7e2e
Crystal structure of the Estrogen-Related Receptor alpha (ERRalpha) ligand-binding domain (LBD) in complex with an agonist DS45500853 and a PGC-1alpha peptide
Structural highlights
FunctionERR1_HUMAN Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism.[1] [2] [3] [4] [5] Publication Abstract from PubMedA novel class of estrogen-related receptor alpha (ERRalpha) agonists has been discovered. A structure-activity relationship study of high-throughput screening hits 1 and 2 led to the discovery of benzimidazole 3d (DS20362725) and acetophenone analogue 5c (DS45500853). The X-ray crystal structure of the ERRalpha ligand-binding domain in complex with 5c and PGC-1alpha coactivator peptide revealed conformational changes in the ligand-binding pocket to accommodate 5c and the key interaction between the protein and ligand. Since both analogues avoided PPARgamma transcriptional activity, they can be useful tool compounds for investigating biological ERRalpha functions. Discovery of a Novel Class of ERRalpha Agonists.,Shinozuka T, Ito S, Kimura T, Izumi M, Wakabayashi K ACS Med Chem Lett. 2021 Apr 21;12(5):817-821. doi: , 10.1021/acsmedchemlett.1c00100. eCollection 2021 May 13. PMID:34055231[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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