2YBS: JMJD2A COMPLEXED WITH S-2-HYDROXYGLUTARATE AND HISTONE H3K36me3 PEPTIDE (30-41)

Citation:
Abstract
Mutations in isocitrate dehydrogenases (IDHs) have a gain-of-function effect leading to R(-)-2-hydroxyglutarate (R-2HG) accumulation. By using biochemical, structural and cellular assays, we show that either or both R- and S-2HG inhibit 2-oxoglutarate (2OG)-dependent oxygenases with varying potencies. Half-maximal inhibitory concentration (IC(50)) values for the R-form of 2HG varied from approximately 25 muM for the histone N(varepsilon)-lysine demethylase JMJD2A to more than 5 mM for the hypoxia-inducible factor (HIF) prolyl hydroxylase. The results indicate that candidate oncogenic pathways in IDH-associated malignancy should include those that are regulated by other 2OG oxygenases than HIF hydroxylases, in particular those involving the regulation of histone methylation.
PDB ID: 2YBSDownload
MMDB ID: 89493
PDB Deposition Date: 2011/3/10
Updated in MMDB: 2011/05
Experimental Method:
x-ray diffraction
Resolution: 2.32  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 2YBS: dimeric; determined by author and by software (PISA)
Molecular Components in 2YBS
Label Count Molecule
Proteins (2 molecules)
1
Lysine-specific Demethylase 4A(Gene symbol: KDM4A)
Molecule annotation
1
Histone H3.1t(Gene symbol: HIST3H3)
Molecule annotation
Chemicals (4 molecules)
1
1
2
1
3
1
4
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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