[English] 日本語
Yorodumi- PDB-6az3: Cryo-EM structure of of the large subunit of Leishmania ribosome ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6az3 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of of the large subunit of Leishmania ribosome bound to paromomycin | |||||||||
Components |
| |||||||||
Keywords | RIBOSOME/ANTIBIOTIC / Leishmania / ribosome / aminoglycoside / paromomycin / RIBOSOME-ANTIBIOTIC complex | |||||||||
Function / homology | Function and homology information protein-RNA complex assembly / maturation of LSU-rRNA / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / large ribosomal subunit / ribosome biogenesis / 5S rRNA binding / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / cytoplasmic translation ...protein-RNA complex assembly / maturation of LSU-rRNA / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / large ribosomal subunit / ribosome biogenesis / 5S rRNA binding / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / cytoplasmic translation / rRNA binding / ribosome / structural constituent of ribosome / translation / ribonucleoprotein complex / mRNA binding / RNA binding / membrane / nucleus / metal ion binding / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Leishmania donovani (eukaryote) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.5 Å | |||||||||
Authors | Shalev-Benami, M. / Zhang, Y. / Rozenberg, H. / Nobe, Y. / Taoka, M. / Matzov, D. / Zimmerman, E. / Bashan, A. / Isobe, T. / Jaffe, C.L. ...Shalev-Benami, M. / Zhang, Y. / Rozenberg, H. / Nobe, Y. / Taoka, M. / Matzov, D. / Zimmerman, E. / Bashan, A. / Isobe, T. / Jaffe, C.L. / Yonath, A. / Skiniotis, G. | |||||||||
Citation | Journal: Nat Commun / Year: 2017 Title: Atomic resolution snapshot of Leishmania ribosome inhibition by the aminoglycoside paromomycin. Authors: Moran Shalev-Benami / Yan Zhang / Haim Rozenberg / Yuko Nobe / Masato Taoka / Donna Matzov / Ella Zimmerman / Anat Bashan / Toshiaki Isobe / Charles L Jaffe / Ada Yonath / Georgios Skiniotis / Abstract: Leishmania is a single-celled eukaryotic parasite afflicting millions of humans worldwide, with current therapies limited to a poor selection of drugs that mostly target elements in the parasite's ...Leishmania is a single-celled eukaryotic parasite afflicting millions of humans worldwide, with current therapies limited to a poor selection of drugs that mostly target elements in the parasite's cell envelope. Here we determined the atomic resolution electron cryo-microscopy (cryo-EM) structure of the Leishmania ribosome in complex with paromomycin (PAR), a highly potent compound recently approved for treatment of the fatal visceral leishmaniasis (VL). The structure reveals the mechanism by which the drug induces its deleterious effects on the parasite. We further show that PAR interferes with several aspects of cytosolic translation, thus highlighting the cytosolic rather than the mitochondrial ribosome as the primary drug target. The results also highlight unique as well as conserved elements in the PAR-binding pocket that can serve as hotspots for the development of novel therapeutics. | |||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6az3.cif.gz | 2.8 MB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6az3.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 6az3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6az3_validation.pdf.gz | 1.8 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 6az3_full_validation.pdf.gz | 2 MB | Display | |
Data in XML | 6az3_validation.xml.gz | 213.6 KB | Display | |
Data in CIF | 6az3_validation.cif.gz | 363.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/az/6az3 ftp://data.pdbj.org/pub/pdb/validation_reports/az/6az3 | HTTPS FTP |
-Related structure data
Related structure data | 7025MC 7024C 6az1C M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Ribosomal protein ... , 12 types, 12 molecules ABCFHIMQWXgn
#1: Protein | Mass: 27520.994 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) |
---|---|
#2: Protein | Mass: 45741.395 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) |
#3: Protein | Mass: 40523.211 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: UniProt: A0A3S5H7L0, UniProt: E9BKR3*PLUS |
#6: Protein | Mass: 21208.869 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) |
#8: Protein | Mass: 25346.008 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) |
#9: Protein | Mass: 23897.861 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) |
#13: Protein | Mass: 24366.773 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: UniProt: A0A3Q8IIZ6, UniProt: E9BMB4*PLUS |
#17: Protein | Mass: 22901.018 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: UniProt: A0A504XXD2, UniProt: E9B8Q2*PLUS |
#23: Protein | Mass: 13874.408 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) |
#24: Protein | Mass: 7988.512 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) |
#33: Protein | Mass: 14336.777 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: UniProt: A0A3Q8II82, UniProt: E9BR22*PLUS |
#40: Protein/peptide | Mass: 4259.300 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) |
+60S ribosomal protein ... , 23 types, 23 molecules DEGJLNOPRSTUVZbcdhijlop
-Protein , 6 types, 6 molecules KYaefk
#11: Protein | Mass: 17038.955 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: UniProt: Q25278 |
---|---|
#25: Protein | Mass: 15223.005 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: UniProt: A0A504XEJ0, UniProt: E9BP34*PLUS |
#27: Protein | Mass: 14987.824 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: UniProt: A0A504XWA8, UniProt: E9BIP6*PLUS |
#31: Protein | Mass: 13503.024 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: UniProt: A0A3Q8IJL7, UniProt: E9BSK4*PLUS |
#32: Protein | Mass: 15029.650 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: UniProt: A0A504XZK6, UniProt: E9BFJ5*PLUS |
#37: Protein | Mass: 8761.474 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: UniProt: A0A504WZU0, UniProt: E9B7P2*PLUS |
-Protein/peptide , 1 types, 1 molecules m
#39: Protein/peptide | Mass: 5912.278 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: UniProt: A0A3Q8ISR1, UniProt: E9BMW6*PLUS |
---|
-RNA chain , 8 types, 8 molecules 12345678
#43: RNA chain | Mass: 575707.562 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: GenBank: 322500086 |
---|---|
#44: RNA chain | Mass: 492460.781 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: GenBank: 322500086 |
#45: RNA chain | Mass: 67568.750 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: GenBank: 322500086 |
#46: RNA chain | Mass: 59144.129 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: GenBank: 5019758 |
#47: RNA chain | Mass: 42869.438 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: GenBank: 5019758 |
#48: RNA chain | Mass: 22725.590 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: GenBank: 5019758 |
#49: RNA chain | Mass: 54989.570 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: GenBank: 1229082208 |
#50: RNA chain | Mass: 37923.516 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Leishmania donovani (eukaryote) / References: GenBank: 1229082190 |
-Non-polymers , 3 types, 1063 molecules
#51: Chemical | ChemComp-PAR / #52: Chemical | ChemComp-MG / #53: Water | ChemComp-HOH / | |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Leishmania donovani 91S ribosome LSU / Type: RIBOSOME / Entity ID: #1-#50 / Source: NATURAL |
---|---|
Molecular weight | Units: MEGADALTONS / Experimental value: NO |
Source (natural) | Organism: Leishmania donovani (eukaryote) |
Buffer solution | pH: 7.6 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 1 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
---|---|
3D reconstruction | Resolution: 2.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 141028 / Symmetry type: POINT |