UW facility helps scientists explore hidden life of molecules

Whether it’s the secrets of sweeteners or viruses, studying molecular structure is where the action is today in biochemistry.

Today, biochemists increasingly rely on nuclear magnetic resonance spectrometers to study the proteins that govern life. The machines can reveal how these molecules take form and if their three-dimensional shape changes as they carry out their functions.

The new biochemistry building includes a laboratory large enough for the department’s NMR facility to bring all its machines under one roof. There is room to spare for future NMR machines, which may stand more than 20 feet tall, hold hundreds of miles of superconducting wire and carry a price tag of $6 million or more.

“We’re a national facility here to serve the scientific community,” says John Markley, the UW–Madison Steenbock professor of molecular structure. Markley directs the NMR Facility at Madison with five machines and staff of 10. “We analyze samples from researchers and train people who come here to do experiments with the machines.”

The machines operate on the same principle as the Magnetic Resonance Imaging (MRI) machines used in hospitals to diagnose diseases without surgery. Today’s NMR machines get the detailed resolution they need to analyze molecular structure by using powerful magnetic fields on small samples of purified compounds.

With this technology, scientists can map the atoms in a molecule. NMR machines briefly create a strong magnetic field, to which some atomic nuclei respond by changing their alignment. Scientists can detect characteristic signals from this movement and use it to identify the atoms and their positions.

In June’s issue of Nature Structural Biology, for example, Markley and UW–Madison coworkers described the structure of brazzein, a compound 2,000 times sweeter than sugar. Brazzein, isolated from a West African fruit, is one of a handful of compounds known to taste sugary to humans and other primates.

Markley says knowing brazzein’s structure and how it binds to taste receptors will help scientists understand what gives the protein its flavor.

NMR methods also can be used to study fats and oils, which give many foods their distinctive flavor and texture. Food chemist Kerry Kaylegian, who works at the University’s Center for Dairy Research, has used NMR in combination with other modern technology to develop a prototype of butter that spreads right out of the refrigerator.

NMR machines have become larger over the years, which boosts both performance and cost, according to Markley. “Larger machines are useful because they make new types of experiments possible,” he says. Today’s largest machines are 750-megahertz to 800-megahertz class. Manufacturers are now developing 1000-megahertz models with even greater sensitivity.