Catalytic dry run

Enzymes are constantly rehearsing, say Elan Eisenmesser, Dorothee Kern (Brandeis University, Waltham, MA), and colleagues. They find that, even before a substrate appears on the scene, an enzyme flexes rapidly through its catalytic motions.

Kern has been looking at enzymes for many years, but in Eastern Europe her work was constrained. “We didn't have big enough NMR machines to look at the protein, so we were looking at the substrate during catalysis,” she says. But now money and NMR technologies have caught up with Kern's ambitions. With new NMR methods, different protein conformations can be quantitated, thus yielding the kinetics of protein motion.

The Brandeis group applied these methods to the prolyl cis-trans isomerase cyclophilin A (CypA). They first mapped movements during catalysis, and then found that very similar movements happened...