6e5l

Crystal structure of human cellular retinol binding protein 1 in complex with abnormal-cannabidiol (abn-CBD)

spinqualitylabelsall models 6e5l, resolution 1.17Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6e5l 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 1.17Å Ligands: HVD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RET1_HUMAN Intracellular transport of retinol. Publication Abstract from PubMed Cellular retinol-binding proteins (CRBPs) facilitate the uptake and intracellular transport of vitamin A. They integrate retinoid metabolism, playing an important role in regulating the synthesis of bioactive vitamin A metabolites. Thus, CRBPs constitute potential pharmacological targets to modulate cellular retinoid status that in turn may have applications in the treatment of certain immunological, metabolic, and ocular disorders. Here we identify abnormal cannabidiol (abn-CBD) as a nonretinoid inhibitor of cellular retinol-binding protein 1 (CRBP1). X-ray crystal structures of CRBP1 in complex with abn-CBD and its derivatives revealed a distinctive mode of protein-ligand interaction and provided a molecular basis for the high affinity and selectivity of this compound. We demonstrated that abn-CBD modulates the flux of retinoids via the retinoid cycle in vivo. Furthermore, the biological activity of abn-CBD was evidenced by its ability to protect against light-induced retinal damage in Balb/cJ mice. Altogether, our findings indicate that targeting selected CRBPs with a small-molecule inhibitor can potentially lead to the development of new therapeutic agents to counteract diseases with etiologies involving imbalance in retinoid metabolism or signaling. Abnormal Cannabidiol Modulates Vitamin A Metabolism by Acting as a Competitive Inhibitor of CRBP1.,Silvaroli JA, Widjaja-Adhi MAK, Trischman T, Chelstowska S, Horwitz S, Banerjee S, Kiser PD, Blaner WS, Golczak M ACS Chem Biol. 2019 Mar 15;14(3):434-448. doi: 10.1021/acschembio.8b01070. Epub, 2019 Feb 18. PMID:30721022 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Retinol-binding protein 3D structures

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