Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.1 (
protein kinase
)
81,284
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Acyclovir
(
ACV
) has shown efficacy in the prophylactic suppression of human cytomegalovirus (HCMV) reactivation in immunocompromised renal transplant patients without the toxicity associated with ganciclovir (GCV). The HCMV UL97 gene product, a
protein kinase
, is responsible for the phosphorylation of GCV in HCMV-infected cells. This report provides evidence for the phosphorylation of
ACV
by UL97. Anabolism studies with the HCMV wild-type strain AD169 and with recombinant mutants derived from marker transfer experiments performed by using mutant UL97 DNA from both clinical isolates and a laboratory-derived strain resistant to GCV showed that mutations in the UL97 gene cripple the ability of recombinant virus-infected cells to anabolize both GCV and
ACV
. These mutant UL97 recombinant viruses were less susceptible to both GCV and
ACV
than was the wild-type strain. A recombinant herpes simplex virus type 1 strain, in which the thymidine kinase gene is deleted and the UL13 gene is replaced with the HCMV UL97 gene, was able to induce the phosphorylation of
ACV
in infected cells. Finally, purified UL97 phosphorylated both GCV and
ACV
to their monophosphates. Our results indicate that UL97 promotes the selective activity of
ACV
against HCMV.
...
PMID:Acyclovir is phosphorylated by the human cytomegalovirus UL97 protein. 1042 17