Key motifs in EBV (Epstein-Barr virus)-encoded protein kinase for phosphorylation activity and nuclear localization

A sole EBV (Epstein-Barr virus)-encoded protein kinase (EBV-PK) (the BGLF4 eerie product) plays important roles in viral infection. Although a number of targets of this protein have been identified, the kinase itself remains lamely unstudied with regard to its enzymology and structure In the present study. site-directed mutagenesis has been employed to generate mutations targeting residues involved in nuclear localization of the EBV-PK. core residues in subdomain III of the protein kinase domain conserved in most protein kinases or residues in subdomain VIa conserved only within the HPK (herpesvirus-encoded protein kinase) group Deletion of amino acids 389-391 resulted in exclusive cytoplasmic localization of the protein, indicating the involvement of this region in nuclear translocation of the EBV-PK Mutations at the amino acids Glu(113) (core component). Phe(175) Leu(178), Phe(184), Leu(185) and Asn(186) (conserved n HPKs) resulted in loss of EBV-PK autophosphorylation, protein substrate [EBV EA-D (early antigen diffused)] phosphorylation. and ability to facilitate ganciclovir phosphorylation. These results reiterate the unique features of this group of kinases and present an opportunity for designing more specific antiviral compounds