4HDV

Crystal structure of S. pombe ATL1 in complex with damaged DNA containing 2,6-diaminopurine

4HDV の概要

• エントリーDOI: 10.2210/pdb4hdv/pdb
• 関連するPDBエントリー: 4HDU
• 分子名称: Alkyltransferase-like protein 1, 5'-D(*GP*CP*CP*AP*TP*GP*(1AP)P*CP*TP*AP*GP*TP*A)-3', 5'-D(*CP*TP*AP*CP*TP*AP*GP*CP*CP*AP*TP*GP*G)-3', ... (4 entities in total)
• 機能のキーワード: alkyltransferase, dna repair, nucleotide excision repair, ner, base repair, dna damage, guanine, alkylation, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Schizosaccharomyces pombe (Fission yeast)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 21604.62

構造登録者

Tubbs, J.L.,Tainer, J.A. (登録日: 2012-10-02, 公開日: 2012-12-26, 最終更新日: 2023-09-20)

主引用文献

Wilkinson, O.J.,Latypov, V.,Tubbs, J.L.,Millington, C.L.,Morita, R.,Blackburn, H.,Marriott, A.,McGown, G.,Thorncroft, M.,Watson, A.J.,Connolly, B.A.,Grasby, J.A.,Masui, R.,Hunter, C.A.,Tainer, J.A.,Margison, G.P.,Williams, D.M.
Alkyltransferase-like protein (Atl1) distinguishes alkylated guanines for DNA repair using cation-{pi} interactions.
Proc.Natl.Acad.Sci.USA, 109:18755-18760, 2012

PubMed Abstract: 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.

PubMed: 23112169
DOI: 10.1073/pnas.1209451109

実験手法

X-RAY DIFFRACTION (2.702 Å)