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

Wyatt W. Yue, Viktorija Hozjan, Wei Ge, Christoph Loenarz, Christopher D O Cooper, Christopher J. Schofield, Kathryn L. Kavanagh, Udo Oppermann, Michael A. McDonough

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Crystallographic analysis of the catalytic domain of PHD finger protein 8 (PHF8), an Nε-methyl lysine histone demethylase associated with mental retardation and cleft lip/palate, reveals a double-stranded β-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 Nε-methyl lysine demethylase subfamilies.

LanguageEnglish
Pages825-830
Number of pages6
JournalFEBS Letters
Volume584
Issue number4
DOIs
Publication statusPublished - Feb 2010
Externally publishedYes

Fingerprint

Fingers
Lysine
Crystal structure
Catalytic Domain
Histone Demethylases
Oxygenases
Proteins
Cleft Lip
Cleft Palate
Intellectual Disability
Binding Sites
alpha-ketoglutaric acid

Cite this

Yue, W. W., Hozjan, V., Ge, W., Loenarz, C., Cooper, C. D. O., Schofield, C. J., ... McDonough, M. A. (2010). Crystal structure of the PHF8 Jumonji domain, an Nε-methyl lysine demethylase. FEBS Letters, 584(4), 825-830. https://doi.org/10.1016/j.febslet.2009.12.055
Yue, Wyatt W. ; Hozjan, Viktorija ; Ge, Wei ; Loenarz, Christoph ; Cooper, Christopher D O ; Schofield, Christopher J. ; Kavanagh, Kathryn L. ; Oppermann, Udo ; McDonough, Michael A. / Crystal structure of the PHF8 Jumonji domain, an Nε-methyl lysine demethylase. In: FEBS Letters. 2010 ; Vol. 584, No. 4. pp. 825-830.
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Yue, WW, Hozjan, V, Ge, W, Loenarz, C, Cooper, CDO, Schofield, CJ, Kavanagh, KL, Oppermann, U & McDonough, MA 2010, 'Crystal structure of the PHF8 Jumonji domain, an Nε-methyl lysine demethylase', FEBS Letters, vol. 584, no. 4, pp. 825-830. https://doi.org/10.1016/j.febslet.2009.12.055

Crystal structure of the PHF8 Jumonji domain, an Nε-methyl lysine demethylase. / Yue, Wyatt W.; Hozjan, Viktorija; Ge, Wei; Loenarz, Christoph; Cooper, Christopher D O; Schofield, Christopher J.; Kavanagh, Kathryn L.; Oppermann, Udo; McDonough, Michael A.

In: FEBS Letters, Vol. 584, No. 4, 02.2010, p. 825-830.

Research output: Contribution to journalArticle

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AU - Hozjan, Viktorija

AU - Ge, Wei

AU - Loenarz, Christoph

AU - Cooper, Christopher D O

AU - Schofield, Christopher J.

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