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Human cytomegalovirus expresses an unusual protein kinase UL97, a member of ${H_V}{U_L}$ family of protein kinase. UL97 can phosphorylate nucleoside analogs such as ganciclovir as well as protein/peptide. It has previously been reported that UL97 is able to phosphorylate a KESYSVYVYKV peptide and that P+5 position (K) is important. We examined the extent of contribution of other positions (P-4 through P+6) of the peptide to be substrate of UL97 using alanine substituted peptides (Ala scanning) and deleted peptides. The result suggested that the E (P-2) is negative effect and P+5 (K) is still important. The peptide YSVYVYK is the shortest substrate enough to show high activity, which could be a starting point to develop peptidomimetic drug. This study would give important information to deeply understand the substrate specificity of UL97 and develop an antiviral drug using the small peptide identified here.
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참고문헌 (14)
참고문헌 신청
Littler, E. / 1992 / Human cytomegalovirus UL97 open reading frame encodes a protein that phosphorylates the antiviral nucleoside analogue ganciclovir / Nature 358:160
Sullivan, V. / 1992 / A protein kinase homologue controls phosphorylation of ganciclovir in human cytomegalovirusinfected cells / Nature 358:162
Krosky, P. M. / 2003 / The human cytomegalovirus UL97 protein kinase, an antiviral drug target, is required at the stage of nuclear egress / J. Virol 77:905
Wolf, D. G. / 2001 / Distinct and separate roles for herpesvirus-conserved UL97 kinase in cytomegalovirus DNA synthesis and encapsidation / Proc. Natl. Acad. Sci. U.S.A 98:1895
Biron, K. K. / 2002 / 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
Sullivan, V. / 1992 / A protein kinase homologue controls phosphorylation of ganciclovir in human cytomegalovirusinfected cells / Nature 358:162
Krosky, P. M. / 2003 / The human cytomegalovirus UL97 protein kinase, an antiviral drug target, is required at the stage of nuclear egress / J. Virol 77:905
Wolf, D. G. / 2001 / Distinct and separate roles for herpesvirus-conserved UL97 kinase in cytomegalovirus DNA synthesis and encapsidation / Proc. Natl. Acad. Sci. U.S.A 98:1895
Biron, K. K. / 2002 / 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
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