A research team led by Professor Christo Christov (Chem) published the article “Catalysis by KDM6 Histone Demethylases – A Synergy between the Non-Heme Iron(II) Center, Second Coordination Sphere, and Long-Range Interactions,” in Chemistry – A European Journal. The article was selected for a journal cover feature, prepared with the help of Sarah Atkinson.
Many researchers contributed, including Ph.D. student Bathir Jaber Sathik Rifayee (chemistry, the first author); Ph.D. graduate Shobhit Chaturvedi ’22 (M.S. Ph.D. Chemistry, currently a postdoctoral researcher at UCLA); undergraduate students Cait Warner (biological sciences), Jon Wildey (chemical engineering) and Walter White (chemistry); Associate Professor Martin Thompson (Chem); and Professor Christopher Schofield of the University of Oxford, U.K.,
The study revealed the catalytic mechanism of the non-heme Fe(II)/2Oxoglutarate-Dependent histone demethylases from class 6 – KDM6A and KDM6B – enzymes involved in epigenetics regulation and being validated target for drug design. The study revealed the vital role of the second coordination sphere surrounding the non-heme iron center to stabilize the key catalytic species along the catalytic cycle and importantly elucidated the differences in the transition state-stabilization residues between the two enzymes, thus providing background for enzyme-specific drug design.
This research is supported by NIH grant 1R15GM139118.
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