4n73 | pdb_00004n73

Crystal structure of the ligand binding domain (LBD) of REV-ERB beta bound to Cobalt Protoporphyrin IX

spinqualitylabelsall models 4n73, resolution 1.87Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4n73 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 1.8662Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NR1D2_HUMAN Binds to the sequences 5'-AATGTAGGTCA-3' and 5'-ATAACTAGGTCA-3'. Acts as a potent competitive repressor of ROR alpha function (By similarity). Publication Abstract from PubMed REV-ERBalpha and REV-ERBbeta are members of the nuclear receptor (NR) superfamily of ligand regulated transcription factors that play important roles in regulation of circadian physiology, metabolism and immune function. Although the REV-ERBs were originally characterized as orphan receptors recent studies have demonstrated that they function as receptors for heme. Here, we demonstrate that cobalt protoporphyrin IX (CoPP) and zinc protoporphyrin IX (ZnPP) are ligands that bind directly to the REV-ERBs. However, instead of mimicking the agonist action of heme, CoPP and ZnPP function as antagonists of REV-ERB function. This was unexpected since the only distinction between these ligands is the metal ion that is coordinated. To understand the structural basis by which REV-ERBbeta can differentiate between a porphyrin agonist and antagonist, we characterized the interaction between REV-ERBbeta with heme, CoPP and ZnPP using biochemical and structural approaches, including x-ray crystallography and NMR. The crystal structure of CoPP-bound REV-ERBbeta indicates only minor conformational changes induced by CoPP compared to heme, including the porphyrin ring of CoPP, which adopts a planar conformation as opposed to the puckered conformation observed in the heme-bound REV-ERBbeta crystal structure. Thus subtle changes in the porphyrin metal center and ring conformation may influence the agonist vs. antagonist action of porphyrins, and when considered with other studies suggest that gas binding to the iron metal center heme may drive alterations in REV-ERB activity. Structure of REV-ERBbeta Ligand-Binding Domain Bound to a Porphyrin Antagonist.,Matta-Camacho E, Banerjee S, Hughes TS, Solt LA, Wang Y, Burris TP, Kojetin DJ J Biol Chem. 2014 May 28. pii: jbc.M113.545111. PMID:24872411 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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