8iy9

Structure of Niacin-GPR109A-G protein complex

spinqualitylabelsall models 8iy9, resolution 3.37Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8iy9 is a 5 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.37Å Ligands: NIO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The Hydroxycarboxylic acid receptor 2 (HCA2), also known as the niacin receptor or GPR109A, is a prototypical GPCR that plays a central role in the inhibition of lipolytic and atherogenic activities. Its activation also results in vasodilation that is linked to the side-effect of flushing associated with dyslipidemia drugs such as niacin. GPR109A continues to be a target for developing potential therapeutics in dyslipidemia with minimized flushing response. Here, we present cryo-EM structures of the GPR109A in complex with dyslipidemia drugs, niacin or acipimox, non-flushing agonists, MK6892 or GSK256073, and recently approved psoriasis drug, monomethyl fumarate (MMF). These structures elucidate the binding mechanism of agonists, molecular basis of receptor activation, and insights into biased signaling elicited by some of the agonists. The structural framework also allows us to engineer receptor mutants that exhibit G-protein signaling bias, and therefore, our study may help in structure-guided drug discovery efforts targeting this receptor. Structure-guided engineering of biased-agonism in the human niacin receptor via single amino acid substitution.,Yadav MK, Sarma P, Maharana J, Ganguly M, Mishra S, Zaidi N, Dalal A, Singh V, Saha S, Mahajan G, Sharma S, Chami M, Banerjee R, Shukla AK Nat Commun. 2024 Mar 2;15(1):1939. doi: 10.1038/s41467-024-46239-2. PMID:38431681 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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