scholarly journals Structural insights into species-specific features of the ribosome from the pathogen Staphylococcus aureus

2015 ◽  
Vol 112 (43) ◽  
pp. E5805-E5814 ◽  
Author(s):  
Zohar Eyal ◽  
Donna Matzov ◽  
Miri Krupkin ◽  
Itai Wekselman ◽  
Susanne Paukner ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Staphylococcus Aureus ◽  
Ribosomal Subunit ◽  
Binding Modes ◽  
Large Ribosomal Subunit ◽  
Structural Motifs ◽  
Antibiotic Drugs ◽  
Species Specific ◽  
Structural Insights ◽  
Shed Light

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.

scholarly journals Structural Insight into the Antibiotic Action of Telithromycin against Resistant Mutants

2003 ◽  
Vol 185 (14) ◽  
pp. 4276-4279 ◽  
Author(s):  
Rita Berisio ◽  
Joerg Harms ◽  
Frank Schluenzen ◽  
Raz Zarivach ◽  
Harly A. S. Hansen ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Deinococcus Radiodurans ◽  
Ribosomal Subunit ◽  
Large Ribosomal Subunit ◽  
Resistant Strains ◽  
Structural Insight ◽  
Resistant Mutants ◽  
Exit Tunnel ◽  
Structural Insights ◽  
Insight Into

ABSTRACT The crystal structure of the ketolide telithromycin bound to the Deinococcus radiodurans large ribosomal subunit shows that telithromycin blocks the ribosomal exit tunnel and interacts with domains II and V of the 23S RNA. Comparisons to other clinically relevant macrolides provided structural insights into its enhanced activity against macrolide-resistant strains.

Crystal Structure of the Large Ribosomal Subunit at 5-Angstrom Resolution

The Ribosome ◽  
2014 ◽  
pp. 11-20
Author(s):  
Nenad Ban ◽  
Poul Nissen ◽  
Peter B. Moore ◽  
Thomas A. Steitz
Keyword(s):  
Crystal Structure ◽  
Ribosomal Subunit ◽  
Large Ribosomal Subunit

scholarly journals Crystal structure of the synergistic antibiotic pair, lankamycin and lankacidin, in complex with the large ribosomal subunit

2011 ◽  
Vol 108 (7) ◽  
pp. 2717-2722 ◽  
Author(s):  
M. J. Belousoff ◽  
T. Shapira ◽  
A. Bashan ◽  
E. Zimmerman ◽  
H. Rozenberg ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Ribosomal Subunit ◽  
Large Ribosomal Subunit

scholarly journals Crystal structure of human endothelin ETb receptor in complex with peptide inverse agonist IRL2500

2018 ◽  
Author(s):  
Chisae Nagiri ◽  
Wataru Shihoya ◽  
Asuka Inoue ◽  
Francois Marie Ngako Kadji ◽  
Junken Aoki ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Chemical Space ◽  
Inverse Agonist ◽  
Binding Modes ◽  
Endothelin 1 ◽  
Class A ◽  
Etb Receptor ◽  
G Protein Coupled ◽  
Structural Insights ◽  
Preventive Effects

AbstractEndothelin receptors (ET A and ET B) are G-protein coupled receptors activated by endothelin-1 and are involved in blood pressure regulation. IRL2500 is a peptide-mimetic of the C-terminal tripeptide of endothelin-1, and has been characterized as a potent ET B-selective antagonist, which has preventive effects against brain edema. Here, we report the crystal structure of the human ET B receptor in complex with IRL2500 at 2.7 A-resolution. The structure revealed the different binding modes between IRL2500 and ET-1, and provides structural insights into its ET B-selectivity. Notably, the biphenyl group of IRL2500 penetrates into the transmembrane core proximal to D2.50, stabilizing the inactive conformation. Using the newly-established constitutively active mutant, we clearly demonstrate that IRL2500 functions as an inverse agonist for the ET B receptor. The current findings will expand the chemical space of ETR antagonists and facilitate the design of inverse agonists for other class A GPCRs.

scholarly journals Transcriptional and Translational Control of the mlr Operon, Which Confers Resistance to Seven Classes of Protein Synthesis Inhibitors

2008 ◽  
Vol 52 (5) ◽  
pp. 1703-1712 ◽  
Author(s):  
Lisa K. Smith ◽  
Alexander S. Mankin
Keyword(s):  
Staphylococcus Aureus ◽  
Translational Control ◽  
Ribosomal Subunit ◽  
Open Reading Frames ◽  
23S Rrna ◽  
Large Ribosomal Subunit ◽  
Protein Synthesis Inhibitors ◽  
Translation Control ◽  
Combined Action ◽  
Reading Frames

ABSTRACT The methyltransferase genes erm(B) and cfr are adjacent to each other in the chromosome of methicillin-resistant Staphylococcus aureus strain CM05. Analyses of the transcriptional organization of the erm(B) and cfr genes in the chromosome of strain CM05 showed that the two genes are organized into an operon, designated mlr (for modification of the large ribosomal subunit), which is controlled by the erm(B) promoter. Analysis of the translation control and the inducibility of the erm(B) and cfr genes in the mlr operon showed that despite the presence of putative regulatory short open reading frames, both genes are expressed constitutively. The combined action of the two methyltransferases encoded in the mlr operon results in modification of two specific residues in 23S rRNA, A2058 and A2503, and renders cells resistant to all clinically useful antibiotics that target the large ribosomal subunit. Furthermore, simultaneous modification of both rRNA sites synergistically enhances resistance to 16-member-ring macrolides.

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