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MOONLIGHTING
One enzyme, one physiological role. That's how most scientists have traditionally looked at it. But there's a growing appreciation that some enzymes "moonlight"--that is, in addition to their "primary" catalytic function, they hold down one or more other important nonenzymatic jobs. Some of the most well-known moonlighting proteins--a term coined by Gregory A. Petsko, professor of biochemistry and chemistry at Brandeis University--are found in the lens of the eye. There you'll find a variety of enzymes that have abandoned their catalytic functions to play a structural role in the lens. These so-called crystallins in the lens include those known elsewhere in the body as lactate dehydrogenase and glutathione S-transferase. The enzyme gephyrin also moonlights. Gephyrin helps assemble a common molybdenum-containing enzyme cofactor. But it also plays an entirely unrelated structural role, anchoring proteins important to neurotransmission at the correct place in the brain. Then there's cytochrome c. This heme protein, found in the membranes of mitochondria, plays a crucial role in the electron-transport chain that cells use to produce energy. But cytochrome c also moonlights as a signal for apoptosis, the process by which cells commit suicide. In response to cell damage or other signals, cells release cytochrome c into the intermembrane space, where it stimulates apoptosis by forming a protein complex that signals apoptosis. Scientists are just beginning to understand how these and other moonlighting proteins manage to exert their dual functions. Whether an enzyme does its enzymatic or its moonlighting job may be determined by its physiologic location. Or an enzyme's moonlighting function may be controlled by the kind of protein complex it's in or the structural conformation it takes on. Other moonlighters, like cytochrome c, may simply use different binding sites on the same protein to do two different jobs. "Moonlighting is one way of getting more out of a limited protein repertoire," notes Shelley D. Copley, an associate professor of molecular, cellular, and developmental biology at the University of Colorado. And although moonlighting may well be widespread among proteins, predicting which proteins lead double lives remains challenging, she suggests. More practically, moonlighting may explain some of the side effects of drugs targeted at specific proteins. It may also hint at why some therapies that attempt to compensate for the loss of a protein could fail to make up for both that protein's normal and moonlighting roles.
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