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My question concerns the mode of action of 30s ribosomal antibiotc inhibitors — tetracyclines. According to some online resources, the antibiotics enter the A-site, which prevents other tRNA from entering the ribosome. Others say that the antibiotic prevents the ribosome from moving along the mRNA. Which one is correct?

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    $\begingroup$ Adding references and citations to the "resources" and also naming the particular drug you were interested in would help your chances of getting this question answered considerably. $\endgroup$ – AMR Jan 19 '16 at 16:51
  • $\begingroup$ I am giving the class of antibiotics. 30s ribosomal Inhibitors. Some examples: Aminoglycosides Tetracyclines. $\endgroup$ – A. Radek Martinez Jan 19 '16 at 17:12
  • $\begingroup$ Firstly, as AMR said, you should add the online resources which you referred to. Secondly, different antibiotics can have different effects. In fact there can be different effects based on concentration. Moreover, it is now established that aminoglycosides are bactericidal because they not just prevent translation but also cause mistranslation leading to toxic products. $\endgroup$ – WYSIWYG Jan 19 '16 at 17:17
  • $\begingroup$ Could you expand on "how they prevent" translation. $\endgroup$ – A. Radek Martinez Jan 19 '16 at 17:19
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    $\begingroup$ @RadekMartinez can you first please add references and focus your question on one class of antibiotics such as aminogycosides. $\endgroup$ – WYSIWYG Jan 20 '16 at 5:48
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The crystal structure of tetracycline bound to the 30S ribosomal subunit of Thermus thermophilus has been determined by Pioletti et al. and the major binding site (Tet-1) interferes with the location where the A-site tRNA binds as shown in the stereo pair, below:

Tet-1 binding site

They write:

“Thus tetracycline can physically prevent the binding of the tRNA to the A-site. This mode of interaction is consistent with the classical model of tetracycline as an inhibitor of A-site occupation, and hence offers a clear explanation of the bacteriostatic effects of tetracycline.”

So the proximal effect would appear to be the first alternative in the question, although the second may be an indirect consequence.

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