Interdisciplinary PhD in Structural and Computational Biology and Quantitative Biosciences

Crystallizing Science, One Protein at a Time

Crystal solved by crystallography in the Rayment LabIt’s square one. It’s step one. It puts the “basic” in basic science. How ever you describe it, understanding protein structure and function through what’s called X-ray crystallography is an important approach in many areas of biochemistry, including drug design. And it’s a technique many researchers in the Department of Biochemistry at the University of Wisconsin–Madison specialize in.

A computer repairperson can’t fix or improve a computer without knowing anything about the parts, and a scientist can’t work with a protein properly without knowledge of its basic structure first. If a mutation in a protein causes disease, knowing where the mutation is located — and its effects there — could help find a way to fight the disease. Oftentimes, structure holds the key.

The process required to determine, or “solve,” the structure of a protein through X-ray crystallography has changed rapidly, like many scientific techniques. It’s gone from long and complex to an approachable technique that is used by many researchers.

In crystallography, the protein of interest has to be purified and coaxed into crystallizing. Next the crystal is exposed to X-rays, which are scattered by the crystal, and data are collected on these scattered X-rays. Mathematical equations and computer programs take it from there, helping the researcher generate a three-dimensional image of the protein. This process once took decades. As science advanced it began to take five years, then one, and today, if all goes well, just a matter of weeks.

“Our main goal is to be able to see what a protein or other molecule looks like in three dimensions,” says Hazel Holden, a professor in the UW–Madison Department of Biochemistry. “In the case of enzymes, we want to understand how they catalyze their reactions, which can only be fully understood by a three-dimensional picture.”

To read the rest of this feature story, see the link below.

URL: https://biochem.wisc.edu/news/2017/news-biochemistry-crystallography-2017-09-14