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

F domains.

"The addition of a simple, small molecule to the GAF domain affects the entire PDE enzyme," Heikaus said. Researchers think the binding to the domain may act as a switch that turns on the enzyme.

The research findings were published in the Sept. 19 Journal of Biological Chemistry. The article was selected as a Paper of the Week. The journal cover featured a striking image of the iris of Heikaus' eye, photographed by UW ophthalmology imaging supervisor Brad Clifton. Superimposed in the center of the pupil was a three-dimensional structure of the GAF domain.

In humans, GAF-containing proteins are rare. In plants and bacteria, GAF domains are widespread and are specialized for binding a variety of molecules. Some of these plant and bacteria GAF domains are important in detecting light, but they do so through a mechanism that is completely different from vision in vertebrate animals.

GAF domains emerged more than 3 billion years ago in early forms of life, and remained as animals and humans evolved, a phenomenon evolutionary biologists call conservation. Human GAF domains have similar protein folds, and a similar way of binding signal-triggering molecules inside a "pocket," as do GAF domains in more primitive creatures.

Humans have only a few kinds of GAF domains, all of which are in enzymes within the PDE family. They perform important functions not only in vision but also in hearts, lungs, and blood vessels. PDE5, an enzyme closely related to PDE6, is the therapeutic target for sildenafil, known by the trade name Viagra. In some men, this drug also inhibits PDE6 in the eyes, causing a temporary change in color vision.

More knowledge of the basic mechanisms of PDEs in vision may lead someday to better drug treatment for loss of eyesight from damaged retinas, such as occurs in night blindness and retinitis pigmentosa.


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Contact: Leila Gray
206-685-0381
University of Washington
Source:Eurekalert  

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