Synthesis, solution and crystal structure of the coenzyme B(12) analogue Co(β)-2'-fluoro-2',5'-dideoxyadenosylcobalamin
| Autor: | Miriam Hunger, Klaus Wurst, Bernhard Kräutler |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
chemistry.chemical_classification
Cofactor binding Magnetic Resonance Spectroscopy biology Molecular Structure Coenzyme B Stereochemistry Circular Dichroism Active site Fluorine-19 NMR Crystal structure Fluorine Alkylation Crystallography X-Ray Biochemistry Cofactor Inorganic Chemistry Solutions chemistry.chemical_compound Vitamin B 12 Enzyme chemistry Models Chemical biology.protein Cobamides |
| Zdroj: | Journal of inorganic biochemistry. 148 |
| ISSN: | 1873-3344 |
| Popis: | Crystal structure analyses have helped to decipher the mode of binding of coenzyme B12 (AdoCbl) in the active site of AdoCbl-dependent enzymes. However, the question of how such enzymes perform their radical reactions is still incompletely answered. A pioneering study by Gruber and Kratky of AdoCbl-dependent glutamate mutase (GLM) laid out a path for the movement of the catalytically active 5′-deoxyadenosyl radical, in which H-bonds between the protein and the 2′- and 3′-OH groups of the protein bound AdoCbl would play a decisive role. Studies with correspondingly modified coenzyme B12-analogues are of interest to gain insights into cofactor binding and enzyme mechanism. Here we report the preparation of Coβ-2′-fluoro-2′,5′-dideoxyadenosylcobalamin (2′FAdoCbl), which lacks the 2′-OH group critical for the interaction in enzymes. 2′FAdoCbl was prepared by alkylation of cob(I)alamin, obtained from the electrochemical reduction of aquocobalamin. Spectroscopic data and a single crystal X-ray analysis of 2′FAdoCbl established its structure, which was very similar to that one of coenzyme B12. 2′FAdoCbl is a 19F NMR active mimic of coenzyme B12 that may help to gain insights into binding interactions of coenzyme B12 with AdoCbl-dependent enzymes, proteins of B12 transport and of AdoCbl-biosynthesis, as well as with B12-riboswitches. |
| Databáze: | OpenAIRE |
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