Crystal structure of the PHF8 Jumonji domain, an Nepsilon-methyl lysine demethylase
| Autor: | Viktorija Hozjan, Wyatt W. Yue, Michael A. McDonough, Christopher D.O. Cooper, Udo Oppermann, Christopher J. Schofield, Christoph Loenarz, Wei Ge, Kathryn L. Kavanagh |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular Jumonji Domain-Containing Histone Demethylases Protein Conformation Iron Lysine Molecular Sequence Data Biophysics chemistry Crystallography X-Ray Biochemistry Protein structure Transcriptional regulation Structural Biology Humans genetics Amino Acid Sequence Binding site Molecular Biology Histone Demethylases Epigenetic modification Binding Sites biology Sequence Homology Amino Acid PHF8 Histone lysine demethylase 2-Oxoglutarate oxygenase Cell Biology Protein Structure Tertiary JmjC PHD finger Mutation biology.protein Demethylase Ketoglutaric Acids JARID1B metabolism Protein Binding Transcription Factors |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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