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

Yue, Wyatt W., Hozjan, Viktorija, Ge, Wei, Loenarz, Christoph, Cooper, Christopher D.O., Schofield, Christopher J., Kavanagh, Kathryn L., Oppermann, Udo and McDonough, Michael A. (2010) Crystal structure of the PHF8 Jumonji domain, an Nepsilon-methyl lysine demethylase. FEBS Letters, 584 (4). pp. 825-830. ISSN 0014-5793

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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.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Schools: School of Applied Sciences
Depositing User: Christopher Cooper
Date Deposited: 23 Nov 2015 15:15
Last Modified: 02 Dec 2015 13:14


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