7NN2

Crystal structure of 14-3-3 sigma in complex with 13mer Amot-p130 peptide and fragment 41

Summary for 7NN2

• Entry DOI: 10.2210/pdb7nn2/pdb
• Descriptor: 14-3-3 protein sigma, Amot-p130 phosphopeptide (pS175), 7-(6-azanyl-5-methyl-pyridin-2-yl)-1-benzothiophene-2-carboximidamide, ... (6 entities in total)
• Functional Keywords: protein-peptide complex fragment soaking, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 30211.23

Authors

Centorrino, F.,Ottmann, C. (deposition date: 2021-02-24, release date: 2022-01-12, Last modification date: 2024-11-06)

Primary citation

Centorrino, F.,Andlovic, B.,Cossar, P.,Brunsveld, L.,Ottmann, C.
Fragment-based exploration of the 14-3-3/Amot-p130 interface.
Curr Res Struct Biol, 4:21-28, 2022

PubMed Abstract: The modulation of protein-protein interactions (PPIs) has developed into a well-established field of drug discovery. Despite the advances achieved in the field, many PPIs are still deemed as ' targets and the design of PPIs stabilizers remains a significant challenge. The application of fragment-based methods for the identification of drug leads and to evaluate the ' of the desired protein target has seen a remarkable development in recent years. In this study, we explore the molecular characteristics of the 14-3-3/Amot-p130 PPI and the conceptual possibility of targeting this interface using X-ray crystallography fragment-based screening. We report the first structural elucidation of the 14-3-3 binding motif of Amot-p130 and the characterization of the binding mode and affinities involved. We made use of fragments to probe the ' of the 14-3-3/Amot-p130 composite binding pocket. Here we disclose initial hits with promising stabilizing activity and an early-stage selectivity toward the Amot-p130 motifs over other representatives 14-3-3 partners. Our findings highlight the potential of using fragments to characterize and explore proteins' surfaces and might provide a starting point toward the development of small molecules capable of acting as .

PubMed: 35036934
DOI: 10.1016/j.crstbi.2021.12.003

Experimental method

X-RAY DIFFRACTION (1.8 Å)