2C53

A comparative study of uracil DNA glycosylases from human and herpes simplex virus type 1

2C53 の概要

• エントリーDOI: 10.2210/pdb2c53/pdb
• 関連するPDBエントリー: 1LAU 1UDG 1UDH 1UDI 2C56
• 分子名称: URACIL DNA GLYCOSYLASE, 2'-DEOXYURIDINE, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: hydrolase, uracil dna glycosylase, dna repair, dna damage, glycosidase
• 由来する生物種: HUMAN HERPESVIRUS 1
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27938.00

構造登録者

Krusong, K.,Carpenter, E.P.,Bellmy, S.R.W.,Savva, R.,Baldwin, G.S. (登録日: 2005-10-25, 公開日: 2005-11-28, 最終更新日: 2024-05-08)

主引用文献

Krusong, K.,Carpenter, E.P.,Bellamy, S.R.W.,Savva, R.,Baldwin, G.S.
A Comparative Study of Uracil-DNA Glycosylases from Human and Herpes Simplex Virus Type 1.
J.Biol.Chem., 281:4983-, 2006

PubMed Abstract: Uracil-DNA glycosylase (UNG) is the key enzyme responsible for initiation of base excision repair. We have used both kinetic and binding assays for comparative analysis of UNG enzymes from humans and herpes simplex virus type 1 (HSV-1). Steady-state fluorescence assays showed that hUNG has a much higher specificity constant (k(cat)/K(m)) compared with the viral enzyme due to a lower K(m). The binding of UNG to DNA was also studied using a catalytically inactive mutant of UNG and non-cleavable substrate analogs (2'-deoxypseudouridine and 2'-alpha-fluoro-2'-deoxyuridine). Equilibrium DNA binding revealed that both human and HSV-1 UNG enzymes bind to abasic DNA and both substrate analogs more weakly than to uracil-containing DNA. Structure determination of HSV-1 D88N/H210N UNG in complex with uracil revealed detailed information on substrate binding. Together, these results suggest that a significant proportion of the binding energy is provided by specific interactions with the target uracil. The kinetic parameters for human UNG indicate that it is likely to have activity against both U.A and U.G mismatches in vivo. Weak binding to abasic DNA also suggests that UNG activity is unlikely to be coupled to the subsequent common steps of base excision repair.

PubMed: 16306042
DOI: 10.1074/JBC.M509137200

実験手法

X-RAY DIFFRACTION (1.8 Å)