A protein kinase homologue controls phosphorylation of ganciclovir in human cytomegalovirus-infected cells
| Autor: | Christine L. Talarico, Karen K. Biron, Sylvia C. Stanat, Michele Davis, V. Sullivan, Donald M. Coen |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Ganciclovir
Human cytomegalovirus viruses Molecular Sequence Data Drug Resistance Cytomegalovirus Mitogen-activated protein kinase kinase Transfection MAP2K7 medicine Humans Amino Acid Sequence Cloning Molecular Phosphorylation Protein kinase A Cells Cultured Multidisciplinary Base Sequence biology Kinase Phosphotransferases Cyclin-dependent kinase 2 virus diseases Maribavir Fibroblasts biochemical phenomena metabolism and nutrition medicine.disease Virology Phosphotransferases (Alcohol Group Acceptor) DNA Viral biology.protein Protein Kinases Plasmids medicine.drug |
| Zdroj: | Nature. 358:162-164 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/358162a0 |
| Popis: | HUMAN cytomegalovirus (HCMV) is a major pathogen in immunosuppressed individuals, including patients with acquired immune deficiency syndrome. The nucleoside analogue ganciclovir (9-(l,3-dihydroxy-2-propoxymethyl)-guanine) is one of the few drugs available to treat HCMV infections, but resistant virus is a growing problem in the clinic1 and there is a critical need for new drugs. The study of ganciclovir-resistant mutants has indicated that the selective action of ganciclovir depends largely on virus-controlled phosphorylation in HCMV-infected cells2–5. The enzyme(s) responsible have not been identified. Here we report that the HCMV gene UL97, whose predicted product shares regions of homology with protein kinases, guanylyl cyclase and bacterial phosphotransferases6–8, controls phosphorylation of ganciclovir in HCMV-infected cells. A four-amino-acid deletion of UL97 in a conserved region, which in cyclic AMP-dependent protein kinase participates in substrate recognition9, causes impaired ganciclovir phosphorylation. The implications of these results for antiviral drug development and drug resistance are discussed. |
| Databáze: | OpenAIRE |
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