8C30

Crystal structure of 14-3-3 in complex with PyrinpS242 and a protein/peptide interface fragment

This is a non-PDB format compatible entry.

Summary for 8C30

• Entry DOI: 10.2210/pdb8c30/pdb
• Descriptor: 14-3-3 protein sigma, Pyrin, N-[3-(aminomethyl)phenyl]acetamide, ... (7 entities in total)
• Functional Keywords: protein-peptide interaction, phosphorylation reader protein, immunology, scaffolding, intrinsic disorder motif, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 28685.68

Authors

Lau, R.,Ottmann, C. (deposition date: 2022-12-23, release date: 2024-01-10, Last modification date: 2025-01-22)

Primary citation

Lau, R.,Hann, M.M.,Ottmann, C.
Crystal structure and ligandability of the 14-3-3/pyrin interface.
Biochem.Biophys.Res.Commun., 651:1-7, 2023

PubMed Abstract: Overactivation of Pyrin is the cause of the inflammatory diseases Mediterranean Fever and Pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). Binding of 14-3-3 proteins reduces the pro-inflammatory activity of Pyrin, hence small molecules that stabilize the Pyrin/14-3-3 complex could convey an anti-inflammatory effect. We have solved the atomic resolution crystal structures of phosphorylated peptides derived from PyrinpS208 and PyrinpS242 - the two principle 14-3-3 binding sites in Pyrin - in complex with 14-3-3 and analyzed the ligandability of these protein-peptide interfaces by crystal-based fragment soaking. The complex between 14-3-3 and PyrinpS242 appears to be much more amenable for small-molecule binding than that of 14-3-3/PyrinpS208. Consequently, only for the 14-3-3/PyrinpS242 complex could we find an interface-binding fragment, validating protein crystallography and fragment soaking as a method to evaluate the ligandability of protein surfaces.

PubMed: 36774661
DOI: 10.1016/j.bbrc.2023.02.013

Experimental method

X-RAY DIFFRACTION (1.4 Å)