Ancient origins of allosteric activation in a Ser-Thr kinase

Abstract

Evolution of a kinase allosteric site Enzyme activity is often regulated by conformational changes coupled to binding of an effector at an allosteric site, a feature especially important for enzymes involved in signaling cascades. Hadzipasic et al. studied the origins of allosteric regulation of Aurora A, a kinase involved in progression of the eukaryotic cell cycle. Aurora A is allosterically regulated through the binding of an effector protein named TPX2, which also targets the kinase to spindle microtubules. By reconstructing ancestor kinase sequences, they found that TPX2 bound to an early Aurora A but had very weak activation that was gradually strengthened by evolution of an allosteric network within the kinase. An evolutionary advantage from localizing the active protein at the mitotic spindle may have driven the development of this regulatory mechanism. Science , this issue p. 912