Antibiotics and inhibition of protein synthesis

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 enzymtryptophaneacyl-AMP
• - Furanomycin competes with isoleucine and
inhibit the transfer reaction
Tetracyclin
inhibits
antibiotic
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 peptidyltransfer 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.