Chemical Science chooses Shafaat group’s model of CO2-converting enzyme, carbon monoxide dehydrogenase, as Pick of the Week

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Professor Hannah Shafaat group’s article “Electronic isomerism in heterometallic nickel–iron–sulfur cluster models substrate binding and cyanide inhibition of carbon monoxide dehydrogenase” is highlighted by the publisher Royal Society of Chemistry as ChemSci pick of the week. 

Carbon monoxide dehydrogenase (CODH) enzymes found within bacteria contain nickel-iron-sulfur clusters that efficiently catalyze the reversible conversion of carbon dioxide to carbon monoxide, yet the underlying mechanism is poorly understood. To elucidate the connection between the structure and properties of this enzyme, the Shafaat group has developed a protein-based model of CODH that has an analogous active-site cluster to probe electron movement through different stages of the reaction using numerous spectroscopic techniques. This mimic of CODH offers new insights into the mechanism, which will benefit the design of synthetic catalysts for more efficient carbon conversion.

“The native CODH enzyme has been particularly challenging to study because it contains numerous metal-containing cofactors, which complicates spectroscopy. It is also highly sensitive to oxygen and difficult to produce,” said Hannah Shafaat. “Our model reproduces key features of the enzyme and shows how electrons flow through the cluster to activate substrates at the unique nickel ion.” 

The research is published in Chemical Science, the Royal Society of Chemistry’s peer-reviewed flagship journal. The first author on the paper is Dr. Luke Lewis, former graduate student with Professor Shafaat at The Ohio State University (OSU), and co-authors include UCLA’s Dr. Yuri Lee and Jose Sanabria-Gracia and Dr. Adam Jenkins, both at OSU.   

The Shafaat group works on metalloenzymes to catalyze small-molecule activation reactions, with applications ranging from alternative energy storage to biosynthesis to the origins of life. Shafaat and her group moved to UCLA in 2023 from The Ohio State University. 

Professor Hannah Shafaat received her B.S. in Chemistry from the California Institute of Technology (Caltech) in 2006 and her Ph.D. from the University of California, San Diego (UCSD) in 2011. Shafaat began her independent research career at The Ohio State University in 2013 and joined the UCLA faculty as a Professor in 2023.

Article by Zhuoying Lin, UCLA Department of Chemistry & Biochemistry,