Research by Associate Professor of Chemistry Mark Levandoski and recent biological chemistry graduates may hold the key—a molecular “key” to a larger protein “lock” leading to even greater discoveries behind cellular “doors.”
The Journal of Neuroscience, a major journal in the field, recently published a paper about the protein key research by Levandoski and graduates Seungmae Seo ’08, Jonathan Henry ’07, Amanda Lewis ’08, and Nan Wang ’09, all of whom are currently in doctoral programs. The paper, titled “The Positive Allosteric Modulator Morantel Binds at Non-canonical Subunit Interfaces of Neuronal Nicotinic Acetylcholine Receptors,” explains the protein research covering nearly four years of student-faculty collaboration.
“My students and I study the family of proteins in the nervous system that respond to nicotine. These proteins act as molecular portals—opening, closing, and reacting to ‘keys’ as a means of communication between cells,” Levandoski says. “For example, the proteins respond to acetylcholine, the compound that nerve cells use to communicate, and to nicotine, a molecule produced by tobacco plants that just happens to open the molecule’s ‘lock.’”
Levandoski continues, “We have demonstrated that there is a new lock located on the protein that, to our knowledge, no one has discovered, and that the lock is located in a different place and works in a different way. If, for example, nicotine works by tripping springs and pins in the lock, then our model compound known as morantel punches through on a new electronic keypad.”
By demonstrating evidence of a new key to unlock the protein’s binding sites, Levandoski and his student collaborators may well have contributed to a “new place to look to design drugs that block the effects of nicotine.
“One aspect of drug design is a process of making small changes to the key. If we are right, this result could offer new strategies for those in pharmaceutical settings to treat problems such as nicotine addiction.,” he says.
The National Institutes of Health and Research Corp. supported the protein research at Grinnell, which continues this summer as a Mentored Advanced Project (MAP) by biological chemistry majors Matt Doers ’10, Emily Jobe ’10, and Steve Sando ’11.
Levandoski is at work on a grant proposal to support the continued exploration. “We are launching into new questions to gather further evidence about how the binding sites communicate and work more effectively together than alone,” Levandoski says, moving from the “lock and key” analogy to one of clockworks with intricate, interconnected parts.