Ligand-induced dimerization of Middle East Respiratory Syndrome (MERS) Coronavirus nsp5 protease (3CLpro): Implications for nsp5 regulation and the development of antivirals

Journal of Biological Chemistry

Volumn 290, Issue 32, 2015, Pages 19403-19422

  Tomar, Sakshi ^a   Johnston, Melanie L ^a   John, Sarah E St ^a   Osswald, Heather L ^a   Nyalapatla, Prasanth R ^a   Paul, Lake N ^a   Ghosh, Arun K ^a   Denison, Mark R ^b   Mesecar, Andrew D ^a  

^a PURDUE UNIVERSITY   (United States)

^b VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRAL AGENTS; CENTRIFUGATION; DIMERS; DISEASES; KINETIC THEORY; LIGANDS; VIRUSES;

ANALYTICAL ULTRACENTRIFUGATION; INHIBITOR COMPLEX; LONG RANGE INTERACTIONS; PEPTIDE SUBSTRATES; PRIMARY SEQUENCES; PROTEOLYTIC ACTIVITIES; STRUCTURAL SIMILARITY; X RAY STRUCTURAL ANALYSIS;

DIMERIZATION;

AMINO ACID; ANTIVIRUS AGENT; DIMER; LIGAND; PEPTIDOMIMETIC AGENT; PROTEIN 3CLPRO; PROTEIN NSP5; PROTEINASE; UNCLASSIFIED DRUG; 3C-LIKE PROTEASE, SARS CORONAVIRUS; CYSTEINE PROTEINASE; RECOMBINANT PROTEIN; VIRUS PROTEIN;

ARTICLE; COMPLEX FORMATION; CONCENTRATION (PARAMETERS); DIMERIZATION; DRUG DETERMINATION; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME ANALYSIS; ENZYME STRUCTURE; MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS; NONHUMAN; PRIORITY JOURNAL; PROTEIN INTERACTION; STRUCTURE ACTIVITY RELATION; ULTRACENTRIFUGATION; X RAY ANALYSIS; AMINO ACID SEQUENCE; ANTAGONISTS AND INHIBITORS; CHEMICAL PHENOMENA; CHEMISTRY; DRUG EFFECTS; ENZYME SPECIFICITY; ENZYMOLOGY; ESCHERICHIA COLI; GENE EXPRESSION; GENETICS; KINETICS; METABOLISM; MOLECULAR DOCKING; MOLECULAR GENETICS; PROTEIN MULTIMERIZATION; SEQUENCE ALIGNMENT; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

CORONAVIRUS; SARS CORONAVIRUS;

AMINO ACID SEQUENCE; ANTIVIRAL AGENTS; CRYSTALLOGRAPHY, X-RAY; CYSTEINE ENDOPEPTIDASES; ESCHERICHIA COLI; GENE EXPRESSION; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; KINETICS; LIGANDS; MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS; MOLECULAR DOCKING SIMULATION; MOLECULAR SEQUENCE DATA; PEPTIDOMIMETICS; PROTEIN MULTIMERIZATION; RECOMBINANT PROTEINS; SEQUENCE ALIGNMENT; SUBSTRATE SPECIFICITY; VIRAL PROTEINS;

EID: 84939231634     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M115.651463     Document Type: Article

References (65)

1. Alenius, S., Niskanen, R., Juntti, N., and Larsson, B. (1991) Bovine coronavirus as the causative agent of winter dysentery: serological evidence. Acta Vet. Scand. 32, 163-170
2. Barber, D. M., Nettleton, P. F., and Herring, J. A. (1985) Disease in a dairy herd associated with the introduction and spread of bovine virus diarrhoea virus. Vet. Rec. 117, 459-464
3. Perlman, S., and Netland, J. (2009) Coronaviruses post-SARS: update on replication and pathogenesis. Nat. Rev. Microbiol. 7, 439-450
4. McIntosh, K., Becker, W. B., and Chanock, R. M. (1967) Growth in suckling-mouse brain of "IBV-like" viruses from patients with upper respiratory tract disease. Proc. Natl. Acad. Sci. U.S.A. 58, 2268-2273
5. Cavallaro, J. J., and Monto, A. S. (1970) Community-wide outbreak of infection with a 229E-like coronavirus in Tecumseh, Michigan. J. Infect. Dis. 122, 272-279
6. Hamre, D., and Procknow, J. J. (1966) A new virus isolated from the human respiratory tract. Proc. Soc. Exp. Biol. Med. 121, 190-193
7. Woo, P. C., Lau, S. K., Chu, C. M., Chan, K. H., Tsoi, H. W., Huang, Y., Wong, B. H., Poon, R. W., Cai, J. J., Luk, W. K., Poon, L. L., Wong, S. S., Guan, Y., Peiris, J. S., and Yuen, K. Y. (2005) Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia. J. Virol. 79, 884-895
8. van der Hoek, L., Pyrc, K., Jebbink, M. F., Vermeulen-Oost, W., Berkhout, R. J., Wolthers, K. C., Wertheim-van Dillen, P. M., Kaandorp, J., Spaargaren, J., and Berkhout, B. (2004) Identification of a new human coronavirus. Nat. Med. 10, 368-373
9. Cui, L. J., Zhang, C., Zhang, T., Lu, R. J., Xie, Z. D., Zhang, L. L., Liu, C. Y., Zhou, W. M., Ruan, L., Ma, X. J., and Tan, W. J. (2011) Human coronaviruses HCoV-NL63 and HCoV-HKU1 in hospitalized children with acute respiratory infections in Beijing, China. Adv. Virol. 2011, 129134
10. Zaki, A. M., van Boheemen, S., Bestebroer, T. M., Osterhaus, A. D., and Fouchier, R. A. (2012) Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 367, 1814-1820
11. Butler, D. (2012) Clusters of coronavirus cases put scientists on alert. Nature 492, 166-167
12. WHO-Global Alert and Response (2014) Middle East respiratory syndrome coronavirus (MERS-CoV)-Saudi Arabia. World Health Organization, Geneva, Switzerland
13. van Boheemen, S., de Graaf, M., Lauber, C., Bestebroer, T. M., Raj, V. S., Zaki, A. M., Osterhaus, A. D., Haagmans, B. L., Gorbalenya, A. E., Snijder, E. J., and Fouchier, R. A. (2012) Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. MBio 3, e00473
14. Chan, J. F., Li, K. S., To, K. K., Cheng, V. C., Chen, H., and Yuen, K. Y. (2012) Is the discovery of the novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) the beginning of another SARS-like pandemic? J. Infect. 65, 477-489
15. Annan, A., Baldwin, H. J., Corman, V. M., Klose, S. M., Owusu, M., Nkrumah, E. E., Badu, E. K., Anti, P., Agbenyega, O., Meyer, B., Oppong, S., Sarkodie, Y. A., Kalko, E. K., Lina, P. H., Godlevska, E. V., et al. (2013) Human betacoronavirus 2c EMC/2012-related viruses in bats, Ghana and Europe. Emerg. Infect. Dis. 19, 456-459
16. Memish, Z. A., Mishra, N., Olival, K. J., Fagbo, S. F., Kapoor, V., Epstein, J. H., Alhakeem, R., Durosinloun, A., Al Asmari, M., Islam, A., Kapoor, A., Briese, T., Daszak, P., Al Rabeeah, A. A., and Lipkin, W. I. (2013) Middle East respiratory syndrome coronavirus in bats, Saudi Arabia. Emerg. Infect. Dis. 19, 1819-1823
17. Reusken, C. B., Haagmans, B. L., Müller, M. A., Gutierrez, C., Godeke, G. J., Meyer, B., Muth, D., Raj, V. S., Smits-De Vries, L., Corman, V. M., Drexler, J. F., Smits, S. L., El Tahir, Y. E., De Sousa, R., van Beek, J., et al. (2013) Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study. Lancet Infect. Dis. 13, 859-866
18. Perera, R. A., Wang, P., Gomaa, M. R., El-Shesheny, R., Kandeil, A., Bagato, O., Siu, L. Y., Shehata, M. M., Kayed, A. S., Moatasim, Y., Li, M., Poon, L. L., Guan, Y., Webby, R. J., Ali, M. A., Peiris, J. S., and Kayali, G. (2013) Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013. Euro Surveill. 18, pii=20574
19. Cauchemez, S., Van Kerkhove, M. D., Riley, S., Donnelly, C. A., Fraser, C., and Ferguson, N. M. (2013) Transmission scenarios for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and how to tell them apart. Euro Surveill. 18, 20503
20. Assiri, A., McGeer, A., Perl, T. M., Price, C. S., Al Rabeeah, A. A., Cummings, D. A., Alabdullatif, Z. N., Assad, M., Almulhim, A., Makhdoom, H., Madani, H., Alhakeem, R., Al-Tawfiq, J. A., Cotten, M., Watson, S. J., et al. (2013) Hospital outbreak of Middle East respiratory syndrome coronavirus. N. Engl. J. Med. 369, 407-416
21. Breban, R., Riou, J., and Fontanet, A. (2013) Interhuman transmissibility of Middle East respiratory syndrome coronavirus: estimation of pandemic risk. Lancet 382, 694-699
22. Cotten, M., Watson, S. J., Kellam, P., Al-Rabeeah, A. A., Makhdoom, H. Q., Assiri, A., Al-Tawfiq, J. A., Alhakeem, R. F., Madani, H., AlRabiah, F. A., Al Hajjar, S., Al-nassir, W. N., Albarrak, A., Flemban, H., Balkhy, H. H., et al. (2013) Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study. Lancet 382, 1993-2002
23. Centers for Disease Control (2014) MERS in the U.S. CDC, Atlanta, GA
24. Lu, Y., Lu, X., and Denison, M. R. (1995) Identification and characterization of a serine-like proteinase of the murine coronavirus MHV-A59. J. Virol. 69, 3554-3559
25. Lai, M. M., and Cavanagh, D. (1997) The molecular biology of coronaviruses. Adv. Virus Res. 48, 1-100
26. Ziebuhr, J., Snijder, E. J., and Gorbalenya, A. E. (2000) Virus-encoded proteinases and proteolytic processing in the Nidovirales. J. Gen. Virol. 81, 853-879
27. Anand, K., Ziebuhr, J., Wadhwani, P., Mesters, J. R., and Hilgenfeld, R. (2003) Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs. Science 300, 1763-1767
28. Yang, H., Yang, M., Ding, Y., Liu, Y., Lou, Z., Zhou, Z., Sun, L., Mo, L., Ye, S., Pang, H., Gao, G. F., Anand, K., Bartlam, M., Hilgenfeld, R., and Rao, Z. (2003) The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor. Proc. Natl. Acad. Sci. U.S.A. 100, 13190-13195
29. Yang, H., Bartlam, M., and Rao, Z. (2006) Drug design targeting the main protease, the Achilles' heel of coronaviruses. Curr. Pharm. Des. 12, 4573-4590
30. Ghosh, A. K., Xi, K., Ratia, K., Santarsiero, B. D., Fu, W., Harcourt, B. H., Rota, P. A., Baker, S. C., Johnson, M. E., and Mesecar, A. D. (2005) Design and synthesis of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease inhibitors. J. Med. Chem. 48, 6767-6771
31. Ghosh, A. K., Gong, G., Grum-Tokars, V., Mulhearn, D. C., Baker, S. C., Coughlin, M., Prabhakar, B. S., Sleeman, K., Johnson, M. E., and Mesecar, A. D. (2008) Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors. Bioorg. Med. Chem. Lett. 18, 5684-5688
32. Jacobs, J., Grum-Tokars, V., Zhou, Y., Turlington, M., Saldanha, S. A., Chase, P., Eggler, A., Dawson, E. S., Baez-Santos, Y. M., Tomar, S., Mielech, A. M., Baker, S. C., Lindsley, C. W., Hodder, P., Mesecar, A., and Stauffer, S. R. (2013) Discovery, synthesis, and structure-based optimization of a series of N-(tert-butyl)-2-(N-arylamido)-2-(pyridin-3-yl) acetamides (ML188) as potent noncovalent small molecule inhibitors of the severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL protease. J. Med. Chem. 56, 534-546
33. Turlington, M., Chun, A., Tomar, S., Eggler, A., Grum-Tokars, V., Jacobs, J., Daniels, J. S., Dawson, E., Saldanha, A., Chase, P., Baez-Santos, Y. M., Lindsley, C. W., Hodder, P., Mesecar, A. D., and Stauffer, S. R. (2013) Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: identification of ML300 and noncovalent nanomolar inhibitors with an induced-fit binding. Bioorg. Med. Chem. Lett. 23, 6172-6177
34. Hsu, M. F., Kuo, C. J., Chang, K. T., Chang, H. C., Chou, C. C., Ko, T. P., Shr, H. L., Chang, G. G., Wang, A. H., and Liang, P. H. (2005) Mechanism of the maturation process of SARS-CoV 3CL protease. J. Biol. Chem. 280, 31257-31266
35. Lai, L., Han, X., Chen, H., Wei, P., Huang, C., Liu, S., Fan, K., Zhou, L., Liu, Z., Pei, J., and Liu, Y. (2006) Quaternary structure, substrate selectivity and inhibitor design for SARS 3C-like proteinase. Curr. Pharm. Des. 12, 4555-4564
36. Chen, S., Zhang, J., Hu, T., Chen, K., Jiang, H., and Shen, X. (2008) Residues on the dimer interface of SARS coronavirus 3C-like protease: dimer stability characterization and enzyme catalytic activity analysis. J. Biochem. 143, 525-536
37. Grum-Tokars, V., Ratia, K., Begaye, A., Baker, S. C., and Mesecar, A. D. (2008) Evaluating the 3C-like protease activity of SARS-Coronavirus: recommendations for standardized assays for drug discovery. Virus Res. 133, 63-73
38. Shi, J., Sivaraman, J., and Song, J. (2008) Mechanism for controlling the dimer-monomer switch and coupling dimerization to catalysis of the severe acute respiratory syndrome coronavirus 3C-like protease. J. Virol. 82, 4620-4629
39. Chen, S., Jonas, F., Shen, C., Hilgenfeld, R., and Higenfeld, R. (2010) Liberation of SARS-CoV main protease from the viral polyprotein: N-terminal autocleavage does not depend on the mature dimerization mode. Protein Cell 1, 59-74
40. Li, C., Qi, Y., Teng, X., Yang, Z., Wei, P., Zhang, C., Tan, L., Zhou, L., Liu, Y., and Lai, L. (2010) Maturation mechanism of severe acute respiratory syndrome (SARS) coronavirus 3C-like proteinase. J. Biol. Chem. 285, 28134-28140
41. Báez-Santos, Y. M., Barraza, S. J., Wilson, M. W., Agius, M. P., Mielech, A. M., Davis, N. M., Baker, S. C., Larsen, S. D., and Mesecar, A. D. (2014) X-ray structural and biological evaluation of a series of potent and highly selective inhibitors of human coronavirus papain-like proteases. J. Med. Chem. 57, 2393-2412
42. Agnihothram, S., Yount, B. L., Jr., Donaldson, E. F., Huynh, J., Menachery, V. D., Gralinski, L. E., Graham, R. L., Becker, M. M., Tomar, S., Scobey, T. D., Osswald, H. L., Whitmore, A., Gopal, R., Ghosh, A. K., Mesecar, A., et al. (2014) A mouse model for Betacoronavirus subgroup 2c using a bat coronavirus strain HKU5 variant. MBio 5, e00047-00014
43. Ghosh, A. K., Xi, K., Grum-Tokars, V., Xu, X., Ratia, K., Fu, W., Houser, K. V., Baker, S. C., Johnson, M. E., and Mesecar, A. D. (2007) Structurebased design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors. Bioorg. Med. Chem. Lett. 17, 5876-5880
44. Shen, Y., Chou, C. Y., Chang, G. G., and Tong, L. (2006) Is dimerization required for the catalytic activity of bacterial biotin carboxylase? Mol. Cell 22, 807-818
45. Leslie, A. G., and Powell, H. R. (2007) Processing diffraction data with MOSFLM. NATO Sci. Ser. ii Math. 245, 41-51
46. Otwinowski, Z., and Minor, W. (1997) Processing of X-ray diffraction data collected in oscillation mode. Method Enzymol 276, 307-326
47. Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L. W., Kapral, G. J., Grosse-Kunstleve, R. W., Mc-Coy, A. J., Moriarty, N. W., Oeffner, R., Read, R. J., Richardson, D. C., et al. (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213-221
48. Emsley, P., Lohkamp, B., Scott, W. G., and Cowtan, K. (2010) Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486-501
49. Chen, V. B., Arendall, W. B., 3rd, Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., Murray, L. W., Richardson, J. S., and Richardson, D. C. (2010) MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr. 66, 12-21
50. DeLano, W. L. (2014) The PyMOL Molecular Graphics System, Version 1.7.2.1, Schrödinger, LLC, New York
51. Fan, K., Wei, P., Feng, Q., Chen, S., Huang, C., Ma, L., Lai, B., Pei, J., Liu, Y., Chen, J., and Lai, L. (2004) Biosynthesis, purification, and substrate specificity of severe acute respiratory syndrome coronavirus 3C-like proteinase. J. Biol. Chem. 279, 1637-1642
52. Shi, J., Wei, Z., and Song, J. (2004) Dissection study on the severe acute respiratory syndrome 3C-like protease reveals the critical role of the extra domain in dimerization of the enzyme: defining the extra domain as a new target for design of highly specific protease inhibitors. J. Biol. Chem. 279, 24765-24773
53. Blanchard, J. E., Elowe, N. H., Huitema, C., Fortin, P. D., Cechetto, J. D., Eltis, L. D., and Brown, E. D. (2004) High-throughput screening identifies inhibitors of the SARS coronavirus main proteinase. Chem. Biol. 11, 1445-1453
54. Kaeppler, U., Stiefl, N., Schiller, M., Vicik, R., Breuning, A., Schmitz, W., Rupprecht, D., Schmuck, C., Baumann, K., Ziebuhr, J., and Schirmeister, T. (2005) A new lead for nonpeptidic active-site-directed inhibitors of the severe acute respiratory syndrome coronavirus main protease discovered by a combination of screening and docking methods. J. Med. Chem. 48, 6832-6842
55. Brown, P. H., Balbo, A., and Schuck, P. (2008) Characterizing protein-protein interactions by sedimentation velocity analytical ultracentrifugation. Curr. Protoc. Immunol. Chapter 18, Unit 18.15
56. Cheng, S. C., Chang, G. G., and Chou, C. Y. (2010) Mutation of Glu-166 blocks the substrate-induced dimerization of SARS coronavirus main protease. Biophys. J. 98, 1327-1336
57. Barrila, J., Bacha, U., and Freire, E. (2006) Long-range cooperative interactions modulate dimerization in SARS 3CLpro. Biochemistry 45, 14908-14916
58. Shi, J., Han, N., Lim, L., Lua, S., Sivaraman, J., Wang, L., Mu, Y., and Song, J. (2011) Dynamically-driven inactivation of the catalytic machinery of the SARS 3C-like protease by the N214A mutation on the extra domain. PLoS Comput. Biol. 7, e1001084
59. Lim, L., Shi, J., Mu, Y., and Song, J. (2014) Dynamically-driven enhancement of the catalytic machinery of the SARS 3C-like protease by the S284-T285-I286/A mutations on the extra domain. PLoS One 9, e101941
60. Stobart, C. C., Lee, A. S., Lu, X., and Denison, M. R. (2012) Temperature-sensitive mutants and revertants in the coronavirus nonstructural protein 5 protease (3CLpro) define residues involved in long-distance communication and regulation of protease activity. J. Virol. 86, 4801-4810
61. Wu, C. G., Cheng, S. C., Chen, S. C., Li, J. Y., Fang, Y. H., Chen, Y. H., and Chou, C. Y. (2013) Mechanism for controlling the monomer-dimer conversion of SARS coronavirus main protease. Acta Crystallogr. D Biol. Crystallogr. 69, 747-755
62. Myers, D. P., Jackson, L. K., Ipe, V. G., Murphy, G. E., and Phillips, M. A. (2001) Long-range interactions in the dimer interface of ornithine decarboxylase are important for enzyme function. Biochemistry 40, 13230-13236
63. Crooks, G. E., Hon, G., Chandonia, J. M., and Brenner, S. E. (2004) WebLogo: a sequence logo generator. Genome Res. 14, 1188-1190
64. Corpet, F. (1988) Multiple sequence alignment with hierarchical clustering. Nucleic Acids Res. 16, 10881-10890
65. Robert, X., and Gouet, P. (2014) Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Res. 42, W320-W324