Tigecycline, a glycylcycline, overcomes tetracycline efflux pump resistance. At which ribosomal location does tigecycline bind with 5-fold higher affinity than minocycline, explaining its activity against Tet(M)-harboring organisms?
- A 50S ribosomal subunit near the peptidyl transferase centre, mimicking chloramphenicol binding
- B Secondary binding site on 50S subunit at the L3/L4 protein interface
- C Primary binding site on 30S ribosomal subunit (h34 helix of 16S rRNA), blocking A-site tRNA accommodation with steric hindrance from the 9-t-butyl-glycylamido substituent ✓
- D Initiator tRNA fMet-tRNA binding site on the P-site of 70S ribosome
Explanation
Tigecycline binds the primary tetracycline binding site on the 30S ribosomal subunit at helix 34 (h34) of 16S rRNA, blocking accommodation of aminoacyl-tRNA in the ribosomal A-site. The bulky 9-tert-butylglycylamido substituent at C-9 of the glycylcycline ring system produces steric clashes that prevent ribosomal protection proteins Tet(M) and Tet(O) — which normally displace tetracyclines from their binding site via GTPase activity — from acting on tigecycline. This explains why tigecycline overcomes both efflux-mediated and ribosomal-protection-based tetracycline resistance. It does not bind the peptidyl transferase centre or 50S subunit.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.