5VHV

Pseudomonas fluorescens alkylpurine DNA glycosylase AlkC bound to DNA containing an oxocarbenium-intermediate analog

5VHV の概要

• エントリーDOI: 10.2210/pdb5vhv/pdb
• 関連するPDBエントリー: 5VI0
• 分子名称: alkylpurine DNA glycosylase AlkC, DNA (5'-D(*TP*GP*TP*CP*CP*AP*(NRI)P*GP*TP*CP*T)-3'), DNA (5'-D(*AP*AP*GP*AP*CP*TP*TP*GP*GP*AP*C)-3'), ... (8 entities in total)
• 機能のキーワード: dna alkylation repair enzyme, hydrolase-dna complex, hydrolase/dna
• 由来する生物種: Pseudomonas fluorescens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 95892.70

構造登録者

Shi, R.,Eichman, B.F. (登録日: 2017-04-13, 公開日: 2017-10-25, 最終更新日: 2023-10-04)

主引用文献

Shi, R.,Mullins, E.A.,Shen, X.X.,Lay, K.T.,Yuen, P.K.,David, S.S.,Rokas, A.,Eichman, B.F.
Selective base excision repair of DNA damage by the non-base-flipping DNA glycosylase AlkC.
EMBO J., 37:63-74, 2018

PubMed Abstract: DNA glycosylases preserve genome integrity and define the specificity of the base excision repair pathway for discreet, detrimental modifications, and thus, the mechanisms by which glycosylases locate DNA damage are of particular interest. Bacterial AlkC and AlkD are specific for cationic alkylated nucleobases and have a distinctive HEAT-like repeat (HLR) fold. AlkD uses a unique non-base-flipping mechanism that enables excision of bulky lesions more commonly associated with nucleotide excision repair. In contrast, AlkC has a much narrower specificity for small lesions, principally N3-methyladenine (3mA). Here, we describe how AlkC selects for and excises 3mA using a non-base-flipping strategy distinct from that of AlkD. A crystal structure resembling a catalytic intermediate complex shows how AlkC uses unique HLR and immunoglobulin-like domains to induce a sharp kink in the DNA, exposing the damaged nucleobase to active site residues that project into the DNA This active site can accommodate and excise N3-methylcytosine (3mC) and N1-methyladenine (1mA), which are also repaired by AlkB-catalyzed oxidative demethylation, providing a potential alternative mechanism for repair of these lesions in bacteria.

PubMed: 29054852
DOI: 10.15252/embj.201797833

実験手法

X-RAY DIFFRACTION (1.799 Å)