Antibiotics and inhibition of protein synthesis

Protein synthesis can be divided into

• a- Steps taking place prior to translation• b- Steps in the translation at

the ribosomes.

Activation of the amino acids

B- translation of mRNA on ribosomes

• Bacterial ribosomes are characterized by their sedimentation rate of 70 S ribosomes. The 70 S dissociate to 50 S and 30 S.

• Protein biosynthesis at the ribosomal levels can be classified into:

1. The initiation phase allows the start of protein synthesis

2. Elongation phase of the peptide by one amino acid at each cycle.

3. Termination phase which stops protein synthesis (presence of non-sense codon.

Role of antibiotics in inhibition of bacterial protein synthesis

Inhibition of aminoacyl-tRNA formation:

• - Both reactions are catalyzed by amino acid specific ligases.

- Indolmycin competes with tryptophan in the activation reaction (i.e no enzym-tryptophaneacyl-AMP

• - Furanomycin competes with isoleucine and inhibit the transfer reaction

Tetracyclin antibiotic

inhibits tRNA binding to

ribosomes thus inhibits

protein synthesis.

Inhibition of initiation stage:

• Viomycin antibiotic prevents mRNA binding to the 30 s subunit rather than binding to tRNA

Aminoglycosides:• streptomycin inhibits initiation reaction.

• Neomycin and kanamycin inhibits translocation of the ribosome along mRNA.

Inhibition of elongation

- Microlides: erythromycin inhibits

peptide chain elongation.

- Chloramphincol inhibits peptidyl- transfer reaction.

Inhibition of termination

• E.g Puromycin is an analogue of the 3´-end of the aminoacyl-tRNA.

• Peptidyltransferase can not cleave the amide bridge with pauromycin in contrast to the ester bond of peptidyl-tRNA.