Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline.
Journal, issue, pages	Nat Commun, Vol. 15, Issue 1, Page 5481, Year 2024
Publish date	Jun 28, 2024
Authors	Xiang Li / Mengjiao Wang / Timo Denk / Robert Buschauer / Yi Li / Roland Beckmann / Jingdong Cheng /
PubMed Abstract	Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, ...Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, even though it is also cytotoxic for human cells, the molecular mechanism of its inhibition remains unclear. Here, we present cryo-EM structures of tigecycline-bound human mitochondrial 55S, 39S, cytoplasmic 80S and yeast cytoplasmic 80S ribosomes. We find that at clinically relevant concentrations, tigecycline effectively targets human 55S mitoribosomes, potentially, by hindering A-site tRNA accommodation and by blocking the peptidyl transfer center. In contrast, tigecycline does not bind to human 80S ribosomes under physiological concentrations. However, at high tigecycline concentrations, in addition to blocking the A-site, both human and yeast 80S ribosomes bind tigecycline at another conserved binding site restricting the movement of the L1 stalk. In conclusion, the observed distinct binding properties of tigecycline may guide new pathways for drug design and therapy.
External links	Nat Commun / PubMed:38942792 / PubMed Central
Methods	EM (single particle)
Resolution	2.0 - 3.6 Å
Structure data	36836 8k2a EMDB-36836, PDB-8k2a: Cryo-EM structure of the human 55S mitoribosome with Tigecycline Method: EM (single particle) / Resolution: 2.9 Å 36837 8k2b EMDB-36837, PDB-8k2b: Cryo-EM structure of the human 39S mitoribosome with Tigecycline Method: EM (single particle) / Resolution: 3.4 Å 36838 8k2c EMDB-36838, PDB-8k2c: Cryo-EM structure of the human 80S ribosome with Tigecycline Method: EM (single particle) / Resolution: 2.4 Å 36839 8k2d EMDB-36839, PDB-8k2d: Cryo-EM structure of the yeast 80S ribosome with tigecycline, eEF2, Stm1 and eIF5A Method: EM (single particle) / Resolution: 3.2 Å 36945 8k82 EMDB-36945, PDB-8k82: Cryo-EM structure of the yeast 80S ribosome with tigecycline, Not5 and P-site tRNA Method: EM (single particle) / Resolution: 3.0 Å 38629 8xsx EMDB-38629, PDB-8xsx: Cryo-EM structure of the human 80S ribosome with Tigecycline, E-tRNA, SERBP1 and eEF2 Method: EM (single particle) / Resolution: 2.4 Å 38630 8xsy EMDB-38630, PDB-8xsy: Cryo-EM structure of the human 80S ribosome with Tigecycline, e-tRNA and CCDC124 (40S head Swivelled) Method: EM (single particle) / Resolution: 3.0 Å 38631 8xsz EMDB-38631, PDB-8xsz: Cryo-EM structure of the human 80S ribosome with Tigecycline, E-tRNA and P-tRNA Method: EM (single particle) / Resolution: 3.2 Å 38632 8xt0 EMDB-38632, PDB-8xt0: Cryo-EM structure of the human 55S mitoribosome with 5um Tigecycline Method: EM (single particle) / Resolution: 3.2 Å 38633 8xt1 EMDB-38633, PDB-8xt1: Cryo-EM structure of the human 39S mitoribosome with 5uM Tigecycline Method: EM (single particle) / Resolution: 3.1 Å 38634 8xt2 EMDB-38634, PDB-8xt2: Cryo-EM structure of the human 55S mitoribosome with 10uM Tigecycline Method: EM (single particle) / Resolution: 3.3 Å 38635 8xt3 EMDB-38635, PDB-8xt3: Cryo-EM structure of the human 39S mitoribosome with 10uM Tigecycline Method: EM (single particle) / Resolution: 3.1 Å EMDB-38636: Cryo-EM structure of the human 55S mitoribosome with 5uM Tigecycline (focusing on 39S ribosome) Method: EM (single particle) / Resolution: 3.1 Å EMDB-38637: Cryo-EM structure of the human 55S mitoribosome with 5uM Tigecycline (focusing on 28S ribosome head) Method: EM (single particle) / Resolution: 3.4 Å EMDB-38638: Cryo-EM structure of the human 55S mitoribosome with 10uM Tigecycline (focusing on 39S ribosome) Method: EM (single particle) / Resolution: 3.2 Å EMDB-38639: Cryo-EM structure of the human 55S mitoribosome with 10uM Tigecycline (focusing on 28S ribosome head) Method: EM (single particle) / Resolution: 3.6 Å 39455 8yoo EMDB-39455, PDB-8yoo: Cryo-EM structure of the human 80S ribosome with 100 um Tigecycline Method: EM (single particle) / Resolution: 2.0 Å 39456 8yop EMDB-39456, PDB-8yop: Cryo-EM structure of the human 80S ribosome with 4 um Tigecycline Method: EM (single particle) / Resolution: 2.2 Å
Chemicals	ChemComp-MG: Unknown entry ChemComp-T1C: TIGECYCLINE / medication, antibioticYM ChemComp-ZN: Unknown entry ChemComp-GDP: GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying moleculeYM ChemComp-PNS: 4'-PHOSPHOPANTETHEINE ChemComp-SPD: SPERMIDINE ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM
Source	homo sapiens (human) saccharomyces cerevisiae (brewer's yeast)
Keywords	RIBOSOME / 55S mitoribosome / Tigecycline / antibiotic / 39S mitoribosome / 80S ribosome / eEF2 / SERBP1 / CCDC124