4b3m
Crystal structure of the 30S ribosome in complex with compound 1Crystal structure of the 30S ribosome in complex with compound 1
Structural highlights
FunctionRS14Z_THET8 Required for the assembly of 30S particles and may also be responsible for determining the conformation of the 16S rRNA at the A site (By similarity). Binds 16S rRNA in center of the 30S subunit head.[HAMAP-Rule:MF_01364_B] Publication Abstract from PubMedClinical use of 2-deoxystreptamine aminoglycoside antibiotics, which target the bacterial ribosome, is compromised by adverse effects related to limited drug selectivity. Here we present a series of 4',6'-O-acetal and 4'-O-ether modifications on glucopyranosyl ring I of aminoglycosides. Chemical modifications were guided by measuring interactions between the compounds synthesized and ribosomes harbouring single point mutations in the drug-binding site, resulting in aminoglycosides that interact poorly with the drug-binding pocket of eukaryotic mitochondrial or cytosolic ribosomes. Yet, these compounds largely retain their inhibitory activity for bacterial ribosomes and show antibacterial activity. Our data indicate that 4'-O-substituted aminoglycosides possess increased selectivity towards bacterial ribosomes and little activity for any of the human drug-binding pockets. 4'-O-substitutions determine selectivity of aminoglycoside antibiotics.,Perez-Fernandez D, Shcherbakov D, Matt T, Leong NC, Kudyba I, Duscha S, Boukari H, Patak R, Dubbaka SR, Lang K, Meyer M, Akbergenov R, Freihofer P, Vaddi S, Thommes P, Ramakrishnan V, Vasella A, Bottger EC Nat Commun. 2014 Jan 28;5:3112. doi: 10.1038/ncomms4112. PMID:24473108[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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