3K3N

Crystal structure of the catalytic core domain of human PHF8

Summary for 3K3N

• Entry DOI: 10.2210/pdb3k3n/pdb
• Related: 3K3O
• Descriptor: PHD finger protein 8, FE (II) ION (3 entities in total)
• Functional Keywords: phf8 (phd finger protein 8), histone demethylase, chromatin modification, methylated h3k9, mental retardation, metal-binding, phosphoprotein, zinc-finger, oxidoreductase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 43335.19

Authors

Yu, L.,Wang, Y.,Huang, S.,Wang, J.,Deng, Z.,Wu, W.,Gong, W.,Chen, Z. (deposition date: 2009-10-03, release date: 2010-01-19, Last modification date: 2023-11-01)

Primary citation

Yu, L.,Wang, Y.,Huang, S.,Wang, J.,Deng, Z.,Zhang, Q.,Wu, W.,Zhang, X.,Liu, Z.,Gong, W.,Chen, Z.
Structural insights into a novel histone demethylase PHF8
Cell Res., 20:166-173, 2010

PubMed Abstract: Dynamic regulation of histone methylation/demethylation plays an important role during development. Mutations and truncations in human plant homeodomain (PHD) finger protein 8 (PHF8) are associated with X-linked mental retardation and facial anomalies, such as a long face, broad nasal tip, cleft lip/cleft palate and large hands, yet its molecular function and structural basis remain unclear. Here, we report the crystal structures of the catalytic core of PHF8 with or without alpha-ketoglutarate (alpha-KG) at high resolution. Biochemical and structural studies reveal that PHF8 is a novel histone demethylase specific for di- and mono-methylated histone H3 lysine 9 (H3K9me2/1), but not for H3K9me3. Our analyses also reveal how human PHF8 discriminates between methylation states and achieves sequence specificity for methylated H3K9. The in vitro demethylation assay also showed that the F279S mutant observed in clinical patients possesses no demethylation activity, suggesting that loss of enzymatic activity is crucial for pathogenesis of PHF8 patients. Taken together, these results will shed light on the molecular mechanism underlying PHF8-associated developmental and neurological diseases.

PubMed: 20101266
DOI: 10.1038/cr.2010.8

Experimental method

X-RAY DIFFRACTION (2.4 Å)