: / : / Ribosomal protein L37, mitochondrial / Ribosomal protein L55, mitochondrial / Mitochondrial ribosomal protein L48 / 39S ribosomal protein L40, mitochondrial / Mitochondrial ribosomal protein L55 superfamily / Mitochondrial ribosomal protein L37 / Mitochondrial ribosomal protein L55 / Mitochondrial ribosomal protein L46 NUDIX ...: / : / Ribosomal protein L37, mitochondrial / Ribosomal protein L55, mitochondrial / Mitochondrial ribosomal protein L48 / 39S ribosomal protein L40, mitochondrial / Mitochondrial ribosomal protein L55 superfamily / Mitochondrial ribosomal protein L37 / Mitochondrial ribosomal protein L55 / Mitochondrial ribosomal protein L46 NUDIX / Ribosomal protein S30, mitochondrial / Ribosomal protein L53, mitochondrial / 39S ribosomal protein L53/MRP-L53 / 39S ribosomal protein L42, mitochondrial / Mitochondrial 28S ribosomal protein S32 / Ribosomal protein L28/L40, mitochondrial / Mitochondrial ribosomal protein L28 / Ribosomal protein 63, mitochondrial / Growth arrest/ DNA-damage-inducible protein-interacting protein 1 / Ribosomal protein L51, mitochondrial / Growth arrest and DNA-damage-inducible proteins-interacting protein 1 / Mitochondrial ribosomal subunit / Mitochondrial ribosome protein 63 / Ribosomal protein L37/S30 / Growth arrest and DNA damage-inducible proteins-interacting protein 1 domain superfamily / : / : / Mitochondrial 28S ribosomal protein S30 (PDCD9) / 39S ribosomal protein L52, mitochondrial / : / Mitoribosomal protein mL52 / Ribosomal protein L35, mitochondrial / MRPL44, double-stranded RNA binding domain / : / Tim44-like domain / Tim44-like domain / Tim44 / : / Ribosomal protein L49/IMG2 / Mitochondrial large subunit ribosomal protein (Img2) / Ribosomal protein L46, N-terminal / 39S mitochondrial ribosomal protein L46 / Ribosomal protein L50, mitochondria / Ribosomal protein L27/L41, mitochondrial / : / Mitochondrial ribosomal protein L27 / Ribosomal subunit 39S / 39S ribosomal protein L46, mitochondrial / 39S ribosomal protein L43/54S ribosomal protein L51 / Ribosomal protein L47, mitochondrial / MRP-L47 superfamily, mitochondrial / Mitochondrial 39-S ribosomal protein L47 (MRP-L47) / Phosphatidylethanolamine-binding protein / Phosphatidylethanolamine-binding protein / Phosphatidylethanolamine-binding protein, eukaryotic / PEBP-like superfamily / Threonyl/alanyl tRNA synthetase, class II-like, putative editing domain superfamily / TGS domain profile. / TGS / TGS-like / Peptide chain release factor class I / RF-1 domain / Ribonuclease III, endonuclease domain superfamily / Double stranded RNA-binding domain (dsRBD) profile. / Double-stranded RNA-binding domain / : / Ribosomal protein/NADH dehydrogenase domain / Mitochondrial ribosomal protein L51 / S25 / CI-B8 domain / Mitochondrial ribosomal protein L51 / S25 / CI-B8 domain / Beta-grasp domain superfamily / NTF2-like domain superfamily / NUDIX hydrolase-like domain superfamily / Ribosomal protein L11, bacterial-type / Ribosomal protein L10-like domain superfamily / Ribosomal protein L10 / Ribosomal protein L10P / Ribosomal protein L11, N-terminal / Ribosomal protein L11, N-terminal domain / Ribosomal protein L11/L12 / Ribosomal protein L11, C-terminal / Ribosomal protein L11, C-terminal domain superfamily / Ribosomal protein L11/L12, N-terminal domain superfamily / Ribosomal protein L11, RNA binding domain / Ribosomal protein L11/L12 / Ribosomal protein L28/L24 superfamily / Ribosomal protein L9, N-terminal domain superfamily / Ribosomal protein L9 / Ribosomal protein L9, N-terminal / Ribosomal protein L9, N-terminal domain / Ribosomal protein L9/RNase H1, N-terminal / Ribosomal protein L36 / Ribosomal protein L36 superfamily / Ribosomal protein L36 / Ribosomal protein L35 / Ribosomal protein L35 superfamily / Ribosomal protein L35 / Ribosomal L28 family / Ribosomal protein L33 / Ribosomal protein L33 / Ribosomal protein L28/L24 Similarity search - Domain/homology
TIGECYCLINE / : / : / RNA / RNA (> 10) / RNA (> 100) / RNA (> 1000) / Large ribosomal subunit protein mL52 / Mitochondrial ribosomal protein L18, isoform CRA_b / Large ribosomal subunit protein uL22m ...TIGECYCLINE / : / : / RNA / RNA (> 10) / RNA (> 100) / RNA (> 1000) / Large ribosomal subunit protein mL52 / Mitochondrial ribosomal protein L18, isoform CRA_b / Large ribosomal subunit protein uL22m / Large ribosomal subunit protein bL33m / Large ribosomal subunit protein uL3m / Large ribosomal subunit protein bL19m / Large ribosomal subunit protein bL28m / Large ribosomal subunit protein mL49 / Large ribosomal subunit protein mL62 / Large ribosomal subunit protein uL23m / Large ribosomal subunit protein mL51 / Large ribosomal subunit protein uL2m / Large ribosomal subunit protein mL54 / Large ribosomal subunit protein uL14m / Large ribosomal subunit protein bL21m / Large ribosomal subunit protein mL55 / Large ribosomal subunit protein uL10m / Large ribosomal subunit protein mL41 / Large ribosomal subunit protein mL50 / Large ribosomal subunit protein mL43 / Large ribosomal subunit protein mL64 / Large ribosomal subunit protein uL30m / Large ribosomal subunit protein uL24m / Large ribosomal subunit protein mL38 / Large ribosomal subunit protein mL53 / Large ribosomal subunit protein mL48 / Large ribosomal subunit protein bL34m / Large ribosomal subunit protein mL63 / Large ribosomal subunit protein mL45 / Large ribosomal subunit protein bL32m / Large ribosomal subunit protein bL20m / Large ribosomal subunit protein uL13m / Large ribosomal subunit protein bL9m / Large ribosomal subunit protein uL4m / Large ribosomal subunit protein mL37 / Large ribosomal subunit protein mL46 / Large ribosomal subunit protein mL44 / Large ribosomal subunit protein uL29m / Large ribosomal subunit protein mL65 / Large ribosomal subunit protein mL40 / Large ribosomal subunit protein bL17m / Large ribosomal subunit protein mL66 / Large ribosomal subunit protein uL16m / Large ribosomal subunit protein mL39 / Large ribosomal subunit protein bL35m / Large ribosomal subunit protein uL15m / Large ribosomal subunit protein bL36m / Large ribosomal subunit protein bL27m / Large ribosomal subunit protein uL11m / Large ribosomal subunit protein mL42 Similarity search - Component
Biological species
Homo sapiens (human)
Method
ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å
Journal: Nat Commun / Year: 2024 Title: Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline. Authors: Xiang Li / Mengjiao Wang / Timo Denk / Robert Buschauer / Yi Li / Roland Beckmann / Jingdong Cheng / 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.
L1: 16s rRNA L2: Val tRNA LB: Large ribosomal subunit protein uL2m LC: Large ribosomal subunit protein uL3m LD: Large ribosomal subunit protein uL4m LI: Large ribosomal subunit protein bL9m LJ: Large ribosomal subunit protein uL10m LK: Large ribosomal subunit protein uL11m LM: Large ribosomal subunit protein uL13m LN: Large ribosomal subunit protein uL14m LO: Large ribosomal subunit protein uL15m LP: Large ribosomal subunit protein uL16m LQ: Large ribosomal subunit protein bL17m LR: Mitochondrial ribosomal protein L18, isoform CRA_b LS: Large ribosomal subunit protein bL19m LT: Large ribosomal subunit protein bL20m LU: Large ribosomal subunit protein bL21m LV: 39S ribosomal protein L22, mitochondrial LW: Large ribosomal subunit protein uL23m LX: Large ribosomal subunit protein uL24m La: Large ribosomal subunit protein bL27m Lb: Large ribosomal subunit protein bL28m Lu: Large ribosomal subunit protein uL29m Ld: Large ribosomal subunit protein uL30m Lf: Large ribosomal subunit protein bL32m Lg: Large ribosomal subunit protein bL33m Lh: Large ribosomal subunit protein bL34m Li: Large ribosomal subunit protein bL35m Lj: Large ribosomal subunit protein bL36m Lk: Large ribosomal subunit protein mL37 Ll: Large ribosomal subunit protein mL38 Lm: Large ribosomal subunit protein mL39 Ln: Large ribosomal subunit protein mL40 Lo: Large ribosomal subunit protein mL41 Lp: Large ribosomal subunit protein mL42 Lq: Large ribosomal subunit protein mL43 Lr: Large ribosomal subunit protein mL44 Ls: Large ribosomal subunit protein mL45 Lt: Large ribosomal subunit protein mL46 Lv: Large ribosomal subunit protein mL48 Lw: Large ribosomal subunit protein mL49 Lx: Large ribosomal subunit protein mL50 Ly: Large ribosomal subunit protein mL51 Lz: 39S ribosomal protein L52, mitochondrial L3: Large ribosomal subunit protein mL53 L4: Large ribosomal subunit protein mL54 L5: Large ribosomal subunit protein mL55 L6: Large ribosomal subunit protein mL63 L7: Large ribosomal subunit protein mL62 L8: Large ribosomal subunit protein mL64 SR: Large ribosomal subunit protein mL66 Sf: Large ribosomal subunit protein mL65 hetero molecules
Mass: 23674.203 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q14197, peptidyl-tRNA hydrolase
#50: Protein
LargeribosomalsubunitproteinmL64 / 39S ribosomal protein L59 / mitochondrial / MRP-L59 / CKII beta-associating protein / CR6- ...39S ribosomal protein L59 / mitochondrial / MRP-L59 / CKII beta-associating protein / CR6-interacting factor 1 / CRIF1 / Growth arrest and DNA damage-inducible proteins-interacting protein 1 / Papillomavirus L2-interacting nuclear protein 1 / PLINP / PLINP-1 / p53-responsive gene 6 protein
Mass: 25426.895 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q8TAE8
#51: Protein
LargeribosomalsubunitproteinmL66 / 39S ribosomal protein S18-3 / mitochondrial / MRP-S18-3 / 39S ribosomal protein S18a / MRP-S18-a / ...39S ribosomal protein S18-3 / mitochondrial / MRP-S18-3 / 39S ribosomal protein S18a / MRP-S18-a / Mrps18a / S18mt-a / Large ribosomal subunit protein bS18a
Mass: 22224.078 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9NVS2
#52: Protein
LargeribosomalsubunitproteinmL65 / 39S ribosomal protein S30 / mitochondrial / MRP-S30 / S30mt / Large ribosomal subunit protein mS30 ...39S ribosomal protein S30 / mitochondrial / MRP-S30 / S30mt / Large ribosomal subunit protein mS30 / Programmed cell death protein 9
Mass: 50429.578 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9NP92
-
Protein , 1 types, 1 molecules LR
#14: Protein
MitochondrialribosomalproteinL18, isoformCRA_b / cDNA FLJ76688 / highly similar to Homo sapiens HSPC071 mRNA
Mass: 20465.348 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: A8K9D2
-
39S ribosomal protein ... , 2 types, 2 molecules LVLz
#18: Protein
39SribosomalproteinL22, mitochondrial
Mass: 24369.527 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: E7ESL0
#44: Protein
39SribosomalproteinL52, mitochondrial
Mass: 13696.684 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: A8K7J6
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