ARTICLE | Tools & Techniques

Weighing the evidence in GPCR case

November 13, 2000 8:00 AM UTC

Membrane proteins have proved very difficult to crystallize, with only a single example of a G protein-coupled receptor structure in the public domain. Indeed, getting crystals is the first and most difficult step on the road to obtaining a protein's structure. Thus, the belief that 3-Dimensional Pharmaceuticals Inc. had produced the crystals of a second GPCR promised significant improvement in the ability of companies to do structure-based drug design on a key family of proteins. But earlier this month DDDP announced that it did not have the crystals, after all.

GPCRs make up the largest family of validated drug targets - about 60 percent of approved drugs act at GPCRs. GPCRs are such prominent drug targets because they are responsible for most cellular signaling and they make up about 3 percent of the human genome, based on comparison with the worm genome. GPCRs are responsible for the ability to see and smell and are used by cells to detect extracellular stimuli such as calcium, hormones and neurotransmitters...