4q0a

Vitamin D Receptor complex with lithocholic acid

spinqualitylabelsall models 4q0a, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4q0a is a 2 chain structure with sequence from Brachidanio rerio. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 4OA Related: 2hc4, 2hcd Gene: vdra, nr1i1a, vdr (Brachidanio rerio) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [NCOA2_HUMAN] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation. Function [VDRA_DANRE] Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Plays a central role in calcium homeostasis. [NCOA2_HUMAN] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues. Publication Abstract from PubMed The vitamin D receptor (VDR), an endocrine nuclear receptor for 1alpha,25-dihydroxyvitamin D3, acts also as a bile acid sensor by binding lithocholic acid (LCA). The crystal structure of the zebrafish VDR ligand binding domain in complex with LCA and the SRC-2 coactivator peptide reveals the binding of two LCA molecules by VDR. One LCA binds to the canonical ligand-binding pocket, and the second one, which is not fully buried, is anchored to a site located on the VDR surface. Despite the low affinity of the alternative site, the binding of the second molecule promotes stabilization of the active receptor conformation. Biological activity assays, structural analysis, and molecular dynamics simulations indicate that the recognition of two ligand molecules is crucial for VDR agonism by LCA. The unique binding mode of LCA provides clues for the development of new chemical compounds that target alternative binding sites for therapeutic applications. Structural insights into the molecular mechanism of vitamin d receptor activation by lithocholic Acid involving a new mode of ligand recognition.,Belorusova AY, Eberhardt J, Potier N, Stote RH, Dejaegere A, Rochel N J Med Chem. 2014 Jun 12;57(11):4710-9. doi: 10.1021/jm5002524. Epub 2014 May 21. PMID:24818857 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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