Analysis of the structure-activity relationship of four herpesviral UL97 subfamily protein kinases reveals partial but not full functional conservation

Journal of Medicinal Chemistry

Volumn 49, Issue 24, 2006, Pages 7044-7053

  Romaker, Daniel ^a,b   Schregel, Vera ^a   Maurer, Katja ^a   Auerochs, Sabrina ^a   Marzi, Andrea ^a   Sticht, Heinrich ^a   Marschall, Manfred ^a  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^b UNIVERSITY OF FREIBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; AMINO ACID; PROTEIN KINASE; PROTEIN KINASE INHIBITOR;

AMINO ACID SEQUENCE; ARTICLE; BINDING SITE; CATALYSIS; CONTROLLED STUDY; CYTOMEGALOVIRUS; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; ENZYME SPECIFICITY; ENZYME STRUCTURE; EPSTEIN BARR VIRUS; GENETIC COMPLEMENTATION; GENETIC CONSERVATION; HERPES SIMPLEX VIRUS; HERPES VIRUS; HUMAN; HUMAN CELL; HUMAN CYTOMEGALOVIRUS; MOLECULAR RECOGNITION; NONHUMAN; PROTEIN EXPRESSION; SEQUENCE HOMOLOGY; STRUCTURE ACTIVITY RELATION; VIRUS MUTANT; VIRUS REPLICATION;

ADENOSINE TRIPHOSPHATE; AMINO ACID SEQUENCE; ANIMALS; BINDING SITES; CATALYTIC DOMAIN; CELL LINE; CONSERVED SEQUENCE; CYTOMEGALOVIRUS; HERPESVIRIDAE; HERPESVIRUS 4, HUMAN; HUMANS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTATION; PHOSPHORYLATION; PHOSPHOTRANSFERASES (ALCOHOL GROUP ACCEPTOR); PROTEIN CONFORMATION; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; PROTEIN-SERINE-THREONINE KINASES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; VIRAL PROTEINS; VIRUS REPLICATION;

EID: 33845366594     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm060696s     Document Type: Article

References (50)

1. Marschall, M.; Freitag, M.; Suchy, P.; Romaker, D.; Kupfer, R.; Hanke, M.; Stamminger, T. The protein kinase pUL97 of human cytomegalovirus interacts with and phosphorylates the DNA polymerase processivity factor pUL44. Virology 2003, 311, 60-71.
2. Wolf, D. G.; Courcelle, C. T.; Prichard, M. N.; Mocarski, E. S. Distinct and separate roles for herpesvirus-conserved UL97 kinase in cytomegalovirus DNA synthesis and encapsidation. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 1895-1900.
3. Biron, K. K.; Harvey, R. J.; Chamberlain, S. C.; Good, S. S.; Smith, A. A., III; Davis, M. G.; Talarico, C. L.; Miller, W. H.; Ferris, R.; Dornsife, R. E.; Stanat, S. C.; Drach, J. C.; Townsend, L. B.; Koszalka, G. W. Potent and selective inhibition of human cytomegalovirus replication by 1263W94, a benzimidazole L-riboside with a unique mode of action. Antimicrob. Agents Chemother. 2002, 46, 2365-2372.
4. Baek, M. C.; Krosky, P. M.; Pearson, A.; Coen, D. M. Phosphorylation of the RNA polymerase II carboxyl-terminal domain in human cytomegalovirus-infected cells and in vitro by the viral UL97 protein kinase. Virology 2004, 324, 184-193.
5. Kawaguchi, Y.; Matsumura, T.; Roizman, B.; Hirai, K. Cellular elongation factor 1δ is modified in cells infected with representative alpha-, beta-, or gammaherpesviruses. J. Virol. 1999, 73, 4456-4460.
6. Krosky, P. M.; Baek, M. C.; Coen, D. M. The human cytomegalovirus UL97 protein kinase, an antiviral drug target, is required at the stage of nuclear egress. J. Virol. 2003, 77, 905-914.
7. Marschall, M.; Marzi, A.; aus dem Siepen, P.; Jochmann, R.; Kalmer, M.; Auerochs, S.; Lischka, P.; Leis, M.; Stamminger, T. Cellular p32 recruits cytomegalovirus kinase pUL97 to redistribute the nuclear lamina. J. Biol. Chem. 2005, 280, 33357-33367.
8. Kawaguchi, Y.; Kato, K. Protein kinases conserved in herpesviruses potentially share a function mimicking the cellular protein kinase cdc2. Rev. Med. Virol. 2003, 13, 331-340.
9. Marschall, M.; Stein-Gerlach, M.; Freitag, M.; Kupfer, R.; van den Bogaard, M.; Stamminger, T. Direct targeting of human cytomegalovirus protein kinase pUL97 by kinase inhibitors is a novel principle of antiviral therapy. J. Gen. Virol. 2002, 83, 1013-1023.
10. Michel, D.; Mertens, T. The UL97 protein kinase of human cytomegalovirus and homologues in other herpesviruses: impact on virus and host. Biochim. Biophys. Acta 2004, 1697, 169-180.
11. Purves, F. C.; Roizman, B. The UL13 gene of herpes simplex virus 1 encodes the functions for post-translational processing associated with phosphorylation of the regulatory protein α22. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 7310-7314.
12. Prichard, M. N.; Gao, N.; Jairath, S.; Mulamba, G.; Krosky, P.; Coen, D. M.; Parker, B. O.; Pari, G. S. A recombinant human cytomegalovirus with a large deletion in UL97 has a severe replication deficiency. J. Virol. 1999, 73, 5663-5670.
13. Chee, M. S.; Lawrence, G. L.; Barrell, B. G. Alpha-, beta- and gammaherpesviruses encode a putative phosphotransferase. J. Gen. Virol. 1989, 70, 1151-1160.
14. Ginalski, K.; Elofsson, A.; Fischer, D.; Rychlewski, L. 3D-Jury: a simple approach to improve protein structure predictions. Bioinformatics 2003, 19, 1015-1018.
15. Hanks, S. K.; Hunter, T. Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB J. 1995, 9, 576-596.
16. Hanks, S. K.; Quinn, A. M.; Hunter, T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 1988, 241, 42-52.
17. Pevarello, P.; Brasca, M. G.; Amici, R.; Orsini, P.; Traquandi, G.; Corti, L.; Piutti, C.; Sansonna, P.; Villa, M.; Pierce, B. S.; Pulici, M.; Giordano, P.; Martina, K.; Fritzen, E. L.; Nugent, R. A.; Casale, E.; Cameron, A.; Ciomei, M.; Roletto, F.; Isacchi, A.; Fogliatto, G.; Pesenti, E.; Pastori, W.; Marsiglio, A.; Leach, K. L.; Clare, P. M.; Fiorentini, F.; Varasi, M.; Vulpetti, A.; Warpehoski, M. A. 3-Aminopyrazole inhibitors of CDK2/ cyclin A as antitumor agents. J. Med. Chem. 2004, 47, 3367-3380.
18. Erice, A. Resistance of human cytomegalovirus to antiviral drugs. Clin. Microbiol. Rev. 1999, 12, 286-297.
19. Marschall, M.; Stein-Gerlach, M.; Freitag, M.; Kupfer, R.; van den Bogaard, M.; Stamminger, T. Inhibitors of human cytomegalovirus replication drastically reduce the activity of the viral protein kinase pUL97. J. Gen. Virol. 2001, 82, 1439-1450.
20. Kawaguchi, Y.; Van, Sant, C.; Roizman, B. Eukaryotic elongation factor 1δ is hyperphosphorylated by the protein kinase encoded by the UL13 gene of herpes simplex virus 1. J. Virol. 1998, 72, 1731-1736.
21. Kawaguchi, Y.; Kato, K.; Tanaka, M.; Kanamori, M.; Nishiyama, Y.; Yamanashi, Y. Conserved protein kinases encoded by herpesviruses and cellular protein kinase cdc2 target the same phosphorylation site in eukaryotic elongation factor 1δ. J. Virol. 2003, 77, 2359-2368.
22. Advani, S. J.; Weichselbaum, R. R.; Roizman, B. Cdc2 cyclin-dependent kinase binds and phosphorylates herpes simplex virus UL42 DNA synthesis processivity factor. J. Virol. 2001, 75, 10326-10333.
23. Daikoku, T.; Shibata, S.; Goshima, F.; Oshima, S.; Tsurumi, T.; Yamada, H.; Yamashita, Y.; Nishiyama, Y. Purification and characterization of the protein kinase encoded by the UL13 gene of herpes simplex virus type 2. Virology 1997, 235, 82-93.
24. Herget, T.; Freitag, M.; Morbitzer, M.; Stamminger, T.; Marschall, M. A novel chemical class of pUL97 protein kinase-specific inhibitors with strong anti-cytomegaloviral activity. Antimicrob. Agents Chemother. 2004, 48, 4154-4162.
25. Long, M. C.; Leong, V.; Schaffer, P. A.; Spencer, C. A.; Rice, S. A. ICP22 and the UL13 protein kinase are both required for herpes simplex virus-induced modification of the large subunit of RNA polymerase II. J. Virol. 1999, 73, 5593-5604.
26. Park, R.; Baines, J. D. Herpes simplex virus type 1 infection induces activation and recruitment of protein kinase C to the nuclear membrane and increased phosphorylation of lamin B. J. Virol. 2006, 80, 494-504.
27. Ng, T. I.; Talarico, C.; Burnette, T. C.; Biron, K.; Roizman, B. Partial substitution of the functions of the herpes simplex virus UL13 gene by the human cytomegalovirus UL97 gene. Virology 1996, 225, 347-358.
28. Kato, A.; Yamamoto, M.; Ohno, T.; Tanaka, M.; Sata, T.; Nishiyama, Y.; Kawaguchi, Y. Herpes simplex virus 1-encoded protein kinase UL13 phosphorylates viral Us3 protein kinase and regulates nuclear localization of viral envelopment factors UL34 and UL31. J. Virol. 2006, 80, 1476-1486.
29. Pindur, U.; Kim, Y. S.; Mehrabani, F. Advances in indolo[2,3-a]-carbazole chemistry: design and synthesis of protein kinase C and topoisomerase I inhibitors. Curr. Med. Chem. 1999, 6, 29-69.
30. Herget, T.; Marschall, M. Anti-herpesviral combination therapy based on protein kinase inhibitors. In New Concepts of Antiviral Therapy; Holzenburg, A., and Bogner, E., Eds.; Springer: London, U.K., 2006; pp 351-371.
31. Xu, Z. B.; Chaudhary, D.; Olland, S.; Wolfrom, S.; Czerwinski, R.; Malakian, K.; Lin, L.; Stahl, M. L.; Joseph-McCarthy, D.; Benander, C.; Fitz, L.; Greco, R.; Somers, W. S.; Mosyak, L. Catalytic domain crystal structure of protein kinase C-theta (PKC theta). J. Biol. Chem. 2004, 279, 50401-50409.
32. Chee, M. S.; Bankier, A. T.; Beck, S.; Bohni, R.; Brown, C. M.; Cerny, R.; Horsnell, T.; Hutchison, C. A., III; Kouzarides, T.; Martignetti, J. A.; Preddie, E.; Satchwell, S. C.; Tomlinson, P.; Weston, K. M.; Barrell, B. G. Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169. Curr. Top. Microbiol. Immunol. 1990, 154, 125-169.
33. Vink, C.; Beuken, E.; Bruggeman, C. A. Complete DNA sequence of the rat cytomegalovirus genome. J. Virol. 2000, 74, 7656-7665.
34. Smith, R. F.; Smith, T. F. Identification of new protein kinase-related genes in three herpesviruses, herpes simplex virus, varicella-zoster virus, and Epstein-Barr virus. J. Virol. 1989, 63, 450-455.
35. McGeoch, D. J.; Dalrymple, M. A.; Davison, A. J.; Dolan, A.; Frame, M. C.; McNab, D.; Perry, L. J.; Scott, J. E.; Taylor, P. The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. J. Gen. Virol. 1988, 69, 1531-1574.
36. Lambert, C.; Leonard, N.; De, Bolle, X.; Depiereux, E. ESyPred3D: Prediction of protein 3D structures. Bioinformatics 2002, 18, 1250-1256.
37. Wallner, B.; Elofsson, A. Can correct protein models be identified? Protein Sci. 2003, 12, 1073-1086.
38. McGuffin, L. J.; Bryson, K.; Jones, D. T. The PSIPRED protein structure prediction server. Bioinformatics 2000, 16, 404-405.
39. Wallace, A. C.; Laskowski, R. A.; Thornton, J. M. LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng. 1995, 8, 127-134.
40. Chartier, C.; Degryse, E.; Gantzer, M.; Dieterle, A.; Pavirani, A.; Mehtali, M. Efficient generation of recombinant adenovirus vectors by homologous recombination in Escherichia coli. J. Virol. 1996, 70, 4805-4810.
41. Michou, A. I.; Lehrmann, H.; Saltik, M.; Cotten, M. Mutational analysis of the avian adenovirus CELO, which provides a basis for gene delivery vectors. J. Virol. 1999, 73, 1399-1410.
42. Tsai, L. H.; Harlow, E.; Meyerson, M. Isolation of the human Cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase. Nature 1991, 353, 174-177.
43. Stein, B.; Yang, M. X.; Young, D. B.; Janknecht, R.; Hunter, T.,; Murray, B. W.; Barbosa, M. S. p38-2., a novel mitogen-activated protein kinase with distinct properties. J. Biol. Chem. 1997, 272, 19509-19517.
44. Finkenzeller, G.; Marme, D.; Hug, H. Sequence of human protein kinase C α. Nucleic Acids Res. 1990, 18, 2183.
45. Brauninger, A.; Karn, T.; Strebhardt, K.; Rübsamen-Waigmann, H. Characterization of the human CSK locus. Oncogene 1993, 8, 1365-1369.
46. Krosky, P. M.; Baek, M. C.; Jahng, W. J.; Barrera, I.; Harvey, R. J.; Biron, K. K.; Coen, D. M.; Sethna, P. B. The human cytomegalovirus UL44 protein is a substrate for the UL97 protein kinase. J. Virol. 2003, 77, 7720-7727.
47. Michel, D.; Kramer, S.; Hohn, S.; Schaarschmidt, P.; Wunderlich, K.; Mertens, T. Amino acids of conserved kinase motifs of cytomegalovirus protein UL97 are essential for autophosphorylation. J. Virol. 1999, 73, 8898-8901.
48. Chen, M. R.; Chang, S. J.; Huang, H.; Chen, J. Y. A protein kinase activity associated with Epstein Barr virus BGLF4 phosphorylates the viral early antigen EA-D in vitro. J. Virol. 2000, 74, 3093-3104.
49. Gershburg, E.; Pagano, J. S. Phosphorylation of the Epstein Barr virus (EBV) DNA polymerase processivity factor EA-D by the EBV-encoded protein kinase and effects of the L-riboside benzimidazole 1263W94. J. Virol. 2002, 76, 998-1003.
50. Kato, K.; Kawaguchi, Y.; Tanaka, M.; Igarashi, M.; Yokoyama, A.; Matsuda, G.; Kanamori, M.; Nakajima, K.; Nishimura, Y.; Shimojima, M.; Phung, H. T. T.; Takahashi, E.; Hirai, K. Epstein-Barr virus-encoded protein kinase BGLF4 mediates hyperphosphorylation of cellular elongation factor 1δ (EF-1δ): EF-1δ is universally modified by conserved protein kinases of herpesviruses in mammalian cells. J. Gen. Virol. 2001, 82, 1457-1463.