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CHAMPAGNE, III. – A team of researchers led by University of Illinois biochemistry professor John A. Gerlt received a five-year, $ 33.9 million grant from the National Institutes of General Medical Sciences to study the functions unknown enzymes.

The “glue grant” – so called because it brings together multidisciplinary groups of researchers – was awarded to provide resources to tackle “complex problems which are of central importance to biomedical science but beyond the means of. ‘one research group in particular,’ according to NIGMS.

Gerlt’s team will develop a strategy to uncover the functions of unknown or uncharacterized enzymes discovered in genome sequencing projects.

“Genome projects have taught us that many enzymes in nature have unknown functions that must be discovered,” said Gerlt, an expert in the enolase enzyme superfamily.

Enzymes are proteins that catalyze the chemical reactions necessary for life and allow organisms to live in complex environments and adapt to various conditions.

“We have sequences for over 10 million proteins and we could know the specific functions of half of them,” said Gerlt. “But what does the other half do? If we knew their functions, imagine how we could use them to identify new drug targets or provide catalysts used in industry.”

Gerlt and her co-researcher Patricia Babbitt, of the University of California, San Francisco, paved the way for the development of a new method to determine the function of an uncharacterized protein. Their approach uses computational methods to narrow the range of possible substrates for the enzyme.

Gerlt says this project is a potentially powerful way to exploit sequence data that has yet to be deciphered; it could also provide a way to learn more about metabolic pathways crucial for all organisms.

For the glue grant, officially known as the Enzyme Function Initiative, Gerlt and Babbitt assembled a team of researchers from several disciplines to determine the structure of an unknown enzyme, then, by calculation, determine a “list of results ”of possible substrates, numbered in the tens rather than the thousands.

The research team includes scientists from Albert Einstein College of Medicine, Boston University, Texas A&M University, University of New Mexico, University of Utah, Vanderbilt University School of Medicine and University of Virginia.

The team also includes a microbiology group led by John Cronan, professor of microbiology at Illinois, and Jonathan Sweedler, professor of chemistry at Illinois.

“This program brings together an exceptional group of researchers who will use their expertise in enzymology, structural biology, computer modeling and bioinformatics to develop an approach for associating enzymatic functions with genes in thousands of organisms,” said Warren Jones, head of biochemistry. and the bioconnected chemistry branch of the pharmacology, physiology and biological chemistry division of NIGMS.


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