Crystal structures histone demethylases

It has been shown that JHDMIA demethylates only mono- and dimethyl lysine of histone H3 (H3K36). This was rather unexpected given that the catalytic mechanism of a Jmj C domain does not require a protonated nitrogen, unlike LS D1, and therefore could also have the ability to remove the methyl in all three states. So far, two crystal structures have been deposited in the protein database but without any publication underlining the work. The crystal structures describe two forms of the human JHDMIA lysine demethylase, apo and in a complex with a-ketoglutarate (PDB codes 2yul and 2yu2). 

Chen, Y, Yang, Y, Wang, F., Wan, K., Yamane, K., Zhang, Y. and Lei, M. (2006) Crystal structure ofhuman histone lysine-specific demethylase 1 (LSDl). Proceedings of the National Academy of Sciences of the United States of America, 103 (38), 13956-13961. 

Mimasu, S., Sengoku, T, Fukuzawa, S., Umehara, T. and Yokoyama, S. (2008) Crystal structure of histone demethylase LSDl and tranylcypromine at 2.25 A. Biochemical and Biophysical Research Communications, 366 (1), 15-22. 

Figure 5.13 Histone demethylases. Structures and mechanisms are illustrated for the two subclasses of histone lysine demethylases. (a) Views from an X-ray crystal structure of LSDl (PDB ID 2V1D) in complex with cofactor FAD and a peptide substrate analogue, where methionine replaces methylated lysine, and outline mechanism of the LSDl-catalysed demethylation reaction, (b) Views from an X-ray crystal structure of JMJD2A (PDB ID 20Q6) in complex with co-factor analogue N-oxa-lylglycine and histone substrate trimethylated at H3K9 (note that Ni(II) replaces Fe(II) for crystallography), and outline mechanism of JmjC-domain catalysed lysine demethylation. (c) Representative inhibitors of LSDl and JmjC-domain demethylases.

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