4OCT

Crystal structure of human ALKBH5 crystallized in the presence of Mn^{2+} and 2-oxoglutarate

4OCT の概要

• エントリーDOI: 10.2210/pdb4oct/pdb
• 分子名称: RNA demethylase ALKBH5, MANGANESE (II) ION, 2-OXOGLUTARIC ACID, ... (5 entities in total)
• 機能のキーワード: structural genomics, structural genomics consortium, sgc, rna demethylase, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus speckle : Q6P6C2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51080.09

構造登録者

Tempel, W.,Chao, X.,Liu, K.,Dong, A.,Cerovina, T.,He, H.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.M.,Min, J.,Structural Genomics Consortium (SGC) (登録日: 2014-01-09, 公開日: 2014-04-16, 最終更新日: 2024-11-20)

主引用文献

Xu, C.,Liu, K.,Tempel, W.,Demetriades, M.,Aik, W.,Schofield, C.J.,Min, J.
Structures of human ALKBH5 demethylase reveal a unique binding mode for specific single-stranded N6-methyladenosine RNA demethylation.
J.Biol.Chem., 289:17299-17311, 2014

PubMed Abstract: N(6)-Methyladenosine (m(6)A) is the most prevalent internal RNA modification in eukaryotes. ALKBH5 belongs to the AlkB family of dioxygenases and has been shown to specifically demethylate m(6)A in single-stranded RNA. Here we report crystal structures of ALKBH5 in the presence of either its cofactors or the ALKBH5 inhibitor citrate. Catalytic assays demonstrate that the ALKBH5 catalytic domain can demethylate both single-stranded RNA and single-stranded DNA. We identify the TCA cycle intermediate citrate as a modest inhibitor of ALKHB5 (IC50, ∼488 μm). The structural analysis reveals that a loop region of ALKBH5 is immobilized by a disulfide bond that apparently excludes the binding of dsDNA to ALKBH5. We identify the m(6)A binding pocket of ALKBH5 and the key residues involved in m(6)A recognition using mutagenesis and ITC binding experiments.

PubMed: 24778178
DOI: 10.1074/jbc.M114.550350

実験手法

X-RAY DIFFRACTION (2.28 Å)