3GVA

Crystal Structure Analysis of S. Pombe ATL

3GVA の概要

• エントリーDOI: 10.2210/pdb3gva/pdb
• 分子名称: Alkyltransferase-like protein 1 (2 entities in total)
• 機能のキーワード: alkylated dna damage repair, dna damage, dna repair, dna-binding, dna binding protein
• 由来する生物種: Schizosaccharomyces pombe (Fission yeast)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27324.82

構造登録者

Tubbs, J.L.,Arvai, A.S.,Tainer, J.A. (登録日: 2009-03-30, 公開日: 2009-06-09, 最終更新日: 2024-02-21)

主引用文献

Tubbs, J.L.,Latypov, V.,Kanugula, S.,Butt, A.,Melikishvili, M.,Kraehenbuehl, R.,Fleck, O.,Marriott, A.,Watson, A.J.,Verbeek, B.,McGown, G.,Thorncroft, M.,Santibanez-Koref, M.F.,Millington, C.,Arvai, A.S.,Kroeger, M.D.,Peterson, L.A.,Williams, D.M.,Fried, M.G.,Margison, G.P.,Pegg, A.E.,Tainer, J.A.
Flipping of alkylated DNA damage bridges base and nucleotide excision repair.
Nature, 459:808-813, 2009

PubMed Abstract: Alkyltransferase-like proteins (ATLs) share functional motifs with the cancer chemotherapy target O(6)-alkylguanine-DNA alkyltransferase (AGT) and paradoxically protect cells from the biological effects of DNA alkylation damage, despite lacking the reactive cysteine and alkyltransferase activity of AGT. Here we determine Schizosaccharomyces pombe ATL structures without and with damaged DNA containing the endogenous lesion O(6)-methylguanine or cigarette-smoke-derived O(6)-4-(3-pyridyl)-4-oxobutylguanine. These results reveal non-enzymatic DNA nucleotide flipping plus increased DNA distortion and binding pocket size compared to AGT. Our analysis of lesion-binding site conservation identifies new ATLs in sea anemone and ancestral archaea, indicating that ATL interactions are ancestral to present-day repair pathways in all domains of life. Genetic connections to mammalian XPG (also known as ERCC5) and ERCC1 in S. pombe homologues Rad13 and Swi10 and biochemical interactions with Escherichia coli UvrA and UvrC combined with structural results reveal that ATLs sculpt alkylated DNA to create a genetic and structural intersection of base damage processing with nucleotide excision repair.

PubMed: 19516334
DOI: 10.1038/nature08076

実験手法

X-RAY DIFFRACTION (2 Å)