5i4l

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Crystal structure of Amicoumacin A bound to the yeast 80S ribosome

Structural highlights

5i4l 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 3.1Å
Ligands:MG, OHX, UAM, ZN
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RSSA1_YEAST Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits.[1] [2]

Publication Abstract from PubMed

Amicoumacin A is an antibiotic that was recently shown to target bacterial ribosomes. It affects translocation and provides an additional contact interface between the ribosomal RNA and mRNA. The binding site of amicoumacin A is formed by universally conserved nucleotides of rRNA. In this work, we showed that amicoumacin A inhibits translation in yeast and mammalian systems by affecting translation elongation. We determined the structure of the amicoumacin A complex with yeast ribosomes at a resolution of 3.1 A. Toxicity measurement demonstrated that human cancer cell lines are more susceptible to the inhibition by this compound as compared to non-cancerous ones. This might be used as a starting point to develop amicoumacin A derivatives with clinical value.

Amicoumacin A induces cancer cell death by targeting the eukaryotic ribosome.,Prokhorova IV, Akulich KA, Makeeva DS, Osterman IA, Skvortsov DA, Sergiev PV, Dontsova OA, Yusupova G, Yusupov MM, Dmitriev SE Sci Rep. 2016 Jun 14;6:27720. doi: 10.1038/srep27720. PMID:27296282[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
5 reviews cite this structure
Antibiotics from Gram-negative bacteria: a comprehensive overview and selected biosynthetic highlights.
Masschelein et al. (2017)
4 more
13 other articles
No citations found

See Also

References

  1. ↑ Ford CL, Randal-Whitis L, Ellis SR. Yeast proteins related to the p40/laminin receptor precursor are required for 20S ribosomal RNA processing and the maturation of 40S ribosomal subunits. Cancer Res. 1999 Feb 1;59(3):704-10. PMID:9973221
  2. ↑ Tabb-Massey A, Caffrey JM, Logsden P, Taylor S, Trent JO, Ellis SR. Ribosomal proteins Rps0 and Rps21 of Saccharomyces cerevisiae have overlapping functions in the maturation of the 3' end of 18S rRNA. Nucleic Acids Res. 2003 Dec 1;31(23):6798-805. PMID:14627813
  3. ↑ Prokhorova IV, Akulich KA, Makeeva DS, Osterman IA, Skvortsov DA, Sergiev PV, Dontsova OA, Yusupova G, Yusupov MM, Dmitriev SE. Amicoumacin A induces cancer cell death by targeting the eukaryotic ribosome. Sci Rep. 2016 Jun 14;6:27720. doi: 10.1038/srep27720. PMID:27296282 doi:http://dx.doi.org/10.1038/srep27720

Contents


PDB ID 5i4l

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