Modulation of a conformational ensemble by a small molecule that inhibits key protein-protein interactions involved in cell adhesion.

ABSTRACT: Small molecules that regulate protein-protein interactions can be valuable drugs; however, the development of such small molecules is challenging as the molecule must interfere with an interaction that often involves a large surface area. Herein, we propose that modulating the conformational ensemble of the proteins participating in a given interaction, rather than blocking the interaction by directly binding to the interface, is a relevant strategy for interfering with a protein-protein interaction. In this study, we applied this concept to P-cadherin, a cell surface protein forming homodimers that are essential for cell-cell adhesion in various biological contexts. We first determined the crystal structure of P-cadherin with a small molecule inhibitor whose inhibitory mechanism was unkno

SUBMITTER: Senoo A 

PROVIDER: S-EPMC10443342 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature