Characterization of GE82832, a peptide inhibitor of translocation interacting with bacterial 30S ribosomal subunits.
GE82832, a secondary metabolite produced by Streptosporangium cinnabarinum (strain GE82832), has been identified as a translational inhibitor by in vitro screening of a library of natural products. Secondary functional tests specific for individual steps of the translational pathway demonstrated that translocation is the specific target of GE82832. Chemical probing in situ demonstrated that this antibiotic protects bases A1324 and A1333 and exposes C1336 of 16S rRNA, thereby indicating that its binding site is located on the head of the 30S ribosomal subunit. The ribosomal location of GE82832, near ribosomal protein S13 and G1338, two elements of the small subunit that are part of or close to the B1a intrasubunit bridge, suggests that translocation inhibition results from an altered dynamics of 30S-50S ribosomal subunit interaction.
Brandi
Letizia
L
Laboratory of Genetics, Department of Biology MCA, University of Camerino, Italy.
Fabbretti
Attilio
A
Di Stefano
Michele
M
Lazzarini
Ameriga
A
Abbondi
Monica
M
Gualerzi
Claudio O
CO
D000192:Actinomycetales / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects; D011487:Protein Conformation; D021381:Protein Transport / Q000187:drug effects*; D011691:Puromycin / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism
D001426:Bacterial Proteins; C512383:GE82832 peptide, Streptosporangium cinnabarinum; D010455:Peptides; D012269:Ribosomal Proteins; C040469:ribosomal protein S30; D011691:Puromycin