Ribosome as Drug Target:
Many clinically important antibiotics specifically inhibit bacterial (70S) ribosomes without affecting eukaryotic (80S) ribosomes, exploiting structural differences:
| Antibiotic | Target | Mechanism |
|---|---|---|
| Streptomycin | 30S subunit | Misreads codons, causes premature termination |
| Tetracycline | 30S A-site | Blocks aminoacyl-tRNA entry |
| Chloramphenicol | 50S peptidyl transferase | Blocks peptide bond formation |
| Erythromycin | 50S translocation | Blocks ribosome movement along mRNA |
| Puromycin | Both 70S and 80S A-site | Mimics aminoacyl-tRNA, causes premature release |
Alpha-Amanitin (Toxin from Death Cap Mushroom):
- Low dose: inhibits eukaryotic RNA Polymerase II (blocks mRNA synthesis)
- High dose: also inhibits RNA Polymerase III
- Does NOT affect RNA Polymerase I (rRNA synthesis)
- Mechanism: physical obstruction of the RNA exit channel
Sickle Cell Anemia — Molecular Level:
GAG (Glu) → GUG (Val) in codon 6 of beta-globin → missense mutation → valine replaces glutamate → HbS polymerizes under low oxygen → sickle-shaped RBCs → clinical disease