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Atomic-resolution views suggest function of enzyme that regulates light-detecting signals in eye
Date:10/7/2008

An atomic-resolution view of an enzyme found only in the eye has given researchers at the University of Washington (UW) clues about how this enzyme, essential to vision, is activated. The enzyme, phosphodiesterase 6 (PDE6), is central to the way light entering the retina is converted into a cascade of signals to the brain.

This particular form of the enzyme comes from the cone photoreceptors of the retina and has not been well-researched, in contrast to its rod form. Rods are involved in night vision and motion sensation; the cones are responsible for color sensitivity, visual acuity, daylight vision, and adjustment to bright light.

The section of the enzyme molecule that most interests the researchers is the so-called GAF A domain. A small messenger molecule, cGMP, binds to the GAF A domain to regulate the enzyme.

"The domain binds to this small molecule with extremely high sensitivity," said UW biochemist Clemens Heikaus, who along with Sergio E. Martinez, now a research associate at Rutgers, carried out the study. "From our structure, we can infer why it prefers cGMP over other messenger molecules." He added that the domain is quick in recognizing and responding to the messenger molecule to create an instantaneous flow of information to the brain.

Using X-ray crystallography and nuclear magnetic resonance, the researchers discovered that the enzyme undergoes major structural changes upon binding of the cGMP molecule.

Before binding occurs, the GAF domain is like an outstretched palm with the fingers wiggling, Heikaus said. After the cGMP molecule binds, the GAF domain closes and becomes less dynamic. In this state it looks more like a closed fist.

Further analysis of the consequences of this conformational change may lead to a better understanding of how the photoreceptor PDE helps regulate the path of signals that enable us to see, as well as provide general information on proteins with GA
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Contact: Leila Gray
206-685-0381
University of Washington
Source:Eurekalert  

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