Chemistry Newsblog

Day: November 30, 2023

In Print: Tatyana Karabencheva-Christova Revealing the Catalytic Strategy of FTO

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Diagram of the FTO enzyme catalysis
The FTO enzyme catalyzes the reaction of hydroxylation of 6-methyladenine (m6A) to 6-hydroxymethyl adenine (hm6-A) and then the reaction of oxidation of hm6-A to 6-formyl adenine (f6A). Mutations of the residues in the second coordination sphere influence the activation barrier of the Hydrogen Atom Transfer (HAT) which is the rate-limiting step.

A team from the Department of Chemistry led by Associate Professor Tatyana Karabencheva-Christova and including Ph.D. student Ann Varghese (first author); former Ph.D. students Sodiq Waheed ’23 (Ph.D. Computational Chemistry, currently a researcher at Lilly Corporate Center, Indianapolis) and Shobhit Chaturvedi ’22 (M.S. Ph.D. Chemistry, currently a postdoctoral researcher at UCLA); and undergraduate students Isabella DiCastri, Ciara LaRouche and Brendan Kaski has published an article in Chem Catalysis.

The article is titled “Revealing the catalytic strategy of FTO.” It provides unique insight into the catalytic mechanism of the fat-mass and obesity-associated protein (FTO), which is an Fe(II)- and 2-oxoglutarate (2OG)-dependent oxygenase targeted for treating obesity and cancer. The study reveals that the mutant R316Q, which is related to diseases, slows down the O2 activation and hydrogen atom transfer rates.

Professor Christo Christov (Chem) is a collaborator in this study, along with Nicolai Lehnert of the University of Michigan and Deyu Li of the University of Rhode Island.

The study is funded by the National Institutes of Health grant 2R15GM132873-02.

About the Chemistry Department at Michigan Technological University

Chemists at Michigan Technological University help students apply academic concepts to real-world issues and advance research making contributions to health and well-being, environmental protection, responsible use of materials, and climate stabilization. The Chemistry Department offers five undergraduate degrees, an MS and PhD in Chemistry, and an accelerated MS. Supercharge your chemistry skills to meet the demands of a technology-driven society at a flagship public research university powered by science, technology, engineering, and math. Graduate with the theoretical knowledge and practical experience needed to solve real-world problems and succeed in academia, research, and tomorrow’s high-tech business landscape.

Questions? Contact us at chemistry@mtu.edu. Follow all the latest happenings on the Chemistry Blog.

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In Print: Christo Christov: Catalysis by KDM6 Histone Demethylases – A Synergy between the Non-Heme Iron(II) Center, Second Coordination Sphere, and Long-Range Interactions

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Chemistry A European Journal cover image
Chemistry A European Journal Sept 2023 Cover (by Sarah Atkinson)

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.

About the Chemistry Department at Michigan Tech

Chemists at Michigan Technological University help students apply academic concepts to real-world issues and advance research making contributions to health and well-being, environmental protection, responsible use of materials, and climate stabilization. The Chemistry Department offers five undergraduate degrees, an MS and PhD in Chemistry, and an accelerated MS. Supercharge your chemistry skills to meet the demands of a technology-driven society at a flagship public research university powered by science, technology, engineering, and math. Graduate with the theoretical knowledge and practical experience needed to solve real-world problems and succeed in academia, research, and tomorrow’s high-tech business landscape.

Questions? Contact us at chemistry@mtu.edu. Follow all the latest happenings on the Chemistry Blog.

Continue Reading →