UAB researchers draft 3-D protein map to aid stroke, cancer research

BIRMINGHAM, Ala. -- A new three-dimensional computer protein map is helping researchers at the University of Alabama at Birmingham (UAB) unravel the biological pathways that control brain-cell death after a stroke.

The new map will help identify new drug targets and test compounds to slow brain-cell death, halt brain cancer and improve pain control, the study authors said. The findings are published online in the Journal of Biological Chemistry.

Starting with known cell coordinates, biological structures and other data, UAB researchers focused on a protein called acid-sensing ion channel-1, or ASIC-1. This protein acts as a gateway on the surface of brain cells called neurons. The researchers generated a 3-D computer map of ASIC-1, which greatly simplifies the testing of any drug or compound designed to protect neurons, regulate their molecular interactions or isolate brain tumors.

"This protein ASIC-1 has a lot of little nooks and crevices where other molecules can sit and interact with the channel," said Yawar Qadri, a graduate student in the UAB Department of Physiology and Biophysics and the study's lead author. "With the map we've generated and the area we've described, researchers can fine-tune their ideas and tailor experimental compounds."

Dale Benos, Ph.D., chair of the Department of Physiology and Biophysics and a co-author on the study, said the ASIC-1 map is an invaluable tool in the ongoing search for new drugs that will specifically act on this biological pathway.

"The hope is that when a person has a stroke or they get diagnosed with a brain tumor, the patient can be given a drug that will keep his or her neurons alive and functioning longer, or we can keep cancer from migrating further," Benos said.

The study began with a toxin found only in the venom of the Trinidad chevron tarantula. In earlier laboratory research, this venom toxin proved capable of slowing neuronal death, inhibiting cancer growth and improving other biological disorders. UAB researchers wanted to simplify the search for non-venom agents that interact with ASIC-1 for positive results.

Qadri and his UAB colleagues generated the map of ASIC-1 with a software program called Modeller, developed by engineers at the University of California, San Francisco. The UAB ASIC-l map study includes validation work confirming its accuracy.

June 25, 2009