Exploiting Protein Symmetry To Design Light-Controllable Enzyme Inhibitors

Abstract

The activity of the metabolic branch-point enzyme
PriA from Mycobacterium tuberculosis (mtPriA) can be
controlled reversibly by light. Two-pronged inhibitors based
on the dithienylethene scaffold were designed utilizing
mtPriA�s natural rotational symmetry. Switching from the
flexible, ring-open to the rigid, ring-closed isomer reduces
inhibition activity by one order of magnitude.