Structural basis for cross-resistance to ribosomal PTC antibiotics.

ABSTRACT: Clinically relevant antibiotics that target the ribosomal peptidyl transferase center (PTC), a highly conserved ribosomal region, exert their inhibitory action by exploiting the flexibility of PTC nucleotides, which trigger modulations of the shape of the antibiotic binding pocket. Resistance to these antibiotics was observed clinically and in vitro. Based on the crystal structures of the large ribosomal subunit from eubacterium suitable to represent pathogens in complex with these antibiotics, it was found that all nucleotides mediating resistance to PTC antibiotics cluster on one side of the PTC. Over half of the nucleotides affecting resistance reside in regions of lower sequence conservation, and are too distal to make Van der Waals interactions with the bound drugs. Alterations of the

SUBMITTER: Davidovich C 

PROVIDER: S-EPMC2605634 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature