3n9o is a 3 chain structure with sequence from Caeel. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
[KDM7_CAEEL] Histone demethylase required for nervous system development. Specifically demethylates dimethylated 'Lys-9' and 'Lys-27' (H3K9me2 and H3K27me2, respectively) of histone H3, thereby playing a central role in histone code.[1][2][3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Histone lysine methylation can be removed by JmjC domain-containing proteins in a sequence- and methylation-state-specific manner. However, how substrate specificity is determined and how the enzymes are regulated were largely unknown. We recently found that ceKDM7A, a PHD- and JmjC domain-containing protein, is a histone demethylase specific for H3K9me2 and H3K27me2, and the PHD finger binding to H3K4me3 guides the demethylation activity in vivo. To provide structural insight into the molecular mechanisms for the enzymatic activity and the function of the PHD finger, we solved six crystal structures of the enzyme in apo form and in complex with single or two peptides containing various combinations of H3K4me3, H3K9me2, and H3K27me2 modifications. The structures indicate that H3K9me2 and H3K27me2 interact with ceKDM7A in a similar fashion, and that the peptide-binding specificity is determined by a network of specific interactions. The geometrical measurement of the structures also revealed that H3K4me3 associated with the PHD finger and H3K9me2 bound to the JmjC domain are from two separate molecules, suggesting a trans-histone peptide-binding mechanism. Thus, our systemic structural studies reveal not only the substrate recognition by the catalytic domain but also more importantly, the molecular mechanism of dual specificity of ceDKM7A for both H3K9me2 and H3K27me2.
Structural insights into a dual-specificity histone demethylase ceKDM7A from Caenorhabditis elegans.,Yang Y, Hu L, Wang P, Hou H, Lin Y, Liu Y, Li Z, Gong R, Feng X, Zhou L, Zhang W, Dong Y, Yang H, Lin H, Wang Y, Chen CD, Xu Y Cell Res. 2010 Aug;20(8):886-98. Epub 2010 Jun 22. PMID:20567261[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
↑Lin H, Wang Y, Wang Y, Tian F, Pu P, Yu Y, Mao H, Yang Y, Wang P, Hu L, Lin Y, Liu Y, Xu Y, Chen CD. Coordinated regulation of active and repressive histone methylations by a dual-specificity histone demethylase ceKDM7A from Caenorhabditis elegans. Cell Res. 2010 Aug;20(8):899-907. doi: 10.1038/cr.2010.84. Epub 2010 Jun 22. PMID:20567262 doi:10.1038/cr.2010.84
↑Kleine-Kohlbrecher D, Christensen J, Vandamme J, Abarrategui I, Bak M, Tommerup N, Shi X, Gozani O, Rappsilber J, Salcini AE, Helin K. A functional link between the histone demethylase PHF8 and the transcription factor ZNF711 in X-linked mental retardation. Mol Cell. 2010 Apr 23;38(2):165-78. doi: 10.1016/j.molcel.2010.03.002. Epub 2010 , Mar 25. PMID:20346720 doi:10.1016/j.molcel.2010.03.002
↑Yang Y, Hu L, Wang P, Hou H, Lin Y, Liu Y, Li Z, Gong R, Feng X, Zhou L, Zhang W, Dong Y, Yang H, Lin H, Wang Y, Chen CD, Xu Y. Structural insights into a dual-specificity histone demethylase ceKDM7A from Caenorhabditis elegans. Cell Res. 2010 Aug;20(8):886-98. Epub 2010 Jun 22. PMID:20567261 doi:10.1038/cr.2010.86
↑Yang Y, Hu L, Wang P, Hou H, Lin Y, Liu Y, Li Z, Gong R, Feng X, Zhou L, Zhang W, Dong Y, Yang H, Lin H, Wang Y, Chen CD, Xu Y. Structural insights into a dual-specificity histone demethylase ceKDM7A from Caenorhabditis elegans. Cell Res. 2010 Aug;20(8):886-98. Epub 2010 Jun 22. PMID:20567261 doi:10.1038/cr.2010.86
