However, the structural details of soluble guanylyl cyclase have remained elusive, Murad and Raman said. The protein is difficult to crystallize for structural analysis.
During a series of experiments that tracked the evolutionary development of the sensor protein identified in C. botulinum, dubbed SONO for "sensor of NO," the scientists were able to determine the three-dimensional structure of a related nitric oxide sensor in a different bacterium.
That structure will provide a key to unlock answers to some questions regarding the human NO receptor, soluble guanylyl cyclase (sGC), Raman said. "Having these structures now will help us attack that problem, because we know that this bacterial version of SONO is very similar to soluble guanylyl cyclase.
"If you know the structure of a protein, then you can develop therapeutics targeted to detect specific binding pockets on the molecule," Raman said. "That may allow us to control sGC activity in the absence of nitric oxide in such a way that we can combat cardiovascular and cerebrovascular disease."
And don't forget meat protection. The research team showed that C. botulinum uses SONO to detect nitric oxide, and then to flee its presence. "It's a strange topic for a strict vegetarian who has never touched meat in his life," Raman said.
Co-authors of the paper are: First author Pierre Nioche, Ph.D., research fellow in the Structural Biology Research Center; Vladimir Berka, Ph.D., senior research associate and Ah-Lim Tsai, Ph.D., professor, both of the Medical School Division of Hematology; and from the United Kingdom, Julia Vipond of the Health Protection Agency, Porton Down, Salisbury; and Nigel Minton of the Center of Biomolecular Sciences and Institute of Infection, Immunity and Inflammation, University of Nottingham.
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Contact: Scott Merville
scott.merville@uth.tmc.edu
713-500-3042
University of Texas Health Science Center at Houston
7-Oct-2004