Kneuttinger, Andrea C. and Straub, Kristina and Bittner, Philipp and Simeth, Nadja A. and Bruckmann, Astrid and Busch, Florian and Rajendran, Chitra and Hupfeld, Enrico and Wysocki, Vicki H. and Horinek, Dominik and Koenig, Burkhard and Merkl, Rainer and Sterner, Reinhard (2019) Light Regulation of Enzyme Allostery through Photo-responsive Unnatural Amino Acids. CELL CHEMICAL BIOLOGY, 26 (11). 1501-+. ISSN 2451-9448,
Full text not available from this repository. (Request a copy)Abstract
Imidazole glycerol phosphate synthase (ImGPS) is an allosteric bienzyme complex in which substrate binding to the synthase subunit HisF stimulates the glutaminase subunit HisH. To control this stimulation with light, we have incorporated the photo-responsive unnatural amino acids phenylalanine-4'-azobenzene (AzoF), o-nitropiperonyl-O-tyrosine (NPY), and methyl-o-nitropiperonyllysine (mNPK) at strategic positions of HisF. The light-mediated isomerization of AzoF at position 55 (fS55AzoF(E) <-> fS55AzoF(Z)) resulted in a reversible 10-fold regulation of HisH activity. The light-mediated decaging of NPY at position 39 (fY39NPY -> fY39) and of mNPK at position 99 (fK99mNPK -> fK99) led to a 4- to 6-fold increase of HisH activity. Molecular dynamics simulations explained how the unnatural amino acids interfere with the allosteric machinery of ImGPS and revealed additional aspects of HisH stimulation in wild-type ImGPS. Our findings show that unnatural amino acids can be used as a powerful tool for the spatio-temporal control of a central metabolic enzyme complex by light.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLYCEROL PHOSPHATE SYNTHASE; OPTICAL CONTROL; GLUTAMINE AMIDOTRANSFERASE; STRUCTURE VALIDATION; MOLECULAR-DYNAMICS; PROTECTING GROUPS; PROTEIN FUNCTION; BIOCATALYSIS; ACTIVATION; REDUCTION; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Mar 2020 09:01 |
| Last Modified: | 24 Mar 2020 09:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25813 |
Actions (login required)
 |
View Item |
