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

33 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.

Original languageEnglish
Pages (from-to)825-830
Number of pages6
JournalFEBS Letters
Volume584
Issue number4
DOIs
Publication statusPublished - Feb 2010
Externally publishedYes

Fingerprint Dive into the research topics of 'Crystal structure of the PHF8 Jumonji domain, an Nε-methyl lysine demethylase'. Together they form a unique fingerprint.

  • Cite this

    Yue, W. W., Hozjan, V., Ge, W., Loenarz, C., Cooper, C. D. O., Schofield, C. J., Kavanagh, K. L., Oppermann, U., & 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