).
25. Reiling, K.K., Pray, T.R., Craik, C.S. & Stroud, R.M. Functional consequences of the Kaposi's sarcoma-associated herpesvirus protease structure: regulation of activity and dimerization by conserved structural elements. Biochemistry 39, 12796-12803 (2000).
26. Schmidt, U. & Darke, P.L. Dimerization and activation of the herpes simplex virus type 1 protease. J. Biol. Chem. 272, 7732-7735 (1997). (Pubitemid 27137326)
27. Nomura, A.M., Marnett, A.B., Shimba, N., Dotsch, V. & Craik, C.S. One functional switch mediates reversible and irreversible inactivation of a herpesvirus protease. Biochemistry 45, 3572-3579 (2006).
28. Marnett, A.B., Nomura, A.M., Shimba, N., Ortiz de Montellano, P.R. & Craik, C.S. Communication between the active sites and dimer interface of a herpesvirus protease revealed by a transition-state inhibitor. Proc. Natl. Acad. Sci. USA 101, 6870-6875 (2004). (Pubitemid 38596410)
29. Buisson, M. et al. The crystal structure of the Epstein-Barr virus protease shows rearrangement of the processed C terminus. J. Mol. Biol. 324, 89-103 (2002). (Pubitemid 35352182)
30. Qiu, X. et al. Unique fold and active site in cytomegalovirus protease. Nature 383, 275-279 (1996). (Pubitemid 26317680)
31. Qiu, X. et al. Crystal structure of varicella-zoster virus protease. Proc. Natl. Acad. Sci. USA 94, 2874-2879 (1997). (Pubitemid 27157232)
32. Shieh, H.S. et al. Three-dimensional structure of human cytomegalovirus protease. Nature 383, 279-282 (1996).
33. Tong, L. et al. A new serine-protease fold revealed by the crystal structure of human cytomegalovirus protease. Nature 383, 272-275 (1996). (Pubitemid 26317679)
34. Hoog, S.S. et al. Active site cavity of herpesvirus proteases revealed by the crystal structure of herpes simplex virus protease/inhibitor complex. Biochemistry 36, 14023-14029 (1997).
35. Pray, T.R., Nomura, A.M., Pennington, M.W. & Craik, C.S. Auto-inactivation by cleavage within the dimer interface of Kaposi's sarcoma-associated herpesvirus protease. J. Mol. Biol. 289, 197-203 (1999).
36. Shimba, N., Nomura, A.M., Marnett, A.B. & Craik, C.S. Herpesvirus protease inhibition by dimer disruption. J. Virol. 78, 6657-6665 (2004). (Pubitemid 38715961)
37. Lu, F. et al. Proteomimetic libraries: design, synthesis, and evaluation of p53-MDM2 interaction inhibitors. J. Comb. Chem. 8, 315-325 (2006). (Pubitemid 43798295)
38. Backes, B.J., Harris, J.L., Leonetti, F., Craik, C.S. & Ellman, J.A. Synthesis of positional-scanning libraries of fluorogenic peptide substrates to define the extended substrate specificity of plasmin and thrombin. Nat. Biotechnol. 18, 187-193 (2000). (Pubitemid 30091180)
39. Lazic, A., Goetz, D.H., Nomura, A.M., Marnett, A.B. & Craik, C.S. Substrate modulation of enzyme activity in the herpesvirus protease family. J. Mol. Biol. 373, 913-923 (2007). (Pubitemid 47498431)
40. Feng, B.Y. & Shoichet, B.K. A detergent-based assay for the detection of promiscuous inhibitors. Nat. Protoc. 1, 550-553 (2006).
41. Lee, G.M. & Craik, C.S. Trapping moving targets with small molecules. Science 324, 213-215 (2009).
42. Kussie, P.H. et al. Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 274, 948-953 (1996).
43. Chen, P. et al. Structure of the human cytomegalovirus protease catalytic domain reveals a novel serine protease fold and catalytic triad. Cell 86, 835-843 (1996). (Pubitemid 26303451)
44. Wu, T.D. et al. Mutation patterns and structural correlates in human immunodeficiency virus type 1 protease following different protease inhibitor treatments. J. Virol. 77, 4836-4847 (2003).
45. Hardy, J.A., Lam, J., Nguyen, J.T., O'Brien, T. & Wells, J.A. Discovery of an allosteric site in the caspases. Proc. Natl. Acad. Sci. USA 101, 12461-12466 (2004).
46. Scheer, J.M., Romanowski, M.J. & Wells, J.A. A common allosteric site and mechanism in caspases. Proc. Natl. Acad. Sci. USA 103, 7595-7600 (2006).
47. Bannwarth, L. & Reboud-Ravaux, M. An alternative strategy for inhibiting multidrug-resistant mutants of the dimeric HIV-1 protease by targeting the subunit interface. Biochem. Soc. Trans. 35, 551-554 (2007). (Pubitemid 46975073)
48. Lee, S.G. & Chmielewski, J. Rapid synthesis and in situ screening of potent HIV-1 protease dimerization inhibitors. Chem. Biol. 13, 421-426 (2006).
49. Unal, A. et al. The protease and the assembly protein of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8). J. Virol. 71, 7030-7038 (1997). (Pubitemid 27355369)
50. Brignole, E.J. & Gibson, W. Enzymatic activities of human cytomegalovirus maturational protease assemblin and its precursor (pPR, pUL80a) are comparable: [corrected] maximal activity of pPR requires self-interaction through its scaffolding domain. J. Virol. 81, 4091-4103 (2007). (Pubitemid 46847056)