6IAM

Modulating Protein-Protein Interactions with Visible Light Peptide Backbone Switches

Summary for 6IAM

• Entry DOI: 10.2210/pdb6iam/pdb
• Descriptor: WD repeat-containing protein 5, SER-ALA-ARG-ALA-XY5-VAL-HIS-LEU-ARG-LYS-SER-ALA, Small ubiquitin-related modifier 5, ... (6 entities in total)
• Functional Keywords: histone modification, trimethylation at 'lys-4', epigenetic transcriptional activation, nsl complex, osteoblasts differentiation, leukemia, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 35775.73

Authors

Werel, L.,Essen, L.-O. (deposition date: 2018-11-27, release date: 2019-02-06, Last modification date: 2024-11-13)

Primary citation

Albert, L.,Penalver, A.,Djokovic, N.,Werel, L.,Hoffarth, M.,Ruzic, D.,Xu, J.,Essen, L.O.,Nikolic, K.,Dou, Y.,Vazquez, O.
Modulating Protein-Protein Interactions with Visible-Light-Responsive Peptide Backbone Photoswitches.
Chembiochem, 20:1417-1429, 2019

PubMed Abstract: Life relies on a myriad of carefully orchestrated processes, in which proteins and their direct interplay ultimately determine cellular function and disease. Modulation of this complex crosstalk has recently attracted attention, even as a novel therapeutic strategy. Herein, we describe the synthesis and characterization of two visible-light-responsive peptide backbone photoswitches based on azobenzene derivatives, to exert optical control over protein-protein interactions (PPI). The novel peptidomimetics undergo fast and reversible isomerization with low photochemical fatigue under alternatively blue-/green-light irradiation cycles. Both bind in the nanomolar range to the protein of interest. Importantly, the best peptidomimetic displays a clear difference between isomers in its protein-binding capacity and, in turn, in its potential to inhibit enzymatic activity through PPI disruption. In addition, crystal structure determination, docking and molecular dynamics calculations allow a molecular interpretation and open up new avenues in the design and synthesis of future photoswitchable PPI modulators.

PubMed: 30675988
DOI: 10.1002/cbic.201800737

Experimental method

X-RAY DIFFRACTION (1.51 Å)