Simeth, Nadja A. and Kinateder, Thomas and Rajendran, Chitra and Nazet, Julian and Merkl, Rainer and Sterner, Reinhard and Koenig, Burkhard and Kneuttinger, Andrea C. (2021) Towards Photochromic Azobenzene-Based Inhibitors for Tryptophan Synthase. CHEMISTRY-A EUROPEAN JOURNAL, 27. pp. 2439-2451. ISSN 0947-6539, 1521-3765
Full text not available from this repository. (Request a copy)Abstract
Light regulation of drug molecules has gained growing interest in biochemical and pharmacological research in recent years. In addition, a serious need for novel molecular targets of antibiotics has emerged presently. Herein, the development of a photocontrollable, azobenzene-based antibiotic precursor towards tryptophan synthase (TS), an essential metabolic multienzyme complex in bacteria, is presented. The compound exhibited moderately strong inhibition of TS in its E configuration and five times lower inhibition strength in its Z configuration. A combination of biochemical, crystallographic, and computational analyses was used to characterize the inhibition mode of this compound. Remarkably, binding of the inhibitor to a hitherto-unconsidered cavity results in an unproductive conformation of TS leading to noncompetitive inhibition of tryptophan production. In conclusion, we created a promising lead compound for combatting bacterial diseases, which targets an essential metabolic enzyme, and whose inhibition strength can be controlled with light.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ALPHA(2)BETA(2) COMPLEX; 3-DIMENSIONAL STRUCTURE; ANTIBACTERIAL ACTIVITY; ALLOSTERIC REGULATION; CRYSTAL-STRUCTURES; ESCHERICHIA-COLI; OPTICAL CONTROL; ACTIVE-SITES; IN-VIVO; COMMUNICATION; antibiotics; azo compounds; enzymes; inhibitors; photopharmacology |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Reinhard Sterner Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Rainer Merkl Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Burkhard König |
| Depositing User: | Petra Gürster |
| Date Deposited: | 21 Apr 2021 14:31 |
| Last Modified: | 21 Apr 2021 14:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43106 |
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