NEWS OF THE WEEK SCIENCE
trans
ENZYME ACTIVITY: A MOVING EXPERIENCE Residue motions are found to be related to catalytic mechanism
T
HE RAPID MOTIONS OF AN
enzyme's amino acid residues when it's in its catalytic transition state have been captured for the first time. Assistant professor of biochemistry Dorothée Kern of Brandeis University and coworkers used nuclear magnetic resonance to detect backbone motion in cyclophilin A and found movement in one residue to be strongly correlated with the catalytic mechanism [Science, 295, 1520(2002)}. Researchers have previously studied static pictures (such as crystal structures) and motions of enzymes, but only in enzyme resting states, not during catalysis, Kern notes. "Because the transition state exists only fleetingly, enzyme dynamics during transition-state formation and decay have never been directly detected during an enzyme-catalyzed reaction in solution," explains Joseph J. Falke, professor of chemistry and biochemistry at the University of Colorado, in a Science commentary Kern and coworkers have now used N M R relaxation methods to look for motions in 160 amide nitrogens of the enzyme cyclophilin A during catalysis. They detected backbone movements in 10. In nine, these motions turned out to be associated primarily with substrate binding and unbinding. But rate analysis showed that movements of one residue, arginine-55, correlated strongly with catalysis. This makes sense, since arginine-55's side chain was already known to hydrogen-bond to the substrate and to play a key catalytic role. The study analyzed backbone HTTP://PUBS.ACS.ORG/CEN
movements but not side-chain motions, which can also be directly involved in catalysis. But Kern and coworkers are currently extending the technique to side chains. Protein motions have been a missing link in rational drug design, so pharmaceutical companies may be interested in the technique. As Kern explains, rational drug design has mainly been done by rigid-body docking, "but in the past 10 years, it's been shown that this usually doesn't work because you have to take in-
MERGER
MOTION PICTURE Motion of cyclophilin A's arginine55 residue (black) correlates strongly with catalytic action: the cis-trans conversion of the enzyme's substrate (light and dark green). Other numbered residues (red) are among nine whose motions are associated with substrate binding and unbinding. to account the mobility of your protein and drug. This is the kind of problem we are trying to attack in the long term with our experiments—to really go beyond static pictures and explore the protein as a dynamic object."— STU B0RMAN
PRELUDE
Mitsui, Sumitomo Ready Polyolefins Venture
M
itsui Chemicals and Sumitomo Chemical are set to combine their polyolefins businesses on April 1, before the full landmark merger between the two firms is completed. Separately, Mitsui says it will refurbish its Japanese polypropylene plants. Sumitomo Mitsui Polyolefin Co. will be headquartered in Tokyo, in the building Sumitomo Chemical currently occupies. The companies are proceeding with the merger following its approval by Japan's Fair Trade
Commission in December. In their fiscal year, which ended March 31, 2001, the companies' combined polyolefins operations recorded sales of about $1.65 billion. The final merger—on track to be completed in 2004—will create one of the world's largest chemical companies, with annual sales of some $20 billion. In advance of the polyolefins venture, Mitsui is revamping its polypropylene business. In late 2002, it will complete, at the cost of $90 million, a 300,000-metric-ton-per-year polypropylene plant near Osaka. Before then, Mitsui will shut down two smaller plants in Japan. On April 1, Mitsui will also dissolve and absorb its fully owned polypropylene subsidiary, Grand Polymer. Including long-term purchase agreements from other companies, Mitsui's annual polypropylene capacity is currently 703,000 metric tons. Mitsui's polypropylene decisions were made without formally consulting Sumitomo, the Sumitomo spokesman says. He adds that those actions could be reviewed after the April 1 merger.-JEAN-FRANÇOIS TREMBLAY
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FEBRUARY
25, 2002
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