Chemistry Newsblog

Category: In Print

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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Cover featuring the Christov Lab (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.

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Chemistry in Print

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Chemistry Team Publishes in JACS Au

Congratulations to the team including Department of Chemistry Ph.D. students Shobhit Chaturvedi (lead author), Bathir Sathik, and Sodiq Waheed, and undergraduate students Jon Wildey (chemical engineering) and Cait Warner (biological sciences), and led by Christo Christov and Tatyana Karabencheva-Christova (Chem), whose article was published in JACS Au.

The article is titled “Can Second Coordination Sphere and Long-Range Interactions Modulate Hydrogen Atom Transfer in a Non-Heme Fe(II)-Dependent Histone Demethylase?” Christopher Schofield of the University of Oxford, U.K., is also a co-author of the article. This research is supported by NIH grant GM139118.

The study reveals how residues in the second coordination sphere and beyond drive and control the reactivity of the non-heme iron(iv)-oxo complex of the histone demethylase PHF8 to perform the key hydrogen atom abstraction reaction in its catalytic mechanism.

Chemistry Team Publishes in Chemistry – A European Journal

Ph.D. student Sodiq Waheed (chemistry) and Christo Christov (Chem) are participants in a collaborative experimental/computational study led by Nicolai Lehnert at the University of Michigan which was published in Chemistry – A European Journal.

The study, titled “YfeX – A New Platform for Carbene Transferase Development with High Intrinsic Reactivity,” focuses on a redesign of YfeX enzyme as a platform for carbene transferase reactions.

Victor Sosa Alfaro (lead author) and Hannah Palomino of the University of Michigan and Anja Knorrscheidt and Martin Weissenborn of the Martin Luther University of Halle-Wittenberg, Germany, are co-authors of the manuscript.

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In Print

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Christo Z Christov (Chem), chemistry PhD candidate Shobhit Chaturvedi, Rajeev Ramanan, a postdoctoral scholar currently at NIT Rourkela (India), Jian Hu (Michigan State University) and Robert Hausinger (Michigan State University) published an article entitled: “Atomic and Electronic Structure Determinants Distinguish between Ethylene Formation and L-Arginine Hydroxylation Reaction Mechanisms in the Ethylene-Forming Enzyme,” in ACS CATALYSIS. Their article reveals the unique mechanism of the non-heme Fe (II)- and 2-Oxoglutarate (2OG)-dependent Ethylene-Forming Enzyme (EFE).

The study reveals that unique structural rearrangement triggers the splitting of the 2OG co-substrate that leads to the formation of ethylene in EFE in competition of a standard hydroxylation reaction. The study provides a background for increased enzymatic production of ethylene. The research is supported by NSF grants 1904215 and 1904295.

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In Print

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Christina J. Welch, Priyanka D. Kadav, Jared L. Edwards, Jessica Krycia, Melanie L. Talaga, Purnima Bandyopadhyay, and Tarun K. Dam were published on September 3rd, 2020. Their paper, “A Rapid and Facile Purification Method for Glycan‐Binding Proteins and Glycoproteins” was funded by the National Science Foundation. Grant Number: 1608537. It was published on the cover of the September issue of Current Protocols in Protein Science.

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In Print

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Researchers from the Department of Chemistry have revealed the catalytic strategy of a key enzyme for epigenetic regulation. Rajeev Ramanan, a postdoctoral scholar (Chem), currently an assistant professor at NIT Rourkela (India), Shobhit Chaturvedi, a Ph.D. candidate (Chem), Chris Schofield, University of Oxford (UK), Nicolai Lehnert, the University of Michigan, led by Christo Z. Christov (Chem) and Tatyana Karabencheva-Christova (Chem) published an article entitled: “Catalysis By the JmjC Histone Demethylase KDM4A Integrates Substrate Dynamics, Correlated Motions and Molecular Orbital Control” in Chemical Science, the flagship journal of the Royal Society of Chemistry.

The study focuses on a key enzyme for epigenetic regulation — non-heme Fe (II) Histone Demethylase KDM4A and reveals the important catalytic interactions that distinguish KDM4A from other KDMs and its catalytic mechanism with natural and alternative substrates. The research is supported by NSF grant 1904215.

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In Print

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Ph.D. candidate Sodiq Waheed (Chem), postdoctoral scholar Rajeev Ramanan (Chem), Ph.D. candidate Shobhit Chaturvedi (Chem), Tatyana Karabencheva-Christova (Chem) and Christo Christov (Chem) were listed as co-authors in an article titled “Role of Structural Dynamics in Selectivity and Mechanism of Non-heme Fe(II) and 2-Oxoglutarate-Dependent Oxygenases Involved in DNA Repair” published in ACS Central Science.

Chris Schofield of the University of Oxford and Nicolai Lehnert of the University of Michigan were also listed as co-authors on the article.

Led by Karabencheva-Christova and Christov, the research group revealed the vital effect of DNA conformational dynamics on the catalytic mechanism of the bacterial non-heme Fe(II)- and 2-Oxoglutarate-Dependent DNA Demetylase AlkB and the human homolog AlkBH2. The article was also selected for a supplementary cover. 

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