PDBsum entry: 2wwu

Metal-binding protein

PDB id: 2wwu

Contents

Protein chain

363 a.a. *

Ligands

SO4 ×7

ACT ×5

BGC ×2

Metals

_NI

Waters ×168

* Residue conservation analysis

PDB id:

2wwu

Name:

Metal-binding protein

Title:

Crystal structure of the catalytic domain of phd finger protein 8

Structure:

Phd finger protein 8. Chain: a. Fragment: catalytic domain, residues 115-483. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_cell_line: r3-prare2.

Resolution:

2.15Å R-factor: 0.177 R-free: 0.211

Authors:

W.W.Yue,V.Hozjan,C.Cooper,A.Tumber,T.Krojer,J.Muniz, C.Allerston,E.Salah,M.A.Mcdonough,F.Vondelft,C.Arrowsmith, J.Weigelt,A.Edwards,C.Bountra,C.J.Schofield,K.L.Kavanagh, U.Oppermann

Key ref:

W.W.Yue et al. (2010). Crystal structure of the PHF8 Jumonji domain, an Nepsilon-methyl lysine demethylase. Febs Lett, 584, 825-830. PubMed id: 20067792 DOI: 10.1016/j.febslet.2009.12.055

Date:

29-Oct-09 Release date: 17-Nov-09

Protein chain

Q9UPP1  (PHF8_HUMAN) -  Histone lysine demethylase PHF8

Seq: 1060 a.a.

Struc: 363 a.a.

Enzyme reactions

• Enzyme class: E.C.1.14.11.27 - [Histone H3]-lysine-36 demethylase.
• Reaction:
  1. Protein N₆,N₆-dimethyl-L-lysine + 2-oxoglutarate + O₂ = protein N₆-methyl-L-lysine + succinate + formaldehyde + CO₂
  2. Protein N₆-methyl-L-lysine + 2-oxoglutarate + O₂ = protein L-lysine + succinate + formaldehyde + CO₂

Protein N(6),N(6)-dimethyl-L-lysine + 2-oxoglutarate (Bound ligand (Het Group name = BGC) matches with 57.00% similarity) + O(2) = protein N(6)-methyl-L-lysine + succinate + formaldehyde + CO(2) (Bound ligand (Het Group name = ACT) matches with 75.00% similarity)

Protein N(6)-methyl-L-lysine + 2-oxoglutarate (Bound ligand (Het Group name = BGC) matches with 57.00% similarity) + O(2) = protein L-lysine + succinate + formaldehyde + CO(2) (Bound ligand (Het Group name = ACT) matches with 75.00% similarity)

• Cofactor: Fe(2+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.febslet.2009.12.055

Febs Lett 584:825-830 (2010)

PubMed id: 20067792

Crystal structure of the PHF8 Jumonji domain, an Nepsilon-methyl lysine demethylase.

W.W.Yue, V.Hozjan, W.Ge, C.Loenarz, C.D.Cooper, C.J.Schofield, K.L.Kavanagh, U.Oppermann, M.A.McDonough.

ABSTRACT

Crystallographic analysis of the catalytic domain of PHD finger protein 8 (PHF8), an N(epsilon)-methyl lysine histone demethylase associated with mental retardation and cleft lip/palate, reveals a double-stranded beta-helix fold with conserved Fe(II) and cosubstrate binding sites typical of the 2-oxoglutarate dependent oxygenases. The PHF8 active site is highly conserved with those of the FBXL10/11demethylases, which are also selective for the di-/mono-methylated lysine states, but differs from that of the JMJD2 demethylases which are selective for tri-/di-methylated states. The results rationalize the lack of activity for the clinically observed F279S PHF8 variant and they will help to identify inhibitors selective for specific N(epsilon)-methyl lysine demethylase subfamilies.