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Human Cytomegalovirus의 UL97 단백질 인산화 효소의 기질 특이성 연구를 위한 Peptide Library의 스크리닝
Screening of Peptide Libraries to Investigate the Substrate Specificity of UL97 Protein Kinase from Human Cytomegalovirus

백문창    (경북대학교 의과대학 분자의학교실  );
  • 초록

    Human cytomegalovirus encodes an unusual protein kinase UL97 which can phosphorylate exogenous substrates, including histone H2B and nucleoside analogs such as ganciclovir. The previous result interestingly showed that the peptides phosphorylated by UL97 have K/R at the 5 positions (P+5) downstream from the pSer. To confirm the importance of the basic residue in the position, we used two peptide libraries, 4S4K (MAXXXXSXXXXKXANNN) and 4S6N (MAXXXXSXXXXXXNNN). The activity of phosphorylation by UL97 was higher in the peptide library 4S4K than 4S6N, suggesting the importance of basic residue at P+5 position. The screening with a peptide library 4S4K showed slight tendencies for N in the P+1 and P+2, M in the P+2, K in the P+4 and P+6 positions and several amino acids in the other positions. This result will give information to develop an optimal peptide for screening a novel UL97 inhibitor.


  • 주제어

    Human cytomegalovirus .   Protein kinase UL97 .   Peptide substrate .   Peptide library.  

  • 참고문헌 (24)

    1. Biron KK, Harvey RJ, Chamberlain SC, Good SS, Smith AA 3rd, Davis MG, Talarico CL, Miller WH, Ferris R, Dornsife RE, Stanat SC, Drach JC, Townsend LB, Koszalka GW: Interactions of 1263W94 with other antiviral agents in inhibition of human cytomegalovirus replication. Antimicrob Agents Chemother 47: 1468-1471, 2003 
    2. He Z, He YS, Kim Y, Chu L, Ohmstede C, Biron KK, Coen DM: The human cytomegalovirus UL97 protein is a protein kinase that autophosphorylates on serines and threonines. J Virol 71: 405-411, 1997 
    3. Johnson LN, Lowe ED, Noble ME, Owen DJ: The Eleventh Datta Lecture. The structural basis for substrate recognition and control by protein kinases. FEBS Lett 430: 1-11, 1998 
    4. Selleseth DW, Talarico CL, Miller T, Lutz MW, Biron KK, Harvey RJ: In vitro activities of benzimidazole D- and L-ribonucleosides against herpesviruses. Antimicrob Agents Chemother 47: 2186-2192, 2003 
    5. Songyang Z, Blechner S, Hoagland N, Hoekstra MF, Piwnica-Worms H, Cantley LC: Use of an oriented peptide library to determine the optimal substrates of protein kinases. Curr Biol 4: 973-982, 1994 
    6. Songyang Z, Lu KP, Kwon YT, Tsai L-H, Filhol 0, Cochet C, Brickey DA, Soderling TR, Bartleson C, Graves DJ, Demaggio AJ, Hoekstra MF, Blenis J, Hunter T, Cantley LC: A structural basis for substrate specificities of protein Ser!Thr kinases: primal)' sequence preference of casein kinases I and II, NIMA, phosphorylase kinase, calmodulin-dependent kinase II, CDK5, and Erk. Mol. Cell. BioI 16: 6486-6493, 1996 
    7. Talarico CL, Burnette TC, Miller WH, Smith SL, Davis MG, Stanat SC, Ng TI, He Z, Coen DM, Roizman B, Biron KK: Acyclovir is phosphorylated by the human cytomegalovirus UL97 protein. Antimicrob Agents Chemother 43: 1941-1946, 1999 
    8. Chee MS, Lawrence GL, Barrell BG: Alpha-, beta- and gammaherpesviruses encode a putative phosphotransferase. J Gen Virol 70: 1151-1160, 1989 
    9. Krosky PM, Baek MC, Coen DM: The human cytomegalovirus UL97 protein kinase, an antiviral drug target, is required at the stage of nuclear egress. J Viral 77: 905-914, 2003 
    10. McGeoch DJ, Coulter LJ, Moss HWM: Vol. 1, pp. 391-393, In The Protein Kinase Facts Book, Hardie, G., and Hanks, S.(Ed), Academic Press, London, 1995 
    11. Baek MC, Krosky PM, Coen DM: Relationship between autophosphorylation and phosphorylation of exogenous substrates by the human cytomegalovirus UL97 protein kinase. J Virol 76: 11943-11952, 2002 
    12. Baek MC, Krosky PM, He Z, Coen DM: Specific phosphorylation of exogenous protein and peptide substrates by the human cytomegalovirus UL97 protein kinase. Importance of the P+5 position. J Biol. Chem 277: 29593-29599, 2002 
    13. Crossen, R., and Gruenwald, S: In Baculovirus Expression Vector System Manual, 5th ed. Phanningen, San Diego, 1998 
    14. Songyang Z, Cantley LC: The use of peptide library for the determination of kinase peptide substrates. Methods Mol Biol 87: 87-98, 1998 
    15. Wolf DG, Courcelle CT, Prichard MN, Mocarski ES: Distinct and separate roles for herpesvirus-conserved UL97 kinase in cytomegalovirus DNA synthesis and encapsidation. Proc Natl Acad Sci USA. 98: 1895-1900, 2001 
    16. Taylor SS, Radzio-Andzelm E, Hunter T: How do protein kinases discriminate between serine/threonine and tyrosine? Structural insights from the insulin receptor protein-tyrosine kinase. FASEB J 9: 1255-1266, 1995 
    17. Sullivan V, Talarico CL, Stanat SC, Davis M, Coen DM, Biron KK: A protein kinase homologue controls phosphorylation of ganciclovir in human cytomegalovirus-infected cells. Nature 358: 162-164, 1992 
    18. Krosky PM, Baek MC, Jahng WJ, Barrera I, Harvey RJ, Biron KK, Coen DM, Sethna PB: The human cytomegalovirus UL44 protein is a substrate for the UL97 protein kinase. J Virol 77: 7720-7727, 2003 
    19. Hanks SK, Hunter T: Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB J 9: 576-596, 1995 
    20. Biron KK, Harvey RJ, Chamberlain SC, Good SS, Smith AA 3rd, Davis MG, Talarico CL, Miller WH, Ferris R, Dornsife RE, Stanat SC, Drach JC, Townsend LB, Koszalka GW Potent and selective inhibition of human cytomegalovirus replication by 1263W94, a benzimidazole L-riboside with a unique mode of action. Antimicrob Agents Chemother 46: 2365-2372, 2002 
    21. Johnson LN, Noble ME, Owen DJ: Active and inactive protein kinases: structural basis for regulation. Cell 85: 149 -158, 1996 
    22. Hayden FG: Antiviral agents (nonretroviral), pp. 1313-1347. In Goodman & Gilman's The pharmacological basis of therapeutics, 10th ed, J.G. Hardman, L.E. Limbird, and A. G. Gilman (Ed.), McGraw-Hill, New York, N.Y. 2001 
    23. Prichard MN, Gao N, Jairath S, Mulamba G, Krosky P, Coen DM, Parker BO, Pari GS: A recombinant human cytomegalovirus with a large deletion in UL97 has a severe replication deficiency. J Viral 73: 5663-5670, 1999 
    24. Littler E, Stuart AD, Chee MS: Human cytomegalovirus UL97 open reading frame encodes a protein that phosphorylates the antiviral nucleoside analogue ganciclovir. Nature 358: 160-162, 1992 

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