1 Antimicrobials that Bind to the 50S Ribosomal Subunit Chloramphenicol , Lincomycin, Clindamycin (bacteriostatic) • Mode of action - These antimicrobials bind to the 50S ribosome and inhibit peptidyl transferase activity. • Spectrum of activity - Chloramphenicol - Broad range; Lincomycin and clindamycin - Restricted range • Resistance - Common • Adverse effects - Chloramphenicol is toxic (bone marrow suppression) but is used in the treatment of bacterial meningitis.
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Antimicrobials that Bind to the 50S Ribosomal Subunit · 2016-02-12 · 1 Antimicrobials that Bind to the 50S Ribosomal Subunit Chloramphenicol, Lincomycin, Clindamycin (bacteriostatic)
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Antimicrobials that Bind to the 50SRibosomal Subunit
Journal of Molecular BiologyVolume 330, Issue 5 , 25 July 2003, Pages 1061-1075
Structures of Five Antibiotics Bound at the PeptidylTransferase Center of the Large Ribosomal Subunit
Jeffrey L. Hansen1, Peter B. Moore1, 2 and Thomas A. Steitz, , 1, 2, 3
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Anisomycin, chloramphenicol, sparsomycin, blasticidin S, and virginiamycin Mbind to sites that overlap those of either peptidyl-tRNA or aminoacyl-tRNA, consistent with their functioning as competitive inhibitors ofpeptide bond formation.
Two hydrophobic crevices, one at the peptidyl transferase center and the otherat the entrance to the peptide exit tunnel play roles in binding these antibiotics.
Midway between these crevices, nucleotide A2103 of H. marismortui (2062Escherichia coli) varies in its conformation and thereby contacts antibioticsbound at either crevice.
The aromatic ring of anisomycin binds to the active-site hydrophobiccrevice, as does the aromatic ring of puromycin, while the aromatic ringof chloramphenicol binds to the exit tunnel hydrophobic crevice.
Sparsomycin contacts primarily a P-site bound substrate, but alsoextends into the active-site hydrophobic crevice.
Virginiamycin M occupies portions of both the A and P-site, and induces aconformational change in the ribosome.
Blasticidin S base-pairs with the P-loop and thereby mimics C74and C75 of a P-site bound tRNA.