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 journalArticlepeer-review

36 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

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