5mei

Crystal structure of Agelastatin A bound to the 80S ribosome

spinqualitylabelsall models 5mei, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5mei is a 20 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.5Å Ligands: 7MB, MG, OHX, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RL2A_YEAST Publication Abstract from PubMed Protein synthesis plays an essential role in cell proliferation, differentiation, and survival. Inhibitors of eukaryotic translation have entered the clinic, establishing the translation machinery as a promising target for chemotherapy. A recently discovered, structurally unique marine sponge-derived brominated alkaloid, (-)-agelastatin A (AglA), possesses potent antitumor activity. Its underlying mechanism of action, however, has remained unknown. Using a systematic top-down approach, we show that AglA selectively inhibits protein synthesis. Using a high-throughput chemical footprinting method, we mapped the AglA-binding site to the ribosomal A site. A 3.5 A crystal structure of the 80S eukaryotic ribosome from S. cerevisiae in complex with AglA was obtained, revealing multiple conformational changes of the nucleotide bases in the ribosome accompanying the binding of AglA. Together, these results have unraveled the mechanism of inhibition of eukaryotic translation by AglA at atomic level, paving the way for future structural modifications to develop AglA analogs into novel anticancer agents. Inhibition of Eukaryotic Translation by the Antitumor Natural Product Agelastatin A.,McClary B, Zinshteyn B, Meyer M, Jouanneau M, Pellegrino S, Yusupova G, Schuller A, Reyes JCP, Lu J, Guo Z, Ayinde S, Luo C, Dang Y, Romo D, Yusupov M, Green R, Liu JO Cell Chem Biol. 2017 May 18;24(5):605-613.e5. doi:, 10.1016/j.chembiol.2017.04.006. Epub 2017 Apr 27. PMID:28457705 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribosome 3D structures 3D sructureseceptor for activated protein kinase C 1

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