Crystal structure of the PHF8 Jumonji domain, an Nε‐methyl lysine demethylase
Copyright policy )Crystal structure of the PHF8 Jumonji domain, an Nε‐methyl lysine demethylase
Crystallographic analysis of the catalytic domain of PHD finger protein 8 (PHF8), an N ε‐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 N ε‐methyl lysine demethylase subfamilies.
- University of Oxford United Kingdom
- Structural Genomics Consortium Canada
Models, Molecular, Jumonji Domain-Containing Histone Demethylases, Protein Conformation, Iron, Molecular Sequence Data, chemistry, Crystallography, X-Ray, Transcriptional regulation, Humans, genetics, Amino Acid Sequence, Histone Demethylases, Epigenetic modification, Binding Sites, Sequence Homology, Amino Acid, Histone lysine demethylase, Lysine, 2-Oxoglutarate oxygenase, Protein Structure, Tertiary, JmjC, Mutation, Ketoglutaric Acids, metabolism, Protein Binding, Transcription Factors
Models, Molecular, Jumonji Domain-Containing Histone Demethylases, Protein Conformation, Iron, Molecular Sequence Data, chemistry, Crystallography, X-Ray, Transcriptional regulation, Humans, genetics, Amino Acid Sequence, Histone Demethylases, Epigenetic modification, Binding Sites, Sequence Homology, Amino Acid, Histone lysine demethylase, Lysine, 2-Oxoglutarate oxygenase, Protein Structure, Tertiary, JmjC, Mutation, Ketoglutaric Acids, metabolism, Protein Binding, Transcription Factors
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