2q3y | pdb_00002q3y

Ancestral Corticiod Receptor in Complex with DOC

spinqualitylabelsall models 2q3y, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2q3y is a 2 chain structure with sequence from Miscellaneous nucleic acid. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 1CA, GOL Related: 2q1v, 2q1h Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [NR0B2_HUMAN] Defects in NR0B2 may be associated with obesity (OBESITY) [MIM:601665]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. Function [NR0B2_HUMAN] Acts as a transcriptional regulator. Acts as a negative regulator of receptor-dependent signaling pathways. Specifically inhibits transactivation of the nuclear receptor with whom it interacts. Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated trancription complex for NEUROD1. 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 The structural mechanisms by which proteins have evolved new functions are known only indirectly. We report x-ray crystal structures of a resurrected ancestral protein-the approximately 450 million-year-old precursor of vertebrate glucocorticoid (GR) and mineralocorticoid (MR) receptors. Using structural, phylogenetic, and functional analysis, we identify the specific set of historical mutations that recapitulate the evolution of GR's hormone specificity from an MR-like ancestor. These substitutions repositioned crucial residues to create new receptor-ligand and intraprotein contacts. Strong epistatic interactions occur because one substitution changes the conformational position of another site. "Permissive" mutations-substitutions of no immediate consequence, which stabilize specific elements of the protein and allow it to tolerate subsequent function-switching changes-played a major role in determining GR's evolutionary trajectory. Crystal structure of an ancient protein: evolution by conformational epistasis.,Ortlund EA, Bridgham JT, Redinbo MR, Thornton JW Science. 2007 Sep 14;317(5844):1544-8. Epub 2007 Aug 16. PMID:17702911 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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