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.
Keywords:
biosynthesis; enzyme catalysis; enzyme inhibitors; molecular switches; photochromism.
Copyright © 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antitubercular Agents / chemical synthesis
-
Antitubercular Agents / chemistry*
-
Antitubercular Agents / pharmacology
-
Bacterial Proteins / antagonists & inhibitors
-
Bacterial Proteins / chemistry*
-
Drug Design*
-
Enzyme Inhibitors / chemical synthesis
-
Enzyme Inhibitors / chemistry*
-
Enzyme Inhibitors / pharmacology
-
Histidine / biosynthesis
-
Isomerism
-
Light*
-
Molecular Dynamics Simulation
-
Mycobacterium tuberculosis / enzymology*
-
Photochemistry
-
Protein Binding
-
Protein Structure, Secondary
-
Tryptophan / biosynthesis
Substances
-
Antitubercular Agents
-
Bacterial Proteins
-
Enzyme Inhibitors
-
Histidine
-
Tryptophan