8D8I

Crystal structure of Reverb alpha in complex with synthetic agonist

Summary for 8D8I

• Entry DOI: 10.2210/pdb8d8i/pdb
• Descriptor: Nuclear receptor subfamily 1 group D member 1, Nuclear receptor corepressor 1, (4S)-6-[([1,1'-biphenyl]-2-yl)oxy]-3-chloro[1,2,4]triazolo[4,3-b]pyridazine, ... (4 entities in total)
• Functional Keywords: rev-erb, nuclear receptor, agonist, transcription
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 29093.50

Authors

Ronin, C.,Ciesielski, F.,Hegazy, L.,Burris, P.T. (deposition date: 2022-06-08, release date: 2022-12-14, Last modification date: 2024-04-03)

Primary citation

Murray, M.H.,Valfort, A.C.,Koelblen, T.,Ronin, C.,Ciesielski, F.,Chatterjee, A.,Veerakanellore, G.B.,Elgendy, B.,Walker, J.K.,Hegazy, L.,Burris, T.P.
Structural basis of synthetic agonist activation of the nuclear receptor REV-ERB.
Nat Commun, 13:7131-7131, 2022

PubMed Abstract: The nuclear receptor REV-ERB plays an important role in a range of physiological processes. REV-ERB behaves as a ligand-dependent transcriptional repressor and heme has been identified as a physiological agonist. Our current understanding of how ligands bind to and regulate transcriptional repression by REV-ERB is based on the structure of heme bound to REV-ERB. However, porphyrin (heme) analogues have been avoided as a source of synthetic agonists due to the wide range of heme binding proteins and potential pleotropic effects. How non-porphyrin synthetic agonists bind to and regulate REV-ERB has not yet been defined. Here, we characterize a high affinity synthetic REV-ERB agonist, STL1267, and describe its mechanism of binding to REV-ERB as well as the method by which it recruits transcriptional corepressor both of which are unique and distinct from that of heme-bound REV-ERB.

PubMed: 36414641
DOI: 10.1038/s41467-022-34892-4

Experimental method

X-RAY DIFFRACTION (2.504 Å)