3GP1

MutM encountering an intrahelical 8-oxoguanine (oxoG) lesion in EC3-V222P complex

3GP1 の概要

• エントリーDOI: 10.2210/pdb3gp1/pdb
• 分子名称: DNA glycosylase, 5'-D(*AP*GP*GP*TP*AP*GP*AP*TP*CP*CP*GP*GP*AP*CP*GP*CP**C)-3', 5'-D(P*TP*GP*CP*GP*TP*CP*CP*(8OG)P*GP*AP*TP*CP*TP*AP*CP*C)-3', ... (5 entities in total)
• 機能のキーワード: dna glycosylase, dna repair, damage search, base extrusion, disulfide crosslinking, dna damage, dna-binding, glycosidase, hydrolase, lyase, metal-binding, multifunctional enzyme, zinc-finger, hydrolase-dna complex, hydrolase/dna
• 由来する生物種: Geobacillus stearothermophilus; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 40171.90

構造登録者

Spong, M.C.,Qi, Y.,Verdine, G.L. (登録日: 2009-03-20, 公開日: 2009-11-10, 最終更新日: 2023-09-06)

主引用文献

Qi, Y.,Spong, M.C.,Nam, K.,Banerjee, A.,Jiralerspong, S.,Karplus, M.,Verdine, G.L.
Encounter and extrusion of an intrahelical lesion by a DNA repair enzyme
Nature, 462:762-766, 2009

PubMed Abstract: How living systems detect the presence of genotoxic damage embedded in a million-fold excess of undamaged DNA is an unresolved question in biology. Here we have captured and structurally elucidated a base-excision DNA repair enzyme, MutM, at the stage of initial encounter with a damaged nucleobase, 8-oxoguanine (oxoG), nested within a DNA duplex. Three structures of intrahelical oxoG-encounter complexes are compared with sequence-matched structures containing a normal G base in place of an oxoG lesion. Although the protein-DNA interfaces in the matched complexes differ by only two atoms-those that distinguish oxoG from G-their pronounced structural differences indicate that MutM can detect a lesion in DNA even at the earliest stages of encounter. All-atom computer simulations show the pathway by which encounter of the enzyme with the lesion causes extrusion from the DNA duplex, and they elucidate the critical free energy difference between oxoG and G along the extrusion pathway.

PubMed: 20010681
DOI: 10.1038/nature08561

実験手法

X-RAY DIFFRACTION (2.05 Å)