Protein Synthesis Inhibitors

Several Antibiotic and Toxin inhibitors of Translation

Tetracyclines: Inhibits protein synthesis by binding to the subunit of the bacterial ribosome (30S –Small subunit).

Structure of tetracycline

Streptomycin: Binds the 30S ribosomal subunit of the tuberculosis bacterium and prevents the ribosome from forming the complex necessary to initiate protein translation. Streptomycin is the first line of chemical defense against Mycobacterium tuberculosis.

Neomycin: similar in activity to streptomycin

Fusidic acid: similar to erythromycin only by preventing EFG from dissociating from the large subunit and blocks translocation.

Chloramphenicol: Blocks formation of new peptide bonds during protein synthesis by binding to the 50S subunit (50S-Large subunit) of the ribosome.
Structure of chloramphenicol

Erthromycin (Macrolides): Binds the 50S subunit (large subunit) and blocks translocation of the new protein on the ribosome, thus effectively halting synthesis.

Clindamycin (Lincosamides): Inhibits protein synthesis by binding to a subunit of the bacterial ribosome(50S).

Aminoglycosides: inhibit nucleic acid or protein synthesis in bacteria. They are L-shaped molecules that fit into L-shaped pockets of bacterial ribosomal RNA. When they insert themselves into rRNA, they disrupt ribosomal structure. They don’t have this effect on human cells because the L-shaped pocket is specific to bacteria.

Linezolid: Binds rRNA to prevent translation initiation and thus protein synthesis.

Puromycin: Resembles an aminoacyl-tRNA, interferes with peptide transfer resulting in premature termination in both prokaryotes and eukaryotes.

Ricin: Found in castor (Ricinus) beans, catalyzes cleavage of the eukaryotic large subunit rRNA.

Cycloheximide : Inhibits eukaryotic peptidyltransferase
Structure of cycloheximide

Diphtheria (diptheria) toxin:

ADP-ribosylated diphthamide (dipthamide) residue
ADP-ribosylated diphthamide (dipthamide) residue
Protein from Corynebacterium diphtheriae which which causes diphtheria (diptheria); catalyzes ADP-ribosylation and inactivation of eEF-2; eEF-2 contains a modified His residue known as diphthamide (dipthamide), it is this resudue that is the target of the toxin.
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