3T3Y

Crystal structure of AlkB in complex with Fe(III) and 2-(3-hydroxypicolinomido)acetic acid

3T3Y の概要

• エントリーDOI: 10.2210/pdb3t3y/pdb
• 関連するPDBエントリー: 2FD8 2FDF 2FDG 2FDH 2FDI 2FDJ 2FDK 3BI3 3BIE 3BKZ 3H8O 3H8R 3H8X 3I2O 3I3M 3I3Q 3I49 3KHB 3KHC 3O1M 3O1O 3O1P 3O1R 3O1S 3O1T 3O1U 3O1V 3T4H 3T4V
• 分子名称: Alpha-ketoglutarate-dependent dioxygenase AlkB, FE (III) ION, N-[(3-hydroxypyridin-2-yl)carbonyl]glycine, ... (4 entities in total)
• 機能のキーワード: double-stranded beta-helix, nucleic acid demethylase, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23197.24

構造登録者

Aik, W.S.,McDonough, M.A.,Schofield, C.J. (登録日: 2011-07-25, 公開日: 2012-03-07, 最終更新日: 2023-09-13)

主引用文献

Woon, E.C.,Demetriades, M.,Bagg, E.A.,Aik, W.,Krylova, S.M.,Ma, J.H.,Chan, M.,Walport, L.J.,Wegman, D.W.,Dack, K.N.,McDonough, M.A.,Krylov, S.N.,Schofield, C.J.
Dynamic combinatorial mass spectrometry leads to inhibitors of a 2-oxoglutarate-dependent nucleic Acid demethylase.
J.Med.Chem., 55:2173-2184, 2012

PubMed Abstract: 2-Oxoglutarate-dependent nucleic acid demethylases are of biological interest because of their roles in nucleic acid repair and modification. Although some of these enzymes are linked to physiology, their regulatory roles are unclear. Hence, there is a desire to develop selective inhibitors for them; we report studies on AlkB, which reveal it as being amenable to selective inhibition by small molecules. Dynamic combinatorial chemistry linked to mass spectrometric analyses (DCMS) led to the identification of lead compounds, one of which was analyzed by crystallography. Subsequent structure-guided studies led to the identification of inhibitors of improved potency, some of which were shown to be selective over two other 2OG oxygenases. The work further validates the use of the DCMS method and will help to enable the development of inhibitors of nucleic acid modifying 2OG oxygenases both for use as functional probes and, in the longer term, for potential therapeutic use.

PubMed: 22263962
DOI: 10.1021/jm201417e

実験手法

X-RAY DIFFRACTION (2.001 Å)