5j4c | pdb_00005j4c

Crystal structure of the Thermus thermophilus 70S ribosome in complex with cisplatin (soaked) and bound to mRNA and A-, P- and E-site tRNAs at 2.8A resolution

spinqualitylabelsall models 5j4c, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5j4c is a 20 chain structure with sequence from Thermus thermophilus HB8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: 0TD, 2MA, 2MG, 2MU, 4OC, 4SU, 5MC, 5MU, 7MG, CPT, K, M2G, MA6, MG, MIA, OMG, PSU, SF4, UR3, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RL17_THET8 Publication Abstract from PubMed Cisplatin is a widely prescribed anticancer drug, which triggers cell death by covalent binding to a broad range of biological molecules. Among cisplatin targets, cellular RNAs remain the most poorly characterized molecules. Although cisplatin was shown to inactivate essential RNAs, including ribosomal, spliceosomal and telomeric RNAs, cisplatin binding sites in most RNA molecules are unknown, and therefore it remains challenging to study how modifications of RNA by cisplatin contributes to its toxicity. Here we report a 2.6A-resolution X-ray structure of cisplatin-modified 70S ribosome, which describes cisplatin binding to the ribosome and provides the first nearly atomic model of cisplatin-RNA complex. We observe nine cisplatin molecules bound to the ribosome and reveal consensus structural features of the cisplatin-binding sites. Two of the cisplatin molecules modify conserved functional centers of the ribosome-the mRNA-channel and the GTPase center. In the mRNA-channel, cisplatin intercalates between the ribosome and the messenger RNA, suggesting that the observed inhibition of protein synthesis by cisplatin is caused by impaired mRNA-translocation. Our structure provides an insight into RNA targeting and inhibition by cisplatin, which can help predict cisplatin-binding sites in other cellular RNAs and design studies to elucidate a link between RNA modifications by cisplatin and cisplatin toxicity. Insights into RNA binding by the anticancer drug cisplatin from the crystal structure of cisplatin-modified ribosome.,Melnikov SV, Soll D, Steitz TA, Polikanov YS Nucleic Acids Res. 2016 Apr 13. pii: gkw246. PMID:27079977 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribosomal protein THX 3D structures Ribosome 3D structures

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