A sparsomycin-resistant mutant of Halobacterium salinarium lacks a modification at nucleotide U2603 in the peptidyl transferase centre of 23 S rRNA.
Sparsomycin, a broad-spectrum antibiotic, acts at the peptidyl transferase centre of the ribosome, stabilizing peptidyl-tRNA binding at the P-site and weakening ternary complex binding. A sparsomycin-resistant mutant was isolated for the archaeon Halobacterium salinarium and shown to lack a post-transcriptional modification of U2603 (Escherichia coli numbering U2584), which is a universally conserved uridine base located within the peptidyl transferase loop of 23 S rRNA. This mutant also exhibited altered sensitivities to the peptidyl transferase antibiotics anisomycin, chloramphenicol and puromycin. Several lines of evidence indicate that the unmodified uridine base lies within the P-substrate site of the peptidyl transferase centre.
Lázaro
E
E
Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
Rodriguez-Fonseca
C
C
Porse
B
B
Ureña
D
D
Garrett
R A
RA
Ballesta
J P
JP
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites; D006217:Halobacterium / Q000187:drug effects* / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009690:Nucleic Acid Conformation; D010458:Peptidyl Transferases; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012323:RNA Processing, Post-Transcriptional; D012338:RNA, Ribosomal, 23S / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012360:RNA, Transfer, Phe; D012270:Ribosomes / Q000187:drug effects; D017423:Sequence Analysis, RNA; D013033:Sparsomycin / Q000494:pharmacology*; D014529:Uridine / Q000737:chemistry
D000900:Anti-Bacterial Agents; D011500:Protein Synthesis Inhibitors; D012338:RNA, Ribosomal, 23S; D012360:RNA, Transfer, Phe; D013033:Sparsomycin; D010458:Peptidyl Transferases; D014529:Uridine