3puq | pdb_00003puq

CEKDM7A from C.Elegans, complex with alpha-KG

Structural highlights

3puq is a 2 chain structure with sequence from Caenorhabditis elegans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	AKG, FE2, GOL, ZN
Related:	3pur
Gene:	F29B9.2 (Caenorhabditis elegans)
Activity:	[Histone_H3-lysine-36_demethylase [Histone H3]-lysine-36 demethylase], with EC number 1.14.11.27
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[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]

Publication Abstract from PubMed

IDH1 and IDH2 mutations occur frequently in gliomas and acute myeloid leukemia, leading to simultaneous loss and gain of activities in the production of alpha-ketoglutarate (alpha-KG) and 2-hydroxyglutarate (2-HG), respectively. Here we demonstrate that 2-HG is a competitive inhibitor of multiple alpha-KG-dependent dioxygenases, including histone demethylases and the TET family of 5-methlycytosine (5mC) hydroxylases. 2-HG occupies the same space as alpha-KG does in the active site of histone demethylases. Ectopic expression of tumor-derived IDH1 and IDH2 mutants inhibits histone demethylation and 5mC hydroxylation. In glioma, IDH1 mutations are associated with increased histone methylation and decreased 5-hydroxylmethylcytosine (5hmC). Hence, tumor-derived IDH1 and IDH2 mutations reduce alpha-KG and accumulate an alpha-KG antagonist, 2-HG, leading to genome-wide histone and DNA methylation alterations.

Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases.,Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, Ito S, Yang C, Wang P, Xiao MT, Liu LX, Jiang WQ, Liu J, Zhang JY, Wang B, Frye S, Zhang Y, Xu YH, Lei QY, Guan KL, Zhao SM, Xiong Y Cancer Cell. 2011 Jan 18;19(1):17-30. PMID:21251613^[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
↑ Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, Ito S, Yang C, Wang P, Xiao MT, Liu LX, Jiang WQ, Liu J, Zhang JY, Wang B, Frye S, Zhang Y, Xu YH, Lei QY, Guan KL, Zhao SM, Xiong Y. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011 Jan 18;19(1):17-30. PMID:21251613 doi:10.1016/j.ccr.2010.12.014

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] 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

[4] Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, Ito S, Yang C, Wang P, Xiao MT, Liu LX, Jiang WQ, Liu J, Zhang JY, Wang B, Frye S, Zhang Y, Xu YH, Lei QY, Guan KL, Zhao SM, Xiong Y. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011 Jan 18;19(1):17-30. PMID:21251613 doi:10.1016/j.ccr.2010.12.014

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3puq | pdb_00003puq

CEKDM7A from C.Elegans, complex with alpha-KG

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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