title: 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.
authors: Institut für Biophysik und physikalische Biochemie, Universität Regensburg, 93040 Regensburg (Germany).
authors: Bernd
authors: B
authors: Reisinger
authors: Natascha
authors: N
authors: Kuzmanovic
authors: Patrick
authors: P
authors: Löffler
authors: Rainer
authors: R
authors: Merkl
authors: Burkhard
authors: B
authors: König
authors: Reinhard
authors: R
authors: Sterner
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006639:Histidine / Q000096:biosynthesis; D007536:Isomerism; D008027:Light; D056004:Molecular Dynamics Simulation; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D010777:Photochemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D014364:Tryptophan / Q000096:biosynthesis
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D006639:Histidine; D014364:Tryptophan
keywords: biosynthesis; enzyme catalysis; enzyme inhibitors; molecular switches; photochromism