5tbw

Crystal structure of chlorolissoclimide bound to the yeast 80S ribosome

spinqualitylabelsall models 5tbw, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5tbw is a 17 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 3Å Ligands: 7AL, MG, OHX, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RS18A_YEAST Located at the top of the head of the 40S subunit, it contacts several helices of the 18S rRNA (By similarity).[HAMAP-Rule:MF_01315] Publication Abstract from PubMed The lissoclimides are unusual succinimide-containing labdane diterpenoids that were reported to be potent cytotoxins. Our short semisynthesis and analogue-oriented synthesis approaches provide a series of lissoclimide natural products and analogues that expand the structure-activity relationships (SARs) in this family. The semisynthesis approach yielded significant quantities of chlorolissoclimide (CL) to permit an evaluation against the National Cancer Institute's 60-cell line panel and allowed us to obtain an X-ray co-crystal structure of the synthetic secondary metabolite with the eukaryotic 80S ribosome. Although it shares a binding site with other imide-based natural product translation inhibitors, CL engages in a particularly interesting and novel face-on halogen-pi interaction between the ligand's alkyl chloride and a guanine residue. Our analogue-oriented synthesis provides many more lissoclimide compounds, which were tested against aggressive human cancer cell lines and for protein synthesis inhibitory activity. Finally, computational modelling was used to explain the SARs of certain key compounds and set the stage for the structure-guided design of better translation inhibitors. Synthesis facilitates an understanding of the structural basis for translation inhibition by the lissoclimides.,Konst ZA, Szklarski AR, Pellegrino S, Michalak SE, Meyer M, Zanette C, Cencic R, Nam S, Voora VK, Horne DA, Pelletier J, Mobley DL, Yusupova G, Yusupov M, Vanderwal CD Nat Chem. 2017 Nov;9(11):1140-1149. doi: 10.1038/nchem.2800. Epub 2017 Jul 3. PMID:29064494 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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