IN THIS ISSUE .
July 21, 2010
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It may look like a gyrating, Skittle-eating cloud, but it actually represents the active site of sulfite oxidase, an enzyme essential for normal neurological development in children. Look deep inside the channel opening to see a ball-and-stick model of a complex containing the element molybdenum (light blue ball) that helps pass an oxygen atom (red ball at far end of channel) to trigger a catalytic reaction. The channel itself is lined with a chloride ion (green) and water molecules (red). Knowing more about the enzyme's active site will help scientists better understand sulfite oxidase deficiency, a fatal neurological disease. Courtesy of bioinorganic chemist John H. Enemark at the University of Arizona.
While the healing process repairs injured tissues, it can go too far. Fibroblast cells normally aid healing, but too much of their activity can cause scarring. A team led by Lester Lau, a cell biologist at the University of Illinois at Chicago, discovered that a protein called CCN1 helps prevent fibroblasts from causing excessive scar tissue. They pinpointed the mechanisms underlying CCN1's effects on fibroblasts and showed that applying CCN1 at the site of a skin wound limits scar tissue formation. Because the wound healing process has many similarities across cells, organs and species, the results may shed light on how tissue repair occurs throughout the human body.
LEOPARD syndrome is a rare genetic disease that causes unsafe super-thick heart muscle in addition to facial, skin and sensory abnormalities. To better understand the disease, Ihor Lemischka, a stem cell biologist at Mount Sinai Medical Center, developed a new model using skin cells from people with LEOPARD syndrome. He and his team reprogrammed these cells into induced pluripotent stem (iPS) cells, which then became heart muscle cells showing telltale signs of the disease. Because the cells contain the exact genetic profile of individuals' diseased cells, this method could help scientists determine the cellular paths that lead to disease and help identify drug targets for the disorder.
Carbohydrates called glycans dot the surface of every cell in our bodies, and they play an important role in development. Now chemical biologist Carolyn Bertozzi and her team at the University of California, Berkeley, have created a tool for imaging the carbs' activity during the earliest stages of embryo development in zebrafish, a model organism. The scientists used a two-step method to label and simultaneously track two classes of glycans as they rapidly moved along the groove of dividing cells. In the future, scientists could use the technique to track other molecules and gain insights into key developmental events.
A chemical group called trifluoromethyl dramatically influences the properties of drugs and other important compounds, and pharmaceutical manufacturers often affix this group to certain drugs so they remain active longer. Despite its importance, scientists have struggled to figure out how to attach the chemical group in a convenient manner. A group led by MIT chemist Stephen Buchwald has found a way. With the right catalyst (a molecule that hastens the reaction), the scientists developed a process for adding the trifluoromethyl group that may ultimately help to streamline and lower the cost of drug synthesis and discovery.