Inhibition of the histone lysine demethylase JMJD2A by ejection of structural Zn(II).
JMJD2A, a 2-oxoglutarate dependent N(epsilon)-methyl lysine histone demethylase, is inhibited by disruption of its Zn-binding site by Zn-ejecting compounds including disulfiram and ebselen; this observation may enable the development of inhibitors selective for this subfamily of 2OG dependent oxygenases that do not rely on binding to the highly-conserved Fe(ii)-containing active site.
Sekirnik
Rok
R
Department of Chemistry and the Oxford Centre for Integrative Systems Biology, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, UK OX1 3TA.
Rose
Nathan R
NR
Thalhammer
Armin
A
Seden
Peter T
PT
Mecinović
Jasmin
J
Schofield
Christopher J
CJ
D001393:Azoles / Q000737:chemistry; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004221:Disulfiram / Q000737:chemistry; D054833:Isoindoles; D056484:Jumonji Domain-Containing Histone Demethylases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016566:Organoselenium Compounds / Q000737:chemistry; D012643:Selenium / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D015032:Zinc / Q000737:chemistry*
D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D056484:Jumonji Domain-Containing Histone Demethylases; D012643:Selenium; D015032:Zinc; D004221:Disulfiram