ORGN 660 |
| The isoprenoid biosynthetic pathway produces over 30,000 naturally occurring molecules that perform a variety of essential functions in cells, including electron transport, stabilization of membrane structures, and signal transduction. Chain elongation, cyclopropanation, and branching are the three building reactions used to assemble the carbon skeletons of isoprenoid molecules from simpler substrates. The genes for farnesyl diphosphate (FPP) synthase, which catalyzes chain elongation, and chrysanthemyl diphosphate (CPP) synthase, which catalyzes cyclopropanation, from the sage brush Artemisia tridentata ssp speciformis were engineered to permit the construction of chimeric proteins by replacing regions of one protein with the corresponding regions from the other. All of the chimeric proteins fold to give active enzymes. Analysis of the reactions catalyzed by the wt and chimeric enzymes indicates that progressive substitution of regions in FPP synthase by those from CPP synthase shows a progression from chain elongation, to branching, to cyclopropanation. The evolving activities of the enzymes in the series can be explained by structural changes in the active site that alter substrate binding while maintaining a common chemical mechanism for the three reactions. |
|
Nakanishi Prize
1:00 PM-5:00 PM, Wednesday, 16 March 2005 Convention Center -- Ballroom 20A-B, Oral
Division of Organic Chemistry |