5on6

Crystal structure of haemanthamine bound to the 80S ribosome

spinqualitylabelsall models 5on6, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5on6 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 3.1000023Å Ligands: GOL, MG, OHX, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RL2A_YEAST Publication Abstract from PubMed Alkaloids isolated from the Amaryllidaceae plants have potential as therapeutics for treating human diseases. Haemanthamine has been studied as a novel anticancer agent due to its ability to overcome cancer cell resistance to apoptosis. Biochemical experiments have suggested that hemanthamine targets the ribosome. However, a structural characterization of its mechanism has been missing. Here we present the 3.1 A resolution X-ray structure of haemanthamine bound to the Saccharomyces cerevisiae 80S ribosome. This structure reveals that haemanthamine targets the A-site cleft on the large ribosomal subunit rearranging rRNA to halt the elongation phase of translation. Furthermore, we provide evidence that haemanthamine and other Amaryllidaceae alkaloids also inhibit specifically ribosome biogenesis, triggering nucleolar stress response and leading to p53 stabilization in cancer cells. Together with a computer-aided interpretation of existing structure-activity relationships of Amaryllidaceae alkaloids congeners, we provide a rationale for designing molecules with enhanced potencies and reduced toxicities. The Amaryllidaceae Alkaloid Haemanthamine Binds the Eukaryotic Ribosome to Repress Cancer Cell Growth.,Pellegrino S, Meyer M, Zorbas C, Bouchta SA, Saraf K, Pelly SC, Yusupova G, Evidente A, Mathieu V, Kornienko A, Lafontaine DLJ, Yusupov M Structure. 2018 Feb 3. pii: S0969-2126(18)30009-1. doi:, 10.1016/j.str.2018.01.009. PMID:29429877 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribosome 3D structures

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