3PU8

PHF2 Jumonji-NOG-Fe(II) complex

3PU8 の概要

• エントリーDOI: 10.2210/pdb3pu8/pdb
• 関連するPDBエントリー: 3PTR 3PU3 3PUA 3PUS
• 分子名称: PHD finger protein 2, OXYGEN MOLECULE, 1,2-ETHANEDIOL, ... (8 entities in total)
• 機能のキーワード: alpha-ketoglutarate-fe2+ dependent dioxygenases, histone tail binding protein, protein binding
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus, nucleolus: O75151
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 91472.67

構造登録者

Horton, J.R.,Upadhyay, A.K.,Hashimoto, H.,Zhang, X.,Cheng, X. (登録日: 2010-12-03, 公開日: 2011-01-26, 最終更新日: 2023-09-06)

主引用文献

Horton, J.R.,Upadhyay, A.K.,Hashimoto, H.,Zhang, X.,Cheng, X.
Structural basis for human PHF2 Jumonji domain interaction with metal ions.
J.Mol.Biol., 406:1-8, 2011

PubMed Abstract: PHF2 belongs to a class of α-ketoglutarate-Fe(2)(+)-dependent dioxygenases. PHF2 harbors a plant homeodomain (PHD) and a Jumonji domain. PHF2, via its PHD, binds Lys4-trimethylated histone 3 in submicromolar affinity and has been reported to have the demethylase activity of monomethylated lysine 9 of histone 3 in vivo. However, we did not detect demethylase activity for PHF2 Jumonji domain (with and without its linked PHD) in the context of histone peptides. We determined the crystal structures of PHF2 Jumonji domain in the absence and presence of additional exogenous metal ions. When Fe(2+) or Ni(2+) was added at a high concentration (50 mM) and allowed to soak in the preformed crystals, Fe(2+) or Ni(2+) was bound by six ligands in an octahedral coordination. The side chains of H249 and D251 and the two oxygen atoms of N-oxalylglycine (an analog of α-ketoglutarate) provide four coordinations in the equatorial plane, while the hydroxyl oxygen atom of Y321 and one water molecule provide the two axial coordinations as the fifth and sixth ligands, respectively. The metal binding site in PHF2 closely resembles the Fe(2+) sites in other Jumonji domains examined, with one important difference-a tyrosine (Y321 of PHF2) replaces histidine as the fifth ligand. However, neither Y321H mutation nor high metal concentration renders PHF2 an active demethylase on histone peptides. Wild type and Y321H mutant bind Ni(2+) with an approximately equal affinity of 50 μM. We propose that there must be other regulatory factors required for the enzymatic activity of PHF2 in vivo or that perhaps PHF2 acts on non-histone substrates. Furthermore, PHF2 shares significant sequence homology throughout the entire region, including the above-mentioned tyrosine at the corresponding iron-binding position, with that of Schizosaccharomyces pombe Epe1, which plays an essential role in heterochromatin function but has no known enzymatic activity.

PubMed: 21167174
DOI: 10.1016/j.jmb.2010.12.013

実験手法

X-RAY DIFFRACTION (1.943 Å)