Stephen W. Fesik

TL;DR: A construct for the optimized bacterial expression and purification of the MDM2 p53 binding domain and introduces a point mutation of one of the key interaction residues in the p53 peptide to weaken the protein/peptide interaction.

TL;DR: The structure and peptide affinity measurements suggest a sequence motif for peptides that bind to the top face of KLHL-12, a substrate specific adapter protein for a Cul3-Ring Ligase complex, may contribute to efforts to find small molecule ligands that can either directly inhibit the degradation of substrate proteins or be used in targeted protein degradation strategies using PROTACs.

TL;DR: The NMR structures of the complexes formed between FKBP12 and ascomcyin or C24-deoxyascomycin were very similar, suggesting that hydrogen-bonding interactions with the C24 hydroxyl moiety are not important for complex formation.

TL;DR: Measurement of 13C spin--lattice relaxation times (T1) for the two alpha, alpha-disubstituted DOM analogues confirmed theoretical predictions of very restricted conformational freedom for the dimethyl compound but more flexibility for the cyclopropane analogue.

TL;DR: In this article, the authors describe the discovery of high-affinity small-molecule ligands for TIM-3 through an NMR-based fragment screen and structure-based lead optimization.