4u4z
From Proteopedia
Crystal structure of Phyllanthoside bound to the yeast 80S ribosome
Structural highlights
FunctionSTM1_YEAST Binds specifically G4 quadruplex (these are four-stranded right-handed helices, stabilized by guanine base quartets) and purine motif triplex (characterized by a third, antiparallel purine-rich DNA strand located within the major groove of a homopurine stretch of duplex DNA) nucleic acid structures. These structures may be present at telomeres or in rRNAs. Acts with CDC13 to control telomere length homeostasis. Involved in the control of the apoptosis-like cell death.[1] Publication Abstract from PubMedThe ribosome is a molecular machine responsible for protein synthesis and a major target for small-molecule inhibitors. Compared to the wealth of structural information available on ribosome-targeting antibiotics in bacteria, our understanding of the binding mode of ribosome inhibitors in eukaryotes is currently limited. Here we used X-ray crystallography to determine 16 high-resolution structures of 80S ribosomes from Saccharomyces cerevisiae in complexes with 12 eukaryote-specific and 4 broad-spectrum inhibitors. All inhibitors were found associated with messenger RNA and transfer RNA binding sites. In combination with kinetic experiments, the structures suggest a model for the action of cycloheximide and lactimidomycin, which explains why lactimidomycin, the larger compound, specifically targets the first elongation cycle. The study defines common principles of targeting and resistance, provides insights into translation inhibitor mode of action and reveals the structural determinants responsible for species selectivity which could guide future drug development. Structural basis for the inhibition of the eukaryotic ribosome.,Garreau de Loubresse N, Prokhorova I, Holtkamp W, Rodnina MV, Yusupova G, Yusupov M Nature. 2014 Sep 25;513(7519):517-22. doi: 10.1038/nature13737. Epub 2014 Sep 10. PMID:25209664[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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