Walker Wins Top Chemistry Award for Research

March 27, 2000

Contact: F. Ann Walker, 520-621-8645, awalker@u.arizona.edu
She will be staying at the Argent Hotel during the conference,
Tel: 415-974-6400, Fax: 415- 543-8268.

SAN FRANCISCO - Novel proteins from blood-sucking insects and biological molecules called cytochromes that play a basic role in cellular energy transport are at the heart of University of Arizona Professor F. Ann Walker's research.

The American Chemical Society (ACS) is awarding Walker its highest prize given specifically to a woman for outstanding service to chemistry. The Francis P. Garvan - John M. Olin Medal is being awarded to Walker for her service to the profession of chemistry, her outstanding success in research, and her commitment to training students in research - particularly undergraduate students.

The award consists of a gold medal and bronze replica, a certificate, up to $1,000 toward travel expenses, and $5,000 in cash. The ACS will present the award at its annual meeting March 26 - 30 in San Francisco. Walker's prize lecture on Monday, March 27, is "Understanding Low-Spin Ferriheme Centers of the Cytochromes: the Importance of Pulsed EPR Spectroscopy".

Walker will also talk on her work at the Women's Chemistry Luncheon on Tuesday, March 28. Her noon lecture is titled, "Nitric Oxide and Blood-Sucking Insects: The Intersection of Entomology, Inorganic Biochemistry, Medicine and Anthropology."

Walker began her work with cytochromes long before joining the UA in 1990 as a professor of chemistry and biochemistry. Cytochromes play essential roles in many aspects of biology. They play a fundamental role in energy transport between cells.

A cytochrome molecule consists of a protein chain and a non-protein, iron-containing porphyrin core. Envision a doughnut: If the organic part, or porphyrin ring, is the doughnut, the iron atom is nestled in the hole and the protein is attached to part of the outer edge of the doughnut.

Also attached to the outer edge of the doughnut, and above and below the iron atom, are organic subunits called ligands. One of Walker's goals is finding out exactly how these ligands are oriented and how they help determine the specific properties of the individual cytochromes.

Despite their importance in biological systems, many of the cytochromes have not been structurally well-characterized. One problem is the protein. Current methods of analysis do not give detailed information about such a large molecule.

However, Walker has found an approach to indirectly gain structural information. Her group uses model porphyrin rings - without an attached protein - on which a variety of ligands can be easily substituted. Systematically changing a ligand changes the properties of the porphyrin ring and of the other ligand attached to the iron.

They then analyze these model compounds using various spectroscopic techniques that give complementary pieces of information about their structure. They combine electron paramagnetic resonance (EPR), Mossbauer spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. They also use the same techniques to analyze cytochromes isolated from biological samples. Comparing the results tells about cytrochrome structure in greater detail.

"We are doing very fundamental research," Walker explains. "I'm really interested in why the various energy levels of the electrons cause these molecules to behave the way they do."

Since it isn't possible to do all of the various types of spectroscopy at the University of Arizona, Walker collaborates with colleagues in the United States and in Europe. Alfred Trautwein's lab in Lubeck, Germany, for example, performs the Mossbauer spectroscopy. Andrew Thompson's group in England is responsible for magnetic circular dichroism (MCD) analysis.

Walker's work in characterizing cytochromes also led to her work with heme proteins from blood-sucking insects. She began collaborating with Jesus Valenzuela, a former UA graduate student in biochemistry, and former UA entomologist Jose Ribiero, both now with the National Institutes of Health.

Ribiero noticed that the saliva of Rhodnius prolixus, or kissing bug, is red. He knew that "heme" (iron-containing pigment) was present. He asked Walker if she could further help unravel the structure of these proteins. They used Walker's spectroscopic approach, along with recombinant DNA technology, in identifying a new family of heme proteins that store and transport nitric oxide.

When the kissing bug bites its victim, it injects a small amount of the nitric oxide-laden heme protein. Among other things, this dilates the blood vessels, bringing more blood to the site of the bite, and temporarily neutralizes the victim's immune response. The insect then has plenty of time to get its meal before the person even realizes he or she has been bitten.

Kissing bugs are responsible for transmission of Chagas' disease, a potentially fatal disease that affects from 16 million to 18 million Latin Americans alone. This new insight into the biochemistry of these insects helps Ribiero and Valenzuela further the understanding about how this disease is transmitted.

As for future achievements in her field, Walker says:

"I would like to see the ability to analyze protein structures with high enough resolution to tell me whether what I've been saying all this time is right or not. What really does create these spectroscopic signals we see? I would be willing to bet that these ligands are not oriented exactly as we think they are. We may never be able to completely model what's going on. It is nature that's in complete control."

Walker is known for outstanding teaching. She has supervised 23 master's and 7 doctoral students. Especially impressive, however, is that she has given more than 100 undergraduates the opportunity to learn first-hand about conducting scientific research.

A number of these undergraduates have gone on to their own distinguished careers in chemistry. They include UA graduates Richard Koerner (doctorate from University of California - Davis, postdoctoral researcher at MIT, assistant professor at Penn State), Joshua Wright (M.D. degree from Medical College of Wisconsin, Resident in Emergency Medicine, Detroit), and Kareem Chehade (doctoral candidate, University of Kentucky), and about two dozen others.

Walker says she hopes that by working in her lab, students will learn how to approach a problem, interpret the results of their experiments, and design the next round of experiments to answer the questions posed by their chosen research problem. Or, as she explains, "To enable them to go into the lab themselves someday and make their own discoveries, find their own cures, or do whatever it is they would like to do."