5FIU
Binding and structural studies of a 5,5-difluoromethyl adenosine nucleoside with the fluorinase enzyme
Summary for 5FIU
Entry DOI | 10.2210/pdb5fiu/pdb |
Descriptor | 5'-FLUORO-5'-DEOXY-ADENOSINE SYNTHASE, 5,5-DIFLUOROMETHYL ADENOSINE, L(+)-TARTARIC ACID, ... (4 entities in total) |
Functional Keywords | transferase, fluorinase, difluoromethyl, isothermal titration calorimetry |
Biological source | STREPTOMYCES CATTLEYA |
Total number of polymer chains | 3 |
Total formula weight | 98516.40 |
Authors | Thompson, S.,McMahon, S.A.,Naismith, J.H.,O'Hagan, D. (deposition date: 2015-10-02, release date: 2015-12-23, Last modification date: 2024-01-10) |
Primary citation | Thompson, S.,Mcmahon, S.A.,Naismith, J.H.,O'Hagan, D. Exploration of a Potential Difluoromethyl-Nucleoside Substrate with the Fluorinase Enzyme. Bioorg.Chem., 64:37-, 2015 Cited by PubMed Abstract: The investigation of a difluoromethyl-bearing nucleoside with the fluorinase enzyme is described. 5',5'-Difluoro-5'-deoxyadenosine 7 (F2DA) was synthesised from adenosine, and found to bind to the fluorinase enzyme by isothermal titration calorimetry with similar affinity compared to 5'-fluoro-5'-deoxyadenosine 2 (FDA), the natural product of the enzymatic reaction. F2DA7 was found, however, not to undergo the enzyme catalysed reaction with L-selenomethionine, unlike FDA 2, which undergoes reaction with L-selenomethionine to generate Se-adenosylselenomethionine. A co-crystal structure of the fluorinase and F2DA7 and tartrate was solved to 1.8Å, and revealed that the difluoromethyl group bridges interactions known to be essential for activation of the single fluorine in FDA 2. An unusual hydrogen bonding interaction between the hydrogen of the difluoromethyl group and one of the hydroxyl oxygens of the tartrate ligand was also observed. The bridging interactions, coupled with the inherently stronger C-F bond in the difluoromethyl group, offers an explanation for why no reaction is observed. PubMed: 26642178DOI: 10.1016/J.BIOORG.2015.11.003 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.84 Å) |
Structure validation
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