5X3G

The WT UNG crystal structure from Nitratifractor salsuginis

5X3G の概要

• エントリーDOI: 10.2210/pdb5x3g/pdb
• 関連するPDBエントリー: 5X3H
• 分子名称: Uracil-DNA glycosylase (2 entities in total)
• 機能のキーワード: uracil dna glycosylase, base excision repair, single-wavelength anomalous dispersion, dna binding protein
• 由来する生物種: Nitratifractor salsuginis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30833.29

構造登録者

Xie, W.,Cao, W.,Chen, R.,Zhang, Z. (登録日: 2017-02-06, 公開日: 2017-10-18, 最終更新日: 2017-12-13)

主引用文献

Li, J.,Chen, R.,Yang, Y.,Zhang, Z.,Fang, G.C.,Xie, W.,Cao, W.
An unconventional family 1 uracil DNA glycosylase in Nitratifractor salsuginis.
FEBS J., 284:4017-4034, 2017

PubMed Abstract: The uracil DNA glycosylase superfamily consists of at least six families with a diverse specificity toward DNA base damage. Family 1 uracil N-glycosylase (UNG) exhibits exclusive specificity on uracil-containing DNA. Here, we report a family 1 UNG homolog from Nitratifractor salsuginis with distinct biochemical features that differentiate it from conventional family 1 UNGs. Globally, the crystal structure of N. salsuginisUNG shows a few additional secondary structural elements. Biochemical and enzyme kinetic analysis, coupled with structural determination, molecular modeling, and molecular dynamics simulations, shows that N. salsuginisUNG contains a salt bridge network that plays an important role in DNA backbone interactions. Disruption of the amino acid residues involved in the salt bridges greatly impedes the enzymatic activity. A tyrosine residue in motif 1 (GQDPY) is one of the distinct sequence features setting family 1 UNG apart from other families. The crystal structure of Y81G mutant indicates that several subtle changes may account for its inactivity. Unlike the conventional family 1 UNG enzymes, N. salsuginisUNG is not inhibited by Ugi, a potent inhibitor specific for family 1 UNG. This study underscores the diversity of paths that a uracil DNA glycosylase may take to acquire its unique structural and biochemical properties during evolution.

PubMed: 28977725
DOI: 10.1111/febs.14285

実験手法

X-RAY DIFFRACTION (2.021 Å)