Kneuttinger, Andrea C. and Winter, Martin and Simeth, Nadja A. and Heyn, Kristina and Merkl, Rainer and Koenig, Burkhard and Sterner, Reinhard (2018) Artificial Light Regulation of an Allosteric Bienzyme Complex by a Photosensitive Ligand. CHEMBIOCHEM, 19 (16). pp. 1750-1757. ISSN 1439-4227, 1439-7633
Full text not available from this repository. (Request a copy)Abstract
The artificial regulation of proteins by light is an emerging subdiscipline of synthetic biology. Here, we used this concept to photocontrol both catalysis and allostery within the heterodimeric enzyme complex imidazole glycerol phosphate synthase (ImGP-S). ImGP-S consists of the cyclase subunit HisF and the glutaminase subunit HisH, which is allosterically stimulated by substrate binding to HisF. We show that a light-sensitive diarylethene (1,2-dithienylethene, DTE)-based competitive inhibitor in its ring-open state binds with low micromolar affinity to the cyclase subunit and displaces its substrate from the active site. As a consequence, catalysis by HisF and allosteric stimulation of HisH are impaired. Following UV-light irradiation, the DTE ligand adopts its ring-closed state and loses affinity for HisF, restoring activity and allostery. Our approach allows for the switching of ImGP-S activity and allostery during catalysis and appears to be generally applicable for the light regulation of other multienzyme complexes.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | STRUCTURAL EVIDENCE; OPTICAL CONTROL; ACTIVE-SITE; INHIBITORS; DESIGN; EVOLUTION; SWITCHES; BARREL; allosterism; enzyme catalysis; enzyme inhibitor; photoswitches; synthetic biology |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Reinhard Sterner |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Jan 2020 10:01 |
| Last Modified: | 10 Jan 2020 10:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14043 |
Actions (login required)
 |
View Item |
