To Squelch Errant Enzymes Scientists at Johns Hopkins, New York University and Mount Sinai School of Medicine in New York have found a way to block the action of specific enzymes with a pivotal role in triggering cancers, hardening of the arteries and certain autoimmune diseases. Their research, described in this month's Nature Structural Biology, explains how a blockading molecule, called a bisubstrate analog, effectively prevents protein kinase enzymes from docking with other molecules in the body in short, from working. The researchers designed the bisubstrate analog using an improved understanding of how protein kinases normally work at the molecular level. They liken their work to the science that produced the protease inhibiting drugs that tipped the disease scales from fatal to chronic for many AIDS sufferers.
Protein kinases are widespread in the body.
The enzymes help ferry a small, reactive cluster of atoms containing phosphorus called a phosphoryl group to cell proteins. Once thought to be a mere housekeeping procedure, this transfer, researchers now know, is crucial to cells. Once a protein gains a phosphoryl group, Cole says, the protein changes, becoming a key player in cell reactions that prompt growth and reproduction. Experiments show that too much of a particular kinase can lead to tumors, and that autoimmune diseases such as arthritis and other inflammatory conditions probably involve kinases that are too efficient or overactive. Unlike other approaches to block protein kinases, the researchers say, the new technique works both on the molecules that donate the phosphoryl groups and on the protein molecules that accept them.