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TitleStructural insights into species-specific features of the ribosome from the pathogen Staphylococcus aureus.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 112, Issue 43, Page E5805-E5814, Year 2015
Publish dateOct 27, 2015
AuthorsZohar Eyal / Donna Matzov / Miri Krupkin / Itai Wekselman / Susanne Paukner / Ella Zimmerman / Haim Rozenberg / Anat Bashan / Ada Yonath /
PubMed AbstractThe emergence of bacterial multidrug resistance to antibiotics threatens to cause regression to the preantibiotic era. Here we present the crystal structure of the large ribosomal subunit from ...The emergence of bacterial multidrug resistance to antibiotics threatens to cause regression to the preantibiotic era. Here we present the crystal structure of the large ribosomal subunit from Staphylococcus aureus, a versatile Gram-positive aggressive pathogen, and its complexes with the known antibiotics linezolid and telithromycin, as well as with a new, highly potent pleuromutilin derivative, BC-3205. These crystal structures shed light on specific structural motifs of the S. aureus ribosome and the binding modes of the aforementioned antibiotics. Moreover, by analyzing the ribosome structure and comparing it with those of nonpathogenic bacterial models, we identified some unique internal and peripheral structural motifs that may be potential candidates for improving known antibiotics and for use in the design of selective antibiotic drugs against S. aureus.
External linksProc Natl Acad Sci U S A / PubMed:26464510 / PubMed Central
MethodsX-ray diffraction
Resolution3.392 - 3.526 Å
Structure data

PDB-4wce:
The crystal structure of the large ribosomal subunit of Staphylococcus aureus
Method: X-RAY DIFFRACTION / Resolution: 3.526 Å

PDB-4wf9:
The crystal structure of the large ribosomal subunit of Staphylococcus aureus in complex with telithromycin
Method: X-RAY DIFFRACTION / Resolution: 3.427 Å

PDB-4wfa:
The crystal structure of the large ribosomal subunit of Staphylococcus aureus in complex with linezolid
Method: X-RAY DIFFRACTION / Resolution: 3.392 Å

PDB-4wfb:
The crystal structure of the large ribosomal subunit of Staphylococcus aureus in complex with BC-3205
Method: X-RAY DIFFRACTION / Resolution: 3.43 Å

Chemicals

ChemComp-MPD:
(4S)-2-METHYL-2,4-PENTANEDIOL / precipitant*YM / 2-Methyl-2,4-pentanediol

ChemComp-MN:
Unknown entry

ChemComp-MG:
Unknown entry

ChemComp-EPE:
4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID / pH buffer*YM / HEPES

ChemComp-SPD:
SPERMIDINE / Spermidine

ChemComp-EOH:
ETHANOL / Ethanol

ChemComp-TEL:
TELITHROMYCIN / antibiotic*YM / Telithromycin

ChemComp-ZLD:
N-{[(5S)-3-(3-fluoro-4-morpholin-4-ylphenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide / antibiotic*YM / Linezolid

ChemComp-NA:
Unknown entry

ChemComp-3LK:
BC-3205

Source
  • staphylococcus aureus (bacteria)
  • staphylococcus aureus subsp. aureus nctc 8325 (bacteria)
  • staphylococcus aureus (strain nctc 8325) (bacteria)
  • staphylococcus aureus (strain usa300) (bacteria)
KeywordsRIBOSOME / RNA / bacteria

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