Reaction of human UMP-CMP kinase with natural and analog substrates
| Autor: | Sarah Gallois-Montbrun, Anne-Marie Gilles, Michel Véron, Dominique Deville-Bonne, Claudia Pasti, Hélène Munier-Lehmann |
|---|---|
| Přispěvatelé: | Régulation Enzymatique des Activités Cellulaires, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Chimie Structurale des Macromolécules (CSM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2003 |
| Předmět: |
[SDV]Life Sciences [q-bio]
Recombinant Fusion Proteins Molecular Sequence Data Biochemistry Polymerase Chain Reaction Substrate Specificity Cytidine Monophosphate Humans Nucleotide Cloning Molecular MAPK14 DNA Primers chemistry.chemical_classification biology Base Sequence Kinase Cyclin-dependent kinase 3 Active site Substrate (chemistry) carbohydrates (lipids) Kinetics Enzyme chemistry biology.protein Phosphorylation Nucleoside-Phosphate Kinase Uridine Monophosphate |
| Zdroj: | European Journal of Biochemistry European Journal of Biochemistry, 2003, 270 (8), pp.1784-90. ⟨10.1046/j.1432-1033.2003.03537.x⟩ European Journal of Biochemistry, Wiley, 2003, 270 (8), pp.1784-90. ⟨10.1046/j.1432-1033.2003.03537.x⟩ |
| ISSN: | 0014-2956 1432-1327 |
| Popis: | International audience; UMP-CMP kinase catalyses an important step in the phosphorylation of UTP, CTP and dCTP. It is also involved in the necessary phosphorylation by cellular kinases of nucleoside analogs used in antiviral therapies. The reactivity of human UMP-CMP kinase towards natural substrates and nucleotide analogs was reexamined. The expression of the recombinant enzyme and conditions for stability of the enzyme were improved. Substrate inhibition was observed for UMP and CMP at concentrations higher than 0.2 mm, but not for dCMP. The antiviral analog l-3TCMP was found to be an efficient substrate phosphorylated into l-3TCDP by human UMP-CMP kinase. However, in the reverse reaction, the enzyme did not catalyse the addition of the third phosphate to l-3TCDP, which was rather an inhibitor. By molecular modelling, l-3TCMP was built in the active site of the enzyme from Dictyostelium. Human UMP-CMP kinase has a relaxed enantiospecificity for the nucleoside monophosphate acceptor site, but it is restricted to d-nucleotides at the donor site. |
| Databáze: | OpenAIRE |
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