Enzymatic reactions are cleaner, produce fewer byproducts and use less energy, she explained. But attempts to replicate natural enzymes for industrial applications are limited by our incomplete knowledge of these proteins.

Ondrechen and Penny J. Beuning, an assistant professor of chemistry and chemical biology, have received a three-year, $565,000 grant from the National Science Foundation to develop a better understanding of enzyme activity.

If you want to design proteins to catalyze a particular reaction, its good to understand how they work, said Ondrechen.

Enzymes, she explained, are made up of a string of amino acids coded by the gene sequence. Each amino acid has a different role in the protein: Some are structurally important while others are required for the enzymes catalytic properties.

There are cavities on the surface of a protein where a molecule can come in and sit down, Ondrechen said. The enzyme does a reaction on it and the product goes away.

The current body of research on enzyme activity mostly focuses on the amino acids in that cavity, which come into direct contact with the reactive molecule. But over the years, some research has suggested that amino acids far away from the active site also play a role in catalysis.

Ondrechens team, using a method she developed 10 years ago, will be able to predict which remote amino acids will impact reactivity. Beunings team will test these predictions experimentally.

My lab is really interested in specificity of enzymes, Beuning said. We look enzymes and figure out how they recognize their substrates.

To do this, her team takes a protein engineering approach in which they manipulate the enzymes composition and observe how it affects its function.

Beunings experimental data can be used to train the computational method to make even better predictions about which amino acids are important to catalysis.

Link:
Form and function in enzyme activity