3PU3

PHF2 Jumonji domain-NOG complex

Summary for 3PU3

• Entry DOI: 10.2210/pdb3pu3/pdb
• Related: 3PTR 3PUS 3pu8 3pua
• Descriptor: PHD finger protein 2, N-OXALYLGLYCINE, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: alpha-ketoglutarate-fe2+ dependent dioxygenases, histone tail binding protein, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus, nucleolus: O75151
• Total number of polymer chains: 2
• Total formula weight: 92485.62

Authors

Horton, J.R.,Upadhyay, A.K.,Hashimoto, H.,Zhang, X.,Cheng, X. (deposition date: 2010-12-03, release date: 2011-01-26, Last modification date: 2023-09-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.95 Å)