Researchers Awarded $33.9 Million Grant to Study Enzyme Functions

The “glue grant” – so-called because it brings together multidisciplinary groups of investigators – was awarded to provide resources to tackle the “complex problems that are of central importance to biomedical science but are beyond the means of any one research group,” according to the NIGMS.

Gerlt’s team will develop a strategy for discovering the functions of unknown, or uncharacterized, enzymes discovered in genome-sequencing projects.

“Genome projects have taught us that many of nature’s enzymes have unknown functions that need to be discovered,” said Gerlt, an expert on the enolase superfamily of enzymes.

Enzymes are proteins that catalyze the chemical reactions required for life, and enable organisms to live in complex environments and adapt to a variety of conditions.

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

Gerlt and co-researcher Patricia Babbitt, of the University of California at San Francisco, have led the way in developing a novel method to determine an uncharacterized protein’s function. 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 the sequence data that have not yet been deciphered; it also could provide a way to learn more about metabolic pathways crucial to all organisms.

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

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

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

“This program gathers together an outstanding group of researchers who will use their expertise in enzymology, structural biology, computational modeling and bioinformatics to develop an approach to associate enzymatic functions with genes in thousands of organisms,” said Warren Jones, the chief of the biochemistry and biorelated chemistry branch in the division of pharmacology, physiology and biological chemistry at the NIGMS.