Chemistry Newsblog

Category: In Print

In Print: Christov Published in ACS Journal Biochemistry

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A team from the Department of Chemistry at Michigan Technological University has published an article in the American Chemical Society (ACS) journal Biochemistry.

The MTU team is led by Christo Z. Christov and includes Ph.D. students Midhun G. Thomas and Simahudeen Bathir J.S. Rifayee. In addition, a team of Michigan State University researchers including Shramana Chatterjee, Mathia Fellner, and Joel Rankin, led by Jian Hu and Robert Hausinger, are collaborators in this study.

Christov ACS Biochemistry
Christo Z. Christov
Professor of Chemistry
Midhun Thomas ACS Journal Biochemistry
Midhun G. Thomas
Ph.D. student of Chemistry
Bathir ACS Biochemistry
Simahudeen Bathir J.S. Rifayee
Ph.D. student of Chemistry

The article is titled “Structural, Spectroscopic, and Computational Insights from Canavanine-Bound and Two Catalytically Compromised Variants of the Ethylene-Forming Enzyme.” This study on the Fe(II)/2-oxoglutarate-dependent ethylene-forming enzyme (EFE) reveals how the change of key residues in the second coordination sphere and the binding of alternative substrates influence the EFE’s structure-function relationships and can be used for increasing the ethylene production.

The research is supported by NSF grants 1904215 and 2203630 to C.Z.C. and 1904295 and 2203472 to R.P.H. and J.H.”

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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Karabencheva-Christova Lab Reveals Molecular Mechanism of Cancer-Associated Enzyme

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Cover page and images of Karabencheva-Christova's New Study
Karabencheva-Christova Publishes New Study
Tatyana Karabencheva-Christova
Associate Professor

A recent research article by Karabencheva-Christova’s group was showcased on the back cover of Chemical Science, the flagship journal of the Royal Society of Chemistry (RSC).

The team led by Dr. Karabencheva-Christova includes Ph.D. students Anandhu Krisnan (first author) and Fathima Hameed Cherilakkudy; Ph.D. graduate Sodiq Waheed ’23, currently a researcher at Eli Lilly in Indianapolis, Indiana; and Ph.D. graduate Ann Varghese ’23, currently a postdoctoral researcher at the National Center for Toxicological Research, Food and Drug Administration (FDA), in Jefferson, Arkansas. Professor Christopher J. Schofield from the University of Oxford, U.K., was a collaborator on the study.

The research illuminates the origin of the atypical catalytic strategy employed by the human non-heme Fe(II)/2-oxoglutarate-dependent dioxygenase AspH, which is a target for anticancer therapy.
This research was funded by NIH grant 2R15GM132873-02. We thank Sarah Atkinson (RD, MTU) for her assistance with image preparation.

Anandhu Krisnan, Karabencheva-Christova New Study
Anandhu Krisnan
Ph.D. student
Fathima Hameed Cherilakkudy, Karabencheva-Christova New Study
Fathima Hameed Cherilakkudy
PhD Student
Ann Varghese ’23
Ann Varghese ’23
Ph.D. graduate
Sodiq Waheed ’23
Sodiq Waheed ’23
Ph.D. graduate

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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In Print: Collaborative Cancer Research Published

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Cover page of the journal on Cancer Research
Cover Page of the Journal of Materials Chemistry B

A team of dedicated researchers achieved a significant milestone in the field of cancer detection and monitoring. Their collaborative cancer research culminated in the publication of a paper in the prestigious Journal of Materials Chemistry B.

Collaboration Across Departments

The team was led by Ph.D. student Dilka Liyana Arachchige, alongside Research Scientist Sushil K. Dwivedi (Chem); undergraduate students May Waters, Sophia Jaeger, Joe Peters, Daniel R. Tucker and Micaela Geborkoff; and Professors Thomas Werner (Biological Sciences) and Rudy L. Luck and Haiying Liu (both Chemistry).

Their groundbreaking paper is titled “Sensitive monitoring of NAD(P)H levels within cancer cells using mitochondria-targeted near-infrared cyanine dyes with optimized electron-withdrawing acceptors.”

Cancer Research Featured on the Cover

Highlighted on the journal’s front cover, the research introduces two cutting-edge near-infrared cyanine dyes meticulously engineered for the precise detection of NAD(P)H, a critical biomarker in cancer metabolism. These dyes exhibit primary absorption peaks at 438 nm and 470 nm, transitioning seamlessly into fluorescence at 748 nm and 730 nm upon interaction with NAD(P)H, showcasing an unprecedented level of sensitivity. Notably, their unique design enables deep tissue penetration with minimal disruption, rendering them invaluable for non-invasive cancer detection and continuous monitoring.

Of particular significance is their efficacy in monitoring glycolysis-induced NAD(P)H levels within mitochondria, offering insights into cancer cell metabolism and the effects of chemotherapy drugs. This breakthrough promises to advance our understanding of cancer progression and enhance treatment strategies.

 Key Funding Agencies Support Collaborative Cancer Research

The research, supported by the National Institute of General Medical Sciences and the National Institutes of Health under multiple award numbers, underscores the vital role of funding agencies in driving scientific innovation. Liu, expressing gratitude as a co-PI, acknowledges the National Science Foundation’s support for a new NMR spectrometer, emphasizing the collaborative effort across disciplines in pushing the boundaries of scientific discovery.

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: Karabencheva-Christova featured in the the Journal of Physical Chemistry B

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Tatyana G. Karabencheva-Christova
Dr. Karabencheva-Christova

A team from the Department of Chemistry, led by Associate Professor Tatyana Karabencheva-Christova and including Ph.D. student Ann Varghese (first author); Sodiq Waheed ’23 (Ph.D. Computational Chemistry, currently a researcher at Eli Lilly in Indianapolis, Indiana); postdoctoral researcher Koteswararao Gorantla; and undergraduate students Isabella DiCastri, Ciara LaRouche and Brendan Kaski, has published an article in the Journal of Physical Chemistry B.

The article is titled “Catalytic Mechanism of Collagen Hydrolysis by Zinc(II)-Dependent Matrix Metalloproteinase-1”

Professor Gregg Fields from Florida Atlantic University is a collaborator in this study.

The study reveals the catalytic mechanism of collagen hydrolysis by matrix metalloproteinase-1 (MMP-1), an extensive target for drug design, for the first time via a multilevel computational chemistry approach. The article was featured as a supplementary cover. The authors thank Sarah Atkinson (RD) for assisting with cover image preparation. The study is funded by NIH 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: 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.

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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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