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

DOI: 10.1016/j.febslet.2009.12.055 DOI Help
PMID: 20067792 PMID Help

Authors: Wyatt W. Yue (Structural Genomics Consortium, University of Oxford) , Victoria Hozjan (Structural Genomics Consortium, University of Oxford) , Christoph Leonarz (University of Oxford) , Wei Ge (University of Oxford) , Christopher D. O. Cooper (Structural Genomics Consortium, University of Oxford) , Kathryn L. Kavanagh (Structural Genomics Consortium, University of Oxford) , Udo Oppermann (Structural Genomics Consortium, University of Oxford; Oxford Biomedical Research Unit) , Michael Mcdonough (University of Oxford) , Christoph Loenarz (University of Oxford) , Christopher J. Schofield (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Febs Letters

State: Published (Approved)
Published: February 2010
Diamond Proposal Number(s): 442

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.

Journal Keywords: Binding; Crystallography; X-Ray; Histone; Humans; Iron; Jumonji; Ketoglutaric; Lysine; Models; Molecular; Mutation; Protein; Tertiary; Sequence; Amino; Transcription Factors

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography

Added On: 05/05/2010 10:38

Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)