PH-Dependent Conformational Changes in Grb2 Monomer Reveal Different Binding Sites for Coumarin: An Insight for Small Molecule Drug Discovery.

ABSTRACT: Growth factor receptor-bound protein 2 (Grb2) is an essential adaptor protein that mediates activation of the RAS/mitogen-activated protein kinase (MAPK) signaling cascade by linking receptor tyrosine kinase to the guanine nucleotide exchange factor SOS (Son of Sevenless). Grb2 exists in a dynamic monomer-dimer equilibrium, with only the monomer competent for signaling. Dysregulation of this pathway is common in cancer, making Grb2 a compelling therapeutic target. Coumarin, a plant-derived compound with reported anticarcinogenic activity, was previously shown to bind the SH2 domain of dimeric Grb2. Here, we investigated the interaction between coumarin and the monomeric form of Grb2 under two physiologically relevant pH conditions (7 and 8), corresponding to healthy and cancer cell environ

SUBMITTER: Casteluci G 

PROVIDER: S-EPMC12917664 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature