2SSP

LEUCINE-272-ALANINE URACIL-DNA GLYCOSYLASE BOUND TO ABASIC SITE-CONTAINING DNA

2SSP の概要

• エントリーDOI: 10.2210/pdb2ssp/pdb
• 分子名称: DNA (5'-D(*CP*TP*GP*TP*(AAB)P*AP*TP*CP*TP*T)-3'), DNA (5'-D(*AP*AP*AP*GP*AP*TP*AP*AP*CP*AP*G)-3'), PROTEIN (URACIL-DNA GLYCOSYLASE), ... (4 entities in total)
• 機能のキーワード: dna glycosylase, dna base excision repair, uracil, dna, protein/dna, abasic site, protein-dna complex
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Isoform 1: Mitochondrion. Isoform 2: Nucleus: P13051
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 31794.21

構造登録者

Parikh, S.S.,Mol, C.D.,Slupphaug, G.,Bharati, S.,Krokan, H.E.,Tainer, J.A. (登録日: 1999-04-28, 公開日: 1999-05-06, 最終更新日: 2023-08-02)

主引用文献

Parikh, S.S.,Mol, C.D.,Slupphaug, G.,Bharati, S.,Krokan, H.E.,Tainer, J.A.
Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA.
EMBO J., 17:5214-5226, 1998

PubMed Abstract: Three high-resolution crystal structures of DNA complexes with wild-type and mutant human uracil-DNA glycosylase (UDG), coupled kinetic characterizations and comparisons with the refined unbound UDG structure help resolve fundamental issues in the initiation of DNA base excision repair (BER): damage detection, nucleotide flipping versus extrahelical nucleotide capture, avoidance of apurinic/apyrimidinic (AP) site toxicity and coupling of damage-specific and damage-general BER steps. Structural and kinetic results suggest that UDG binds, kinks and compresses the DNA backbone with a 'Ser-Pro pinch' and scans the minor groove for damage. Concerted shifts in UDG simultaneously form the catalytically competent active site and induce further compression and kinking of the double-stranded DNA backbone only at uracil and AP sites, where these nucleotides can flip at the phosphate-sugar junction into a complementary specificity pocket. Unexpectedly, UDG binds to AP sites more tightly and more rapidly than to uracil-containing DNA, and thus may protect cells sterically from AP site toxicity. Furthermore, AP-endonuclease, which catalyzes the first damage-general step of BER, enhances UDG activity, most likely by inducing UDG release via shared minor groove contacts and flipped AP site binding. Thus, AP site binding may couple damage-specific and damage-general steps of BER without requiring direct protein-protein interactions.

PubMed: 9724657
DOI: 10.1093/emboj/17.17.5214

実験手法

X-RAY DIFFRACTION (2.25 Å)