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Exploiting Protein Symmetry To Design Light-Controllable Enzyme Inhibitors

Reisinger, Bernd ; Kuzmanovic, Natascha ; Löffler, Patrick ; Merkl, Rainer ; König, Burkhard ; Sterner, Reinhard


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.

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