2e2r

Crystal structure of human estrogen-related receptor gamma ligand binding domain complex with bisphenol A

spinqualitylabelsall models 2e2r, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2e2r is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.6Å Ligands: 2OH, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ERR3_HUMAN Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Many lines of evidence reveal that bisphenol A (BPA) functions at very low doses as an endocrine disruptor. The human estrogen-related receptor gamma (ERR gamma) behaves as a constitutive activator of transcription, although the endogenous ligand is unknown. We have recently demonstrated that BPA binds strongly to ERR gamma (K(D) = 5.5 nM), but not to the estrogen receptor (ER). BPA preserves the ERR gamma's basal constitutive activity, and protects the selective ER modulator 4-hydroxytamoxifen from its deactivation of ERR gamma. In order to shed light on a molecular mechanism, we carried out the X-ray analysis of crystal structure of the ERR gamma ligand-binding domain (LBD) complexed with BPA. BPA binds to the receptor cavity without changing any internal structures of the pocket of the ERR gamma-LBD apo form. The hydrogen bonds of two phenol-hydroxyl groups, one with both Glu275 and Arg316, the other with Asn346, anchor BPA in the pocket, and surrounding hydrophobic bonds, especially with Tyr326, complete BPA's strong binding. Maintaining the 'activation helix' (helix 12) in an active conformation would as a result preserve receptor constitutive activity. Our results present the first evidence that the nuclear receptor forms complexes with the endocrine disruptor, providing detailed molecular insight into the interaction features. Structural evidence for endocrine disruptor bisphenol A binding to human nuclear receptor ERR gamma.,Matsushima A, Kakuta Y, Teramoto T, Koshiba T, Liu X, Okada H, Tokunaga T, Kawabata S, Kimura M, Shimohigashi Y J Biochem. 2007 Oct;142(4):517-24. Epub 2007 Aug 30. PMID:17761695 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Estrogen-related receptor 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA