Seminar

Chemistry’s own Dr. Christo Z. Christov will be our seminar speaker this Friday (October 30th). The virtual seminar will be held via Zoom at 3:00 PM. The passcode is 859189 if needed.

Computational Insight into Catalytic Mechanisms of Non-Heme Fe(II)- and 2-Oxoglutarate-Dependent Oxygenases

Abstract: “Mononuclear non-heme Fe(II) and 2-oxoglutarate (2OG)-dependent enzymes catalyze an incredibly diverse arsenal of chemical reactions with vital biological roles, making them attractive targets for therapeutics and biotechnology developments. Some of the chemical transformations performed by this family of enzymes include hydroxylation, demethylation, desaturation, and cyclization. One of the essential reactions performed by non-heme iron enzymes is histone demethylation. The class of enzymes responsible for histone lysine demethylation is called Histone Lysine Demethylases (KDMs). These enzymes couple decarboxylation of 2OG with substrate oxidation. Important demethylation reactions are catalyzed also by DNA demethylases such as the bacterial AlkB and its human homolog AlkBH2 in single-stranded (ss)- and double-stranded (ds) DNA. Also, an unusual enzymatic transformation performed by the Ethylene-Forming Enzyme (EFE) on its co-substrate (2OG) produces ethylene.”

“In this talk, I will present how applying state-of-the-art computational chemistry methods such as molecular dynamics (MD) and Combined Quantum Mechanical/Molecular Mechanical (QM/MM) we provide a mechanistic insight that cannot be received experimentally. The discussion will focus on: i) the histone demethylases PHF8 (KDM7B) and KDM4A (JMJD2A), which differ in their substrate specificity and domain organization; ii) DNA demethylases AlkB and AlkBH2 that differ in their preference to ss- or ds DNA; and iii) the Ethylene-Forming Enzyme (EFE) that performs a unique transformation of 2OG leading to the production of ethylene. The atomic and molecular orbital interactions along the reaction process within the enzyme environment will be discussed. The studies emphasize the critical importance of the protein environment and dynamics, especially focusing on the second sphere’s interactions and beyond for the catalytic process. The outcomes contribute to a fundamental understanding of enzyme mechanisms and have a long-term impact on enzyme engineering and drug design.”

Bio: Dr. Christo Z. Christov grew up in the town of Sevlievo, Bulgaria. He received MSc in Biochemistry at the University of Sofia, Sofia, and a Ph.D. in Theoretical Chemistry at the Bulgarian Academy of Sciences, Sofia, Bulgaria. Following postdoctoral studies in Spain and the UK, Christo gained a tenured faculty position at the Department of Applied Sciences at Northumbria University, UK in 2010. He was awarded a Fulbright Senior Grant and a Marie Curie International Outgoing Career Development Fellowship for the Department of Chemistry (The Solomon Lab) at Stanford University (2010-2013). Since 2017 Christo is an Associate Professor of Chemistry at the Department of Chemistry at Michigan Technological University, Houghton MI. Christo’s Research interests are in Computational Bioinorganic Chemistry with a focus on non- heme Fe(II) and 2OG-Dependent Oxygenase such as Histone Demethylases and TET enzymes involved in the epigenetic regulation and the Ethylene Forming Enzyme. Currently, Christo’s research is supported by the National Science Foundation of USA.

Virtual Poster Session

The Chemistry Department will be hosting a Virtual Poster Session on Friday, October 23rd, from 3:00-5:00 PM via Zoom. Passcode: 587532 if needed. To smoothly move from one break room to the other, all participants are asked to use Zoom version 5.3.1 or newer.

The goal of the event is to provide undergraduate and graduate students in Chemistry with an opportunity to share their research experiences not only with the Chemistry Department but also with the wider Michigan Tech community and, possibly, with members of the external audience too. You can find the public Canvas course that is hosting this event here:  https://mtu.instructure.com/courses/1336145.

Seminar

We welcome Dr. Christopher N. Bowman as our second seminar speaker of the year! You can join us in learning at 3:00 p.m., via Zoom.

Dr. Bowman will be presenting his piece on “Smart, Responsive Polymers Based on Covalent Adaptable Networks: Photoactivatable Dynamic Covalent Chemistry and Its Applications in Polymer Networks.”

Abstract: Polymer networks possessing dynamic covalent crosslinks constitute a class of materials with unique capabilities including the capacity for adapting to an externally applied stimulus. These covalent adaptable networks (CANs) represent a paradigm in polymer network fabrication aimed at the rational design of structural materials possessing dynamic characteristics for specialty applications and functions. Here, we explore several distinct approaches to CANs based on photochemically triggered responses. First, those in which the reversible bond formation, based on addition-fragmentation, occurs only during exposure to light will be discussed, enabling polymer network relaxation, photoinduced actuation and shape memory effects, and stress relaxation. Using liquid crystalline elastomer networks of this type, we will demonstrate the solution to fitting a square peg into a round hole, reversibly. Secondly, using thiol-thioester exchange chemistry, we will discuss the formation of a material that is capable of undergoing a bistable transition from a viscoelastic solid to a viscoelastic fluid, induced by light. Using this approach, we demonstrate recyclability, healing, and enhanced toughness of materials based on these types of networks. Ultimately, the potential for CANs-based materials to impact numerous materials applications will be presented in light of their distinctive array of material properties.

Bio: Professor Christopher N. Bowman received his B.S. and Ph.D. in Chemical Engineering from Purdue University in 1988 and 1991, respectively. After receiving his Ph.D., he began his academic career at the University of Colorado in January of 1992 as an Assistant Professor. Since that time Professor Bowman has built a program focused on the fundamentals and applications of crosslinked polymers formed via photopolymerization reactions. He works in the broad areas of the fundamentals of polymerization reaction engineering, polymer chemistry, crosslinked polymers, photopolymerizations and biomaterials. Professor Bowman has remained at Colorado throughout his academic career and is currently the Patten Endowed Chair of the Department of Chemical and Biological Engineering as well as a Clinical Professor of Restorative Dentistry at the University of Colorado at Denver.

On the (Virtual) Road

Kathryn A. Perrine
Kathryn A. Perrine

Kathryn Perrine (Chem) presented an invited talk on electrochemical surface corrosion, “Surface Chemistry and Catalysis at Complex Interfaces using PM-IRRAS,” at the #ChemistsLive, an American Chemical Society Cross-Division Virtual Live event Friday (Sept. 25) in the Ambient Pressure Spectroscopy in Complex Chemical Environments session (Catalysis Division).

This event followed the ACS Fall 2020 virtual National Meeting where graduate students of the Perrine group, Mikhail Trought and Chathura de Alwis, also presented their research on surface oxidation.

Seminar

Steven M. Firestine

Our Fall Seminar Series starts today! We welcome Dr. Steven Firestine from Wayne State University. The virtual seminar will begin at 3 p.m. today (Sept. 18) via Zoom.

Adventures in Antimicrobial Drug Discovery: Purine Biosynthesis and Spore Germination

Abstract: Antibiotics are arguably one of the greatest achievements in medical science, yet their utility is slowly being eroded by the rise of antibiotic-resistant bacteria. To combat this problem, new antibiotics focused on novel targets are desperately needed. Unfortunately, the pharmaceutical industry has divested from antimicrobial drug discovery leaving only small biotechnology companies and academia to find the next generation of antibiotics. One approach is to focus on underexplored pathways that are different between microbes and humans. Previous research has shown that the de novo purine biosynthetic pathway is different in bacteria, yeast and fungi than it is in humans. The difference is centered on the synthesis of the intermediate carboxyaminoimidazole ribonucleotide (CAIR). CAIR is synthesized from aminoimidazole ribonucleotide (AIR) and in microbes, two enzymes are required. In contrast, humans need only one enzyme. Genetic studies have shown that deleting the genes necessary for CAIR synthesis in microbes renders them avirulent. The Firestine laboratory has been focused on the interesting biochemical differences in the enzymes responsible for CAIR synthesis as well as exploiting this dissimilarity in drug discovery. The laboratory has also been exploring agents to prevent the germination of C. difficile spores. C. difficile is a challenging infection that is commonly found in hospitals and nursing homes. Spore germination is regulated by bile salts and we have discovered potent bile salt analogs which prevent germination in the nanomolar range even while in the presence of millimolar concentrations of the germinate. This seminar will outline our research on these projects.

Bio: Steve was born in Kalamazoo, MI, and attended the University of Michigan where he majored in chemistry.  While at UM, Steve conducted undergraduate research in the laboratory of Dr. James Coward working on the synthesis of fluorinated leucovorin. Steve graduated UM with high honors in chemistry and joined the Department of Medicinal Chemistry and Pharmacognosy at Purdue University where he studied medicinal chemistry and biochemistry under the direction of Dr. V. Jo Davisson. His doctoral studies focused on the study of AIR carboxylase and his research showed that this enzyme was different in microbes versus humans. Steve synthesized numerous nucleoside and nucleotide analogs including NAIR, which is the most potent inhibitor of AIR carboxylase known to date. Steve graduate in 1996 and conducted a Damon Runyon Walter Winchell Postdoctoral Fellowship in the laboratory of Dr. Stephen J. Benkovic at the Pennsylvania State University.  Steve conduct research into protein engineering and the generation of artificial transcriptional switches.  In 2000, Steve began his independent academic career as an assistant professor of medicinal chemistry at Duquesne University in Pittsburgh, PA.  There, his research focused on DNA bending agents as a mechanism to control gene expression. In 2005, Steve moved to Wayne State University and he was promoted to full professor in 2016. Since his arrival at WSU, Steve has been continuously funded by the National Institutes of Health where his research has focused on antimicrobial drug discovery.     

In Print

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.

Fellows

Dr. Rudy Luck

Professor Rudy Luck has been selected as a 2020 VIPEr (Virtual Inorganic Pedagogical Electronic Resource) Fellow.

The VIPEr Fellows are made up of 20 inorganic chemistry faculty from across the United States. This project is part of a 5-year grant from the National Science Foundation’s Improving Undergraduate STEM Education (IUSE) program. Its purpose is to develop, test, and refine a flexible, foundation-level inorganic chemistry course.

Visit https://www.ionicviper.org/ to learn more.

Congratulations Dr. Luck!

In Print

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.