5Y7W

Crystal structure of the Nco-A1 PAS-B domain with YL-2

Summary for 5Y7W

• Entry DOI: 10.2210/pdb5y7w/pdb
• Descriptor: Nuclear receptor coactivator 1, YL-2 peptide (3 entities in total)
• Functional Keywords: inflammatory allergic diseases and cancers, nuclear receptor coactivator 1, stapled peptide, transcription-inihibitor complex, transcription/inihibitor
• Biological source: Mus musculus (Mouse); More
• Cellular location: Nucleus : P70365
• Total number of polymer chains: 4
• Total formula weight: 32673.50

Authors

Lee, Y.J.,Yoon, H.S.,Lee, J.H.,Bae, J.H.,Song, J.Y.,Lim, H.S. (deposition date: 2017-08-18, release date: 2017-11-15, Last modification date: 2024-10-16)

Primary citation

Lee, Y.,Yoon, H.,Hwang, S.M.,Shin, M.K.,Lee, J.H.,Oh, M.,Im, S.H.,Song, J.,Lim, H.S.
Targeted Inhibition of the NCOA1/STAT6 Protein-Protein Interaction
J. Am. Chem. Soc., 139:16056-16059, 2017

PubMed Abstract: The complex formation between transcription factors (TFs) and coactivator proteins is required for transcriptional activity, and thus disruption of aberrantly activated TF/coactivator interactions could be an attractive therapeutic strategy. However, modulation of such protein-protein interactions (PPIs) has proven challenging. Here we report a cell-permeable, proteolytically stable, stapled helical peptide directly targeting nuclear receptor coactivator 1 (NCOA1), a coactivator required for the transcriptional activity of signal transducer and activator of transcription 6 (STAT6). We demonstrate that this stapled peptide disrupts the NCOA1/STAT6 complex, thereby repressing STAT6-mediated transcription. Furthermore, we solved the first crystal structure of a stapled peptide in complex with NCOA1. The stapled peptide therefore represents an invaluable chemical probe for understanding the precise role of the NCOA1/STAT6 interaction and an excellent starting point for the development of a novel class of therapeutic agents.

PubMed: 29090910
DOI: 10.1021/jacs.7b08972

Experimental method

X-RAY DIFFRACTION (2.25 Å)