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Fall 2012

The Future of Light

by John Davis

Anatomy of a Mutation

‘Viral’ class seeks to create every possible single-point mutation on a protein.

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Meet the Researchers

Bryan Sutton

Bryan Sutton is an associate professor of cell physiology in the Department of Cell Physiology at TTUHSC.

 

 

David Knaff

David Knaff is director of the Center for Biotechnology and Genomics and a Horn professor in the Department of Chemistry and Biochemistry in the College of Arts & Sciences.

Rohan Nandkumar prepares his sample for crystallization.

Earlier this year in a class of about eight graduate students, the biotechnology master’s student from India literally pulled a mutation out of a hat. His task: to change one amino acid to another on a simple protein found in cyanobacteria.

It’s part of an experimental new “viral” class designed by two chemists at Texas Tech University and Texas Tech University Health Sciences Center (TTUHSC). The idea is to get many involved in the massive undertaking in order to discover how mutating each amino acid on the one protein alters the shape and function.

By doing so, the work of many may help researchers infer how mutations affect other proteins and cause some diseases, said Bryan Sutton, X-ray crystallographer and associate professor at TTUHSC.

“We want to examine what happens to a protein when you mutate every amino acid in a protein to every other possible amino acid,” Sutton said. “This has never been done. It’s been done to more or less of an extent on some other proteins. But it’s never been done completely on one protein. So we want to investigate the effects of mutation on one protein on the structure and enzymatic activity of that one protein to see what it would do.”

Proteins are large molecules that do most of the work in cells. They can serve as antibodies, enzymes, send messages, provide structural support, or transport or store other molecules.

The protein Sutton’s class is working with is called glutaredoxin and occurs in a cyanobacteria currently being studied by David Knaff, Horn professor of chemistry in the Department of Chemistry and Biochemistry.

Knaff said the microorganism, called Synechosystis sp., has adapted to live in water containing arsenic. The protein he and Sutton’s students are studying is responsible for changing arsenic to a less toxic form before being shuttled out of the bacterium’s body. This protein is fairly close to the human version of the glutaredoxin, which may play an antioxidant role against artherosclerosis in coronary arteries.

Knaff said he and Sutton came up with the class after collaborating on solving the first protein structure at Texas Tech.

“This is an example of the growing importance of collaborative research projects between the general academic campus and TTUHSC,” Knaff said. “Bryan has come up with a very imaginative idea for using this protein as the basis for a highly innovative teaching.”

Solving three-dimensional structures of proteins is something all top-tier research universities are doing, Knaff said, and Texas Tech University recently acquired the equipment to begin the process here. The detailed three-dimensional shape of a protein explains its special characteristics, such as its catalytic ability, its ability to recognize and bind substrates with high specificity and selectivity.

Glutaredoxin has 88 amino acids

Glutaredoxin has 88 amino acids. By the end of the experiment, students will have created about 1672 point mutations.

“In situations like sickle cell anemia, there’s a single mutation which causes hemoglobin in red blood cells to sickle,” Sutton said. “So, that’s a good example of one point mutation causing tremendous cellular changes and having tremendous implications in the way a particular human might live. That’s just one mutation. Hopefully, once we understand what all mutations do to this one protein, we can make similar inferences to provide cures or information to help treat sickle cell anemia or other diseases that are caused by point mutation.”

Sutton said The CH Foundation provided $75,000 to develop a course at Texas Tech and help to disseminate the class to Eastern New Mexico University, Midland Baptist University, Lubbock Christian University and others, such as the University of Illinois. Southern Illinois University at Edwardsville and Sam Houston State University also have expressed interest in contributing to the course.

“I hope by the time I retire, we’ll finish,” he said.

Students will use an X-ray crystallography machine especially designed for the class by Rigaku in Houston. Sutton said the screen machine is safe and simple to use, but provides a high-quality X-ray, so close up, it reveals the atoms in the protein.

“We have the first version of that machine here now, and it’s working and produced protein structures of glutaredoxin here a few months ago,” he said. “It’s quite impressive. Once we have all mutations together, we can see what the consequences are for the molecules that will actually crystallize. We’ve already seen some fairly dramatic changes that occur on this molecule with the 10 mutations we’ve done.”

About the Texas Tech University Health Sciences Center

Texas Tech University Health Sciences Center (TTUHSC)

Beginning in 1969 as Texas Tech University School of Medicine, today the Texas Tech University Health Sciences Center (TTUHSC) is a seven-school university located in Abilene, Amarillo, Dallas/Fort Worth, El Paso, Lubbock, Midland and Odessa.

The goal of the TTUHSC is to become known as an institution that advances knowledge for students and practicing health care professionals through educational opportunities and research while providing quality patient care and service.

Connect with TTUHSC on Facebook, Twitter, YouTube, Foursquare and Flickr.

 

John Davis is a Senior Writer in the Office of Communications & Marketing at Texas Tech University. Video produced by Scott Irlbeck, Senior Editor of Research & Academic Communications for the Office of the Vice President for Research at Texas Tech University.

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