5ogb

Human Cellular Retinoic Acid Binding Protein II (CRABPII) with bound synthetic retinoid DC360.

spinqualitylabelsall models 5ogb, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ogb 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 1.8Å Ligands: 9U5 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RABP2_HUMAN Transports retinoic acid to the nucleus. Regulates the access of retinoic acid to the nuclear retinoic acid receptors. Publication Abstract from PubMed Retinoids, such as all- trans-retinoic acid (ATRA), are endogenous signaling molecules derived from vitamin A that influence a variety of cellular processes through mediation of transcription events in the cell nucleus. Because of these wide-ranging and powerful biological activities, retinoids have emerged as therapeutic candidates of enormous potential. However, their use has been limited, to date, due to a lack of understanding of the complex and intricate signaling pathways that they control. We have designed and synthesized a family of synthetic retinoids that exhibit strong, intrinsic, solvatochromatic fluorescence as multifunctional tools to interrogate these important biological activities. We utilized the unique photophysical characteristics of these fluorescent retinoids to develop a novel in vitro fluorometric binding assay to characterize and quantify their binding to their cellular targets, including cellular retinoid binding protein II (CRABPII). The dihydroquinoline retinoid, DC360, exhibited particularly strong binding ( Kd = 34.0 +/- 2.5 nM), and we further used X-ray crystallography to determine the structure of the DC360-CRABPII complex to 1.8 A, which showed that DC360 occupies the known hydrophobic retinoid binding pocket. Finally, we used confocal fluorescence microscopy to image the cellular behavior of the compounds in cultured human epithelial cells, highlighting a fascinating nuclear localization, and used RNA sequencing to confirm that the compounds regulate cellular processes similar to those of ATRA. We anticipate that the unique properties of these fluorescent retinoids can now be used to cast new light on the vital and highly complex retinoid signaling pathway. Fluorescent Retinoic Acid Analogues as Probes for Biochemical and Intracellular Characterization of Retinoid Signaling Pathways.,Chisholm DR, Tomlinson CWE, Zhou GL, Holden C, Affleck V, Lamb R, Newling K, Ashton P, Valentine R, Redfern C, Erostyak J, Makkai G, Ambler CA, Whiting A, Pohl E ACS Chem Biol. 2019 Mar 15;14(3):369-377. doi: 10.1021/acschembio.8b00916. Epub, 2019 Feb 13. PMID:30707838 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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