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Crystal structure of the PHF8 Jumonji domain, an Nepsilon-methyl lysine demethylase
DOI:
10.1016/j.febslet.2009.12.055
PMID:
20067792
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)