Form and function in enzyme activity

April 6, 2012 By Angela Herring
Mary Jo Ondrechen and Penny Beuning recently received an NSF grant to study enzyme activity in the lab and computationally. Credit: Dominick Reuter

Many industrial chemistry applications, such as drug or biofuel synthesis, require large energy inputs and often produce toxic pollutants. But chemistry and chemical biology professor Mary Jo Ondrechen said enzymes — proteins that increase the rate of chemical reactions in the body — could be used to effectively replace standard industrial processes.

“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 , 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, it’s 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 enzyme’s 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 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.

Ondrechen’s team, using a method she developed 10 years ago, will be able to predict which remote amino acids will impact reactivity. Beuning’s 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 ’s composition and observe how it affects its function.

Beuning’s experimental data can be used to train the computational method to make even better predictions about which are important to catalysis.

“There is a nice synergy between our interests,” she said. “We can take the computational work from Ondrechen’s lab, add the experimental work to it and then take the experimental results and say, ‘Did it work? Are there subtleties that we’re missing?’”

By building a library of enzymes known to have remote amino-acid activity, the group can eventually begin to answer fundamental research questions in the quest to improve industrial enzymatic chemistry techniques.

Explore further: Research breakthrough for the protein factories of tomorrow

Related Stories

Research breakthrough for the protein factories of tomorrow

September 22, 2006

Using a kind of molecular ‘hip joint operation,’ researchers at Uppsala University have succeeded in replacing a natural amino acid in a protein with an artificial one. This step forward opens the possibility of creating ...

Copycat protein finds a perfect match

November 19, 2010

As proteins are synthesized during messenger RNA translation, fresh amino acids are delivered to the ribosome of the cell by nucleic acid molecules known as transfer RNAs (tRNAs). Each amino acid has a cognate tRNA, and the ...

Organic chemistry: Amino acids made easy

May 4, 2011

Amino acids are the building blocks of proteins. There are 22 different amino acids and they can combine in a myriad ways to form a vast array of proteins. All amino acids except glycine are chiral molecules, meaning they ...

Biologists uncover a novel cellular proofreading mechanism

November 11, 2011

(PhysOrg.com) -- To make proteins, cells assemble long chains of amino acids, based on genetic instructions from DNA. That construction takes place in a tiny cellular structure called a ribosome, to which amino acids are ...

Recommended for you

New chemistry makes strong bonds weak

July 28, 2015

Researchers at Princeton have developed a new chemical reaction that breaks the strongest bond in a molecule instead of the weakest, completely reversing the norm for reactions in which bonds are evenly split to form reactive ...

Making polymers from a greenhouse gas

July 28, 2015

A future where power plants feed their carbon dioxide directly into an adjacent production facility instead of spewing it up a chimney and into the atmosphere is definitely possible, because CO2 isn't just an undesirable ...

New material opens possibilities for super-long-acting pills

July 28, 2015

Medical devices designed to reside in the stomach have a variety of applications, including prolonged drug delivery, electronic monitoring, and weight-loss intervention. However, these devices, often created with nondegradable ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.