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TitleStructure of ribosome-bound azole-modified peptide phazolicin rationalizes its species-specific mode of bacterial translation inhibition.
Journal, issue, pagesNat Commun, Vol. 10, Issue 1, Page 4563, Year 2019
Publish dateOct 8, 2019
AuthorsDmitrii Y Travin / Zoe L Watson / Mikhail Metelev / Fred R Ward / Ilya A Osterman / Irina M Khven / Nelli F Khabibullina / Marina Serebryakova / Peter Mergaert / Yury S Polikanov / Jamie H D Cate / Konstantin Severinov /
PubMed AbstractRibosome-synthesized post-translationally modified peptides (RiPPs) represent a rapidly expanding class of natural products with various biological activities. Linear azol(in)e-containing peptides ...Ribosome-synthesized post-translationally modified peptides (RiPPs) represent a rapidly expanding class of natural products with various biological activities. Linear azol(in)e-containing peptides (LAPs) comprise a subclass of RiPPs that display outstanding diversity of mechanisms of action while sharing common structural features. Here, we report the discovery of a new LAP biosynthetic gene cluster in the genome of Rhizobium Pop5, which encodes the precursor peptide and modification machinery of phazolicin (PHZ) - an extensively modified peptide exhibiting narrow-spectrum antibacterial activity against some symbiotic bacteria of leguminous plants. The cryo-EM structure of the Escherichia coli 70S-PHZ complex reveals that the drug interacts with the 23S rRNA and uL4/uL22 proteins and obstructs ribosomal exit tunnel in a way that is distinct from other compounds. We show that the uL4 loop sequence determines the species-specificity of antibiotic action. PHZ expands the known diversity of LAPs and may be used in the future as biocontrol agent for agricultural needs.
External linksNat Commun / PubMed:31594941 / PubMed Central
MethodsEM (single particle)
Resolution2.87 Å
Structure data

EMDB-20638, PDB-6u48:
E. coli 50S with phazolicin (PHZ) bound in exit tunnel
Method: EM (single particle) / Resolution: 2.87 Å

Source
  • escherichia coli (E. coli)
  • rhizobium sp. pop5 (bacteria)
KeywordsRIBOSOME/INHIBITOR / ribosome / phazolicin / antimicrobial protein / RIBOSOME-INHIBITOR complex

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