4CXY

Crystal structure of human FTO in complex with acylhydrazine inhibitor 21

4CXY の概要

• エントリーDOI: 10.2210/pdb4cxy/pdb
• 関連するPDBエントリー: 4CXW 4CXX 4CXZ 4CY0
• 分子名称: ALPHA-KETOGLUTARATE-DEPENDENT DIOXYGENASE FTO, (E)-4-(2-Nicotinoylhydrazinyl)-4-oxobut-2-enoic acid, NICKEL (II) ION, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, small molecular probe
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Nucleus : Q9C0B1
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57175.63

構造登録者

Toh, D.W.,Sun, L.,Tan, J.,Chen, Y.,Lau, L.Z.M.,Hong, W.,Woon, E.C.Y.,Gao, Y.G. (登録日: 2014-04-09, 公開日: 2014-10-01, 最終更新日: 2023-12-20)

主引用文献

Toh, J.D.W.,Sun, L.,Lau, L.Z.M.,Tan, J.,Low, J.J.A.,Tang, C.W.Q.,Cheong, E.J.Y.,Tan, M.J.H.,Chen, Y.,Hong, W.,Gao, Y.G.,Woon, E.C.Y.
A strategy based on nucleotide specificity leads to a subfamily-selective and cell-active inhibitor ofN6-methyladenosine demethylase FTO.
Chem Sci, 6:112-122, 2015

PubMed Abstract: The AlkB family of nucleic acid demethylases are of intense biological and medical interest because of their roles in nucleic acid repair and epigenetic modification. However their functional and molecular mechanisms are unclear, hence, there is strong interest in developing selective inhibitors for them. Here we report the identification of key residues within the nucleotide-binding sites of the AlkB subfamilies that likely determine their substrate specificity. We further provide proof of principle that a strategy exploiting these inherent structural differences can enable selective and potent inhibition of the AlkB subfamilies. This is demonstrated by the first report of a subfamily-selective and cell-active FTO inhibitor . The distinct selectivity of for FTO against other AlkB subfamilies and 2OG oxygenases shall be of considerable interest with regards to its potential use as a functional probe. The strategy outlined here is likely applicable to other AlkB subfamilies, and, more widely, to other 2OG oxygenases.

PubMed: 28553460
DOI: 10.1039/c4sc02554g

実験手法

X-RAY DIFFRACTION (2.65 Å)