peptidyltransferase VS transpeptidation

[stronghold]

What is the difference between peptidyltransferase and transpeptidation? Chloramphenicol blocks the former, while clindamycin blocks the latter. However, I don't know the difference between them? Where in translation process are they?

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[VCorp]

Peptidyltransferase is responsible for moving the amino acids from the P-site to the A-site, it's a part of translocation. As you correctly mentioned, it's inhibited by chloramphenicol.

Transpeptidation is a process used by bacteria for cell wall synthesis. The beta-lactam drugs (ie penicillin, cephalosporin, imipenem, etc) all block the process of transpeptidation. It has nothing to do with translocation.

 

[stronghold]

Peptidyltransferase is responsible for moving the amino acids from the P-site to the A-site, it's a part of translocation. As you correctly mentioned, it's inhibited by chloramphenicol.

Transpeptidation is a process used by bacteria for cell wall synthesis. The beta-lactam drugs (ie penicillin, cephalosporin, imipenem, etc) all block the process of transpeptidation. It has nothing to do with translocation.

Thanks for your input. Although transpeptidation is used in cell wall synthesis, there is another transpeptidation used during protein synthesis (translation) which is inhibited by clindamycin.

I hope somebody can help to understand where that transpeptidation, inhibited by clindamycin, exactly occurs during translation.

 

[Rac65]

Transpeptidase (a protein enzyme) links two peptidoglycan subunits (chains) as part of the wall synthesis process.
Peptidyl transferase (a ribozyme) links two amino acids (via the infamous peptide bond) as part of the peptide elongation process.

The step mentioned above which was incorrectly attributed to chloramphenicol is in fact the target for both clindamycin and the macrolides.

 

[hardee17]

I've done extensive research and the bottom line is that clinda has the same MOA as macrolides, in terms of step one.

peptidyltransferase: cholemphenicol
translocation: macrolides/clinda


PBPs are a different matter

 

[Transposony]

Hope this helps.

Mechanism of action: Chloramphenicol is a bacteriostatic drug that stops bacterial growth by inhibiting protein synthesis. Chloramphenicol prevents protein chain elongation by inhibiting the peptidyl transferase activity of the bacterial ribosome. It specifically binds to A2451 and A2452 residues in the 23S rRNA of the 50S ribosomal subunit, preventing peptide bond formation.[23] While chloramphenicol and the macrolide class of antibiotics both interact with ribosomes, chloramphenicol is not a macrolide. It directly interferes with substrate binding, whereas macrolides sterically block the progression of the growing peptide.

 

[Xamber]

I have a similar question to Stronghold's...I'm assuming that you are referring to FA 2013 p 181 where it says 'Chloramphenicol blocks peptidyltransferase' and 'Clindamycin blocks peptide transfer (transpeptidation).'

By definition, these are the same things - peptidyl transferase transfers the growing peptide chain to the newly-arrived AA-tRNA and forms a peptide bond between them (i.e. transpeptidation).

However, on p 179 of FA 2013, the figure shows that Clindamycin (and Macrolides) block translocation, which occurs after peptidyl transferase. So is FA only partly right? Does Clindamycin do BOTH - block peptidyl transferase/transpeptidation AND block translocation? I can envision Clindamycin's MOA as a combination of Chloramphenicol's and Macrolide's, but I would like clarification on how Step 1 will likely word it. Thanks

 

[stronghold]

Yes, Xamber. Those FA pages make me confused!