| PMID : |
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 (19631609) |
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| titre : |
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Phosphorylation of dGMP analogs by vaccinia virus TMP kinase and human GMP kinase. |
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| auteur(s) : |
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Constance Auvynet1, Dimitri Topalis2, Christophe Caillat3, Hélène Munier-Lehmann4, Edward Seclaman4, Jan Balzarini5, Luigi André Agrofoglio6, Pierre Alexandre Kaminski7, Philippe Meyer8, Dominique Deville-Bonne2, Chahrazade El Amri ( ) 9 |
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| laboratoire : |
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| résumé : |
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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. |
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| domaine : |
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Sciences du Vivant/Biochimie, Biologie Moléculaire/Biochimie
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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0006-291X |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1016/j.bbrc.2009.07.089 |
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| journal : |
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Biochemical and Biophysical Research Communications / Biochemistry and Biophysics Research Communications |
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| Audience : |
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internationale |
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| date de publication : |
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09/10/2009 |
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date de publication
électronique : |
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23/07/2009 |
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| volume : |
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388 |
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| numéro : |
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1 |
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| page, identifiant, ... : |
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6-11 |
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