Title: Phosphorylation of dGMP analogs by vaccinia virus TMP kinase and human GMP kinase
Authors: Auvynet, Constance ×
Topalis, Dimitrios
Caillat, Christophe
Munier-Lehmann, Hélène
Seclaman, Edward
Balzarini, Jan
Agrofoglio, Luigi André
Kaminski, Pierre Alexandre
Meyer, Philippe
Deville-Bonne, Dominique
El Amri, Chahrazade #
Issue Date: Oct-2009
Publisher: Academic Press
Series Title: Biochemical and Biophysical Research Communications vol:388 issue:1 pages:6-11
Abstract: Vaccinia virus thymidylate kinase, although similar in sequence to human TMP kinase, has broader substrate specificity and phosphorylates (E)-5-(2-bromovinyl)-dUMP and dGMP. Modified guanines such as glyoxal-dG, 8-oxo-dG, O(6)-methyl-dG, N(2)-ethyl-dG and N(7)-methyl-dG were found present in cancer cell DNA. Alkylated and oxidized dGMP analogs were examined as potential substrates for vaccinia TMP kinase and also for human TMP and GMP kinases. Molecular models obtained from structure-based docking rationalized the enzymatic data. All tested nucleotides are found surprisingly substrates of vaccinia TMP kinase and also of human GMP kinase. Interestingly, O(6)-methyl-dGMP is the only analog specific for the vaccinia enzyme. Thus, O(6)-Me-dGMP could be useful for designing new compounds of medical interest either in antipoxvirus therapy or in experimental combined gene/chemotherapy of cancer. These results also provide new insights regarding dGMP analog reaction with human GMP kinase and their slow recycling by salvage pathway nucleotide kinases.
ISSN: 0006-291X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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