scholarly journals Antibiotics targeting bacterial ribosomal subunit biogenesis

2020 ◽  
Vol 75 (4) ◽  
pp. 787-806
Author(s):  
W Scott Champney

Abstract This article describes 20 years of research that investigated a second novel target for ribosomal antibiotics, the biogenesis of the two subunits. Over that period, we have examined the effect of 52 different antibiotics on ribosomal subunit formation in six different microorganisms. Most of the antimicrobials we have studied are specific, preventing the formation of only the subunit to which they bind. A few interesting exceptions have also been observed. Forty-one research publications and a book chapter have resulted from this investigation. This review will describe the methodology we used and the fit of our results to a hypothetical model. The model predicts that inhibition of subunit assembly and translation are equivalent targets for most of the antibiotics we have investigated.

Nature ◽  
1988 ◽  
Vol 336 (6198) ◽  
pp. 496-498 ◽  
Author(s):  
Kayoko Nishi ◽  
Francoise Morel-Deville ◽  
John W. B. Hershey ◽  
Terrance Leighton ◽  
Joachim Schnier

2007 ◽  
Vol 28 (3) ◽  
pp. 434-445 ◽  
Author(s):  
Partha P. Datta ◽  
Daniel N. Wilson ◽  
Masahito Kawazoe ◽  
Neil K. Swami ◽  
Tatsuya Kaminishi ◽  
...  

2006 ◽  
Vol 281 (12) ◽  
pp. 8110-8117 ◽  
Author(s):  
Yoshitaka Matsuo ◽  
Takuya Morimoto ◽  
Masayoshi Kuwano ◽  
Pek Chin Loh ◽  
Taku Oshima ◽  
...  

2019 ◽  
Vol 47 (19) ◽  
pp. 10414-10425 ◽  
Author(s):  
Amal Seffouh ◽  
Nikhil Jain ◽  
Dushyant Jahagirdar ◽  
Kaustuv Basu ◽  
Aida Razi ◽  
...  

Abstract Bacteria harbor a number GTPases that function in the assembly of the ribosome and are essential for growth. RbgA is one of these GTPases and is required for the assembly of the 50S subunit in most bacteria. Homologs of this protein are also implicated in the assembly of the large subunit of the mitochondrial and eukaryotic ribosome. We present here the cryo-electron microscopy structure of RbgA bound to a Bacillus subtilis 50S subunit assembly intermediate (45SRbgA particle) that accumulates in cells upon RbgA depletion. Binding of RbgA at the P site of the immature particle stabilizes functionally important rRNA helices in the A and P-sites, prior to the completion of the maturation process of the subunit. The structure also reveals the location of the highly conserved N-terminal end of RbgA containing the catalytic residue Histidine 9. The derived model supports a mechanism of GTP hydrolysis, and it shows that upon interaction of RbgA with the 45SRbgA particle, Histidine 9 positions itself near the nucleotide potentially acting as the catalytic residue with minimal rearrangements. This structure represents the first visualization of the conformational changes induced by an assembly factor in a bacterial subunit intermediate.


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