Major ‘glue grant’ uncovers the power of enzymes.
Enzymes operate with seemingly superhuman powers—speeding up chemical reactions within cells in ways that still baffle scientists. What’s more, researchers have discovered thousands of previously unknown enzymes in recent years, but the function of at least half of them is not yet known. With this need in mind, efforts to discover enzyme functions have received a major boost with a $33.9 million, multi-institutional grant led by the University of Illinois.
“Enzymes are nature’s catalysts,” says John Gerlt, the LAS biochemist and enzymologist leading the effort. “The body needs them to generate energy, to grow, to synthesize new materials. For our muscles to move, it takes enzyme reactions. But it also means the reactions are happening very fast.”
Gerlt is the world’s authority on the enolase superfamily of enzymes and has been studying them for more than 20 years—well before anyone even knew they were part of a superfamily.
“My particular fascination with enzymes is that they can increase the rates of chemical reactions by a factor of 1015 compared to reactions in the absence of the enzyme,” Gerlt continues. “What is it about the three-dimensional structure of an enzyme that allows this very large enhancement to occur? How do they do that?”
Gerlt is actively looking for answers as the principal investigator of the prestigious “glue grant” funded by the National Institutes of Health. It is called a glue grant because it brings together nine institutions, with the University of Illinois acting as the lead.
The grant will be shared among the institutions over five years and will target five different enzyme superfamilies, including Gerlt’s specialty, the enolase superfamily. The program, formally known as the Enzyme Function Initiative, expands on an effort led by Gerlt since 2004. It also includes two other LAS researchers—John Cronan in microbiology and Jonathan Sweedler in chemistry.
In addition to discovering the unknown functions of various enzymes, Gerlt says there is a biological element to the program, as researchers also uncover the structures of these enzymes.
“We also want to understand how changes in the amino acid sequences of enzymes can change their function,” he adds.
If scientists can learn how nature generated new enzyme reactions by changing the amino acid sequence, they may be able to glean the secrets needed to bioengineer new enzymes. The result might be new catalysts that make it possible to create new drugs to combat long-standing ailments.
“If you want to understand how nature did it, you need to know the functions of the proteins,” Gerlt says. “That’s the missing information.”