Alkyltransferase-like protein (Atl1) distinguishes alkylated guanines for DNA repair using cation–π interactions
| العنوان: | Alkyltransferase-like protein (Atl1) distinguishes alkylated guanines for DNA repair using cation–π interactions |
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| المؤلفون: | Julie L. Tubbs, Geoffrey P. Margison, Bernard A. Connolly, Hannah Blackburn, Christopher L. Millington, Mary R Thorncroft, David M. Williams, Oliver J. Wilkinson, Christopher A. Hunter, John A. Tainer, Andrew S. Marriott, Rihito Morita, Gail McGown, Ryoji Masui, Jane A. Grasby, Vitaly F. Latypov, Amanda J. Watson |
| المصدر: | Proceedings of the National Academy of Sciences. 109:18755-18760 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Guanine, Alkylation, DNA Repair, DNA repair, Mutation, Missense, Crystallography, X-Ray, chemistry.chemical_compound, Bacterial Proteins, Schizosaccharomyces, Alkyl and Aryl Transferases, Multidisciplinary, biology, Thermus thermophilus, Biological Sciences, biology.organism_classification, Protein Structure, Tertiary, DNA Alkylation, Amino Acid Substitution, Oligodeoxyribonucleotides, Biochemistry, chemistry, Schizosaccharomyces pombe, Schizosaccharomyces pombe Proteins, Protein Binding, Alkyltransferase, Nucleotide excision repair |
| الوصف: | Alkyltransferase-like (ATL) proteins in Schizosaccharomyces pombe (Atl1) and Thermus thermophilus (TTHA1564) protect against the adverse effects of DNA alkylation damage by flagging O 6 -alkylguanine lesions for nucleotide excision repair (NER). We show that both ATL proteins bind with high affinity to oligodeoxyribonucleotides containing O 6 -alkylguanines differing in size, polarity, and charge of the alkyl group. However, Atl1 shows a greater ability than TTHA1564 to distinguish between O 6 -alkylguanine and guanine and in an unprecedented mechanism uses Arg69 to probe the electrostatic potential surface of O 6 -alkylguanine, as determined using molecular mechanics calculations. An unexpected consequence of this feature is the recognition of 2,6-diaminopurine and 2-aminopurine, as confirmed in crystal structures of respective Atl1-DNA complexes. O 6 -Alkylguanine and guanine discrimination is diminished for Atl1 R69A and R69F mutants, and S. pombe R69A and R69F mutants are more sensitive toward alkylating agent toxicity, revealing the key role of Arg69 in identifying O 6 -alkylguanines critical for NER recognition. |
| تدمد: | 1091-6490 0027-8424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aefb71f80de8a217758a25dc55b8ef72 https://doi.org/10.1073/pnas.1209451109 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....aefb71f80de8a217758a25dc55b8ef72 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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