Recognition of oxidatively modified bases within the biotin-binding site of avidin
| Autor: | R.L. Brady, E. Hooley, S. Thomas, Rebecca Conners, AR Clarke |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Models
Molecular Biotin binding DNA damage Molecular Sequence Data Biotin Crystallography X-Ray chemistry.chemical_compound Structural Biology A-DNA Molecular Biology Binding Sites biology Deoxyadenosines Molecular Structure Oligonucleotide Deoxyguanosine DNA Avidin Protein Structure Tertiary Biochemistry chemistry 8-Hydroxy-2'-Deoxyguanosine Biotinylation biology.protein Nucleic Acid Conformation Oxidation-Reduction Protein Binding |
| Zdroj: | Journal of molecular biology. 357(1) |
| ISSN: | 0022-2836 |
| Popis: | Oxidative damage of DNA results in the formation of many products, including 8-oxodeoxyguanosine, which has been used as a marker to quantify DNA damage. Earlier studies have demonstrated that avidin, a protein prevalent in egg-white and which has high affinity for the vitamin biotin, binds to 8-oxodeoxyguanosine and related bases. In this study, we have determined crystal structures of avidin in complex with 8-oxodeoxyguanosine and 8-oxodeoxyadenosine. In each case, the base is observed to bind within the biotin-binding site of avidin. However, the mode of association between the bases and the protein varies and, unlike in the avidin:biotin complex, complete ordering of the protein in this region does not accompany binding. Fluorescence studies indicate that in solution the individual bases, and a range of oligonucleotides, bind to avidin with micromolar affinity. Only one of the modes of binding observed is consistent with recognition of oxidised purines when incorporated within a DNA oligomer, and from this structure a model is proposed for the selective binding of avidin to DNA containing oxidatively damaged deoxyguanosine. These studies illustrate the molecular basis by which avidin might act as a marker of DNA damage, although the low levels of binding observed are inconsistent with the recognition of oxidised purines forming a major physiological role for avidin. |
| Databáze: | OpenAIRE |
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