[English] 日本語
Yorodumi
- PDB-7ttw: 50S ribosomal subunit from Staphylococcus aureus containing doubl... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7ttw
Title50S ribosomal subunit from Staphylococcus aureus containing double mutation in uL3 imparting linezolid resistance
Components
  • (50S ribosomal protein ...) x 25
  • 23S rRNA23S ribosomal RNA
  • 5S rRNA5S ribosomal RNA
KeywordsRIBOSOME / 50S subunit / antibiotic resistance / linezolid
Function / homology
Function and homology information


large ribosomal subunit / 5S rRNA binding / transferase activity / tRNA binding / rRNA binding / ribosome / structural constituent of ribosome / ribonucleoprotein complex / translation / cytoplasm
Similarity search - Function
Ribosomal protein L25, long-form / Ribosomal protein L25, beta domain / Ribosomal protein L25, C-terminal / Ribosomal protein TL5, C-terminal domain / Ribosomal protein L16 signature 1. / : / Ribosomal protein L16, conserved site / Ribosomal protein L16 signature 2. / Ribosomal protein L17 signature. / Ribosomal L25p family ...Ribosomal protein L25, long-form / Ribosomal protein L25, beta domain / Ribosomal protein L25, C-terminal / Ribosomal protein TL5, C-terminal domain / Ribosomal protein L16 signature 1. / : / Ribosomal protein L16, conserved site / Ribosomal protein L16 signature 2. / Ribosomal protein L17 signature. / Ribosomal L25p family / Ribosomal protein L25 / Ribosomal protein L28/L24 superfamily / Ribosomal protein L36 signature. / Ribosomal protein L25/Gln-tRNA synthetase, N-terminal / Ribosomal protein L32p, bacterial type / Ribosomal protein L25/Gln-tRNA synthetase, anti-codon-binding domain superfamily / Ribosomal protein L28 / Ribosomal protein L35, conserved site / Ribosomal protein L35 signature. / Ribosomal protein L33, conserved site / Ribosomal protein L33 signature. / Ribosomal protein L35, non-mitochondrial / Ribosomal protein L18, bacterial-type / Ribosomal protein L19, conserved site / Ribosomal protein L19 signature. / Ribosomal protein L36 / Ribosomal protein L36 superfamily / Ribosomal protein L36 / Ribosomal protein L20 signature. / Ribosomal protein L27, conserved site / Ribosomal protein L27 signature. / Ribosomal protein L14P, bacterial-type / Ribosomal protein L34, conserved site / Ribosomal protein L34 signature. / Ribosomal protein L22, bacterial/chloroplast-type / Ribosomal protein L35 / Ribosomal protein L35 superfamily / Ribosomal protein L2, bacterial/organellar-type / Ribosomal protein L35 / Ribosomal L28 family / Ribosomal protein L33 / Ribosomal protein L33 / Ribosomal protein L28/L24 / Ribosomal protein L33 superfamily / Ribosomal protein L30, bacterial-type / Ribosomal protein L16 / Ribosomal protein L18 / Ribosomal L18 of archaea, bacteria, mitoch. and chloroplast / L28p-like / Ribosomal protein L20 / Ribosomal protein L20 / Ribosomal protein L20, C-terminal / Ribosomal protein L21 / Ribosomal protein L27 / Ribosomal L27 protein / Ribosomal protein L19 / Ribosomal protein L19 superfamily / Ribosomal protein L19 / Ribosomal proteins 50S L24/mitochondrial 39S L24 / Ribosomal protein L17 / Ribosomal protein L17 superfamily / Ribosomal protein L17 / Ribosomal protein L21-like / L21-like superfamily / Ribosomal prokaryotic L21 protein / Ribosomal L32p protein family / Ribosomal protein L24 / Ribosomal protein L32p / Ribosomal protein L34 / Ribosomal protein L34 / Ribosomal protein L13, bacterial-type / Ribosomal protein L3, bacterial/organelle-type / Ribosomal protein L15, bacterial-type / 50S ribosomal protein uL4 / : / Ribosomal protein L15, conserved site / Ribosomal protein L2, conserved site / Ribosomal protein L2 signature. / Ribosomal protein L10e/L16 / Ribosomal protein L10e/L16 superfamily / Ribosomal protein L16p/L10e / Ribosomal protein L2, domain 3 / Ribosomal protein L14P, conserved site / Ribosomal protein L15 signature. / Ribosomal protein L22/L17, conserved site / Ribosomal protein L29/L35 / Ribosomal protein L29/L35 superfamily / Ribosomal L29 protein / Ribosomal protein L13, conserved site / Ribosomal protein L13 signature. / Ribosomal protein L24/L26, conserved site / KOW (Kyprides, Ouzounis, Woese) motif. / Ribosomal Proteins L2, C-terminal domain / Ribosomal protein L2, C-terminal / Ribosomal Proteins L2, C-terminal domain / Ribosomal Proteins L2, RNA binding domain / Ribosomal Proteins L2, RNA binding domain / Ribosomal protein L2 / Ribosomal protein L14 signature. / Ribosomal protein L22 signature.
Similarity search - Domain/homology
: / RNA / RNA (> 10) / RNA (> 100) / RNA (> 1000) / Large ribosomal subunit protein bL17 / Large ribosomal subunit protein uL15 / Large ribosomal subunit protein bL36 / Large ribosomal subunit protein bL28 / Large ribosomal subunit protein uL14 ...: / RNA / RNA (> 10) / RNA (> 100) / RNA (> 1000) / Large ribosomal subunit protein bL17 / Large ribosomal subunit protein uL15 / Large ribosomal subunit protein bL36 / Large ribosomal subunit protein bL28 / Large ribosomal subunit protein uL14 / Large ribosomal subunit protein bL19 / Large ribosomal subunit protein bL32 / Large ribosomal subunit protein bL33 / Large ribosomal subunit protein uL16 / Large ribosomal subunit protein bL20 / Large ribosomal subunit protein uL2 / 50S ribosomal protein L3 / 50S ribosomal protein L35 / 50S ribosomal protein L27 / 50S ribosomal protein L22 / Large ribosomal subunit protein bL25 / 50S ribosomal protein L4 / 50S ribosomal protein L29 / Large ribosomal subunit protein bL21 / Large ribosomal subunit protein bL34 / Large ribosomal subunit protein uL24 / Large ribosomal subunit protein uL18 / Large ribosomal subunit protein uL23 / Large ribosomal subunit protein uL13 / Large ribosomal subunit protein uL30
Similarity search - Component
Biological speciesStaphylococcus aureus (bacteria)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å
AuthorsBelousoff, M.J. / Piper, S. / Johnson, R.
Funding support United States, Australia, 3items
OrganizationGrant numberCountry
Department of Defense (DOD, United States)W81XWH1910126 United States
National Health and Medical Research Council (NHMRC, Australia)1092262 Australia
Australian Research Council (ARC)170103567 Australia
CitationJournal: Microbiol Spectr / Year: 2022
Title: A Structurally Characterized Evolutionary Escape Route from Treatment with the Antibiotic Linezolid.
Authors: Laura Perlaza-Jiménez / Kher-Shing Tan / Sarah J Piper / Rachel M Johnson / Rebecca S Bamert / Christopher J Stubenrauch / Alexander Wright / David Lupton / Trevor Lithgow / Matthew J Belousoff /
Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterial pathogen that presents great health concerns. Treatment requires the use of last-line antibiotics, such as members of the ...Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterial pathogen that presents great health concerns. Treatment requires the use of last-line antibiotics, such as members of the oxazolidinone family, of which linezolid is the first member to see regular use in the clinic. Here, we report a short time scale selection experiment in which strains of MRSA were subjected to linezolid treatment. Clonal isolates which had evolved a linezolid-resistant phenotype were characterized by whole-genome sequencing. Linezolid-resistant mutants were identified which had accumulated mutations in the ribosomal protein uL3. Multiple clones which had two mutations in uL3 exhibited resistance to linezolid, 2-fold higher than the clinical breakpoint. Ribosomes from this strain were isolated and subjected to single-particle cryo-electron microscopic analysis and compared to the ribosomes from the parent strain. We found that the mutations in uL3 lead to a rearrangement of a loop that makes contact with Helix 90, propagating a structural change over 15 Å away. This distal change swings nucleotide U2504 into the binding site of the antibiotic, causing linezolid resistance. Antibiotic resistance poses a critical problem to human health and decreases the utility of these lifesaving drugs. Of particular concern is the "superbug" methicillin-resistant Staphylococcus aureus (MRSA), for which treatment of infection requires the use of last-line antibiotics, including linezolid. In this paper, we characterize the atomic rearrangements which the ribosome, the target of linezolid, undergoes during its evolutionary journey toward becoming drug resistant. Using cryo-electron microscopy, we describe a particular molecular mechanism which MRSA uses to become resistant to linezolid.
History
DepositionFeb 2, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 6, 2022Provider: repository / Type: Initial release
Revision 1.1Sep 14, 2022Group: Database references / Category: citation / Item: _citation.journal_volume

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 50S ribosomal protein L19
B: 50S ribosomal protein L2
C: 50S ribosomal protein L20
D: 50S ribosomal protein L21
E: 50S ribosomal protein L22
F: 50S ribosomal protein L23
G: 50S ribosomal protein L24
H: 50S ribosomal protein L25
I: 50S ribosomal protein L27
J: 50S ribosomal protein L28
K: 50S ribosomal protein L29
L: 50S ribosomal protein L3
M: 50S ribosomal protein L30
N: 50S ribosomal protein L32
O: 50S ribosomal protein L33
P: 50S ribosomal protein L34
Q: 50S ribosomal protein L35
R: 50S ribosomal protein L36
S: 50S ribosomal protein L4
V: 50S ribosomal protein L13
W: 50S ribosomal protein L14
X: 50S ribosomal protein L15
Y: 50S ribosomal protein L16
Z: 50S ribosomal protein L17
a: 50S ribosomal protein L18
1: 23S rRNA
2: 5S rRNA


Theoretical massNumber of molelcules
Total (without water)1,307,60027
Polymers1,307,60027
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

+
50S ribosomal protein ... , 25 types, 25 molecules ABCDEFGHIJKLMNOPQRSVWXYZa

#1: Protein 50S ribosomal protein L19 /


Mass: 13392.771 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: A0A077UVB6
#2: Protein 50S ribosomal protein L2 /


Mass: 30217.164 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: A0A077W1J0
#3: Protein 50S ribosomal protein L20 /


Mass: 13720.295 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: A0A077VMP6
#4: Protein 50S ribosomal protein L21 /


Mass: 11354.081 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: D7URR3
#5: Protein 50S ribosomal protein L22 /


Mass: 12857.922 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: A0A0D1H5C2
#6: Protein 50S ribosomal protein L23 /


Mass: 10181.837 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: W8TUB4
#7: Protein 50S ribosomal protein L24 /


Mass: 11561.504 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: W8TRD5
#8: Protein 50S ribosomal protein L25 / / General stress protein CTC


Mass: 23810.609 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: A0A133Q8Z9
#9: Protein 50S ribosomal protein L27 /


Mass: 10334.798 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: A0A0D1H0B5
#10: Protein 50S ribosomal protein L28 /


Mass: 6896.158 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: A0A077URJ8
#11: Protein 50S ribosomal protein L29 /


Mass: 8592.900 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: A0A7R6P2U0
#12: Protein 50S ribosomal protein L3 /


Mass: 23842.361 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: A0A0D1GR95
#13: Protein 50S ribosomal protein L30 /


Mass: 6565.683 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: W8UVN7
#14: Protein 50S ribosomal protein L32 /


Mass: 6500.609 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: A0A077UWR7
#15: Protein/peptide 50S ribosomal protein L33 /


Mass: 5885.783 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: A0A077UXT4
#16: Protein/peptide 50S ribosomal protein L34 /


Mass: 5454.642 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: Q2YZB6
#17: Protein 50S ribosomal protein L35 /


Mass: 7593.188 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: A0A0D1H088
#18: Protein/peptide 50S ribosomal protein L36 /


Mass: 4318.422 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: A0A077UGV8
#19: Protein 50S ribosomal protein L4 /


Mass: 22523.752 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: A0A166DK89
#20: Protein 50S ribosomal protein L13 /


Mass: 16359.427 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: W8TUE6
#21: Protein 50S ribosomal protein L14 /


Mass: 13157.342 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: A0A077UUA0
#22: Protein 50S ribosomal protein L15 /


Mass: 15628.890 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: A0A077UGA7
#23: Protein 50S ribosomal protein L16 /


Mass: 16274.049 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: A0A077V4G0
#24: Protein 50S ribosomal protein L17 /


Mass: 13771.773 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: A0A077UG91
#25: Protein 50S ribosomal protein L18 /


Mass: 13124.093 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: UniProt: W8TRE0

-
RNA chain , 2 types, 2 molecules 12

#26: RNA chain 23S rRNA / 23S ribosomal RNA


Mass: 946680.625 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria) / References: GenBank: 1877770729
#27: RNA chain 5S rRNA / 5S ribosomal RNA


Mass: 36998.973 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Staphylococcus aureus (bacteria)

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: 50S ribosomal subunit from Staphylococcus aureus - double mutation in uL3 leading to linezolid resistance
Type: RIBOSOME / Entity ID: all / Source: NATURAL
Molecular weightExperimental value: NO
Source (natural)Organism: Staphylococcus aureus (bacteria)
Buffer solutionpH: 7.4
SpecimenConc.: 0.3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

MicroscopyModel: TFS GLACIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1500 nm / Nominal defocus min: 500 nm / C2 aperture diameter: 50 µm
Image recordingElectron dose: 47.5 e/Å2 / Detector mode: COUNTING / Film or detector model: FEI FALCON III (4k x 4k)

-
Processing

SoftwareName: PHENIX / Version: 1.19.2_4158: / Classification: refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 307600 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00288327
ELECTRON MICROSCOPYf_angle_d0.525133048
ELECTRON MICROSCOPYf_dihedral_angle_d14.54936506
ELECTRON MICROSCOPYf_chiral_restr0.03317153
ELECTRON MICROSCOPYf_plane_restr0.0046418

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more