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Structure paper

TitleMacrolones target bacterial ribosomes and DNA gyrase and can evade resistance mechanisms.
Journal, issue, pagesNat. Chem. Biol., Year 2024
Publish dateJan 27, 2024 (structure data deposition date)
AuthorsAleksandrova, E.V. / Ma, C.X. / Klepacki, D. / Alizadeh, F. / Vazquez-Laslop, N. / Liang, J.H. / Polikanov, Y.S. / Mankin, A.S.
External linksNat. Chem. Biol. / PubMed:39039256
MethodsX-ray diffraction
Resolution2.35 - 2.6 Å
Structure data

PDB-8vtu:
Crystal structure of the wild-type Thermus thermophilus 70S ribosome in complex with macrolone MCX-66, mRNA, aminoacylated A-site Phe-tRNAphe, aminoacylated P-site fMet-tRNAmet, and deacylated E-site tRNAphe at 2.40A resolution
Method: X-RAY DIFFRACTION / Resolution: 2.4 Å

PDB-8vtv:
Crystal structure of the wild-type Thermus thermophilus 70S ribosome in complex with macrolone MCX-91, mRNA, aminoacylated A-site Phe-tRNAphe, aminoacylated P-site fMet-tRNAmet, and deacylated E-site tRNAphe at 2.55A resolution
Method: X-RAY DIFFRACTION / Resolution: 2.55 Å

PDB-8vtw:
Crystal structure of the wild-type Thermus thermophilus 70S ribosome in complex with macrolone MCX-128 and protein Y at 2.35A resolution
Method: X-RAY DIFFRACTION / Resolution: 2.35 Å

PDB-8vtx:
Crystal structure of the A2058-N6-dimethylated Thermus thermophilus 70S ribosome in complex with macrolone MCX-128, mRNA, aminoacylated A-site Phe-tRNAphe, aminoacylated P-site fMet-tRNAmet, and deacylated E-site tRNAphe at 2.40A resolution
Method: X-RAY DIFFRACTION / Resolution: 2.4 Å

PDB-8vty:
Crystal structure of the wild-type Thermus thermophilus 70S ribosome in complex with ciprofloxacin and protein Y at 2.60A resolution
Method: X-RAY DIFFRACTION / Resolution: 2.6 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-K:
Unknown entry

PDB-1aez:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-SF4:
IRON/SULFUR CLUSTER

ChemComp-PHE:
PHENYLALANINE

ChemComp-FME:
N-FORMYLMETHIONINE

ChemComp-HOH:
WATER

PDB-1ae0:
Unknown entry

PDB-1ae1:
TROPINONE REDUCTASE-I COMPLEX WITH NADP

ChemComp-ARG:
ARGININE

ChemComp-MPD:
(4S)-2-METHYL-2,4-PENTANEDIOL / precipitant*YM

ChemComp-CPF:
1-CYCLOPROPYL-6-FLUORO-4-OXO-7-PIPERAZIN-1-YL-1,4-DIHYDROQUINOLINE-3-CARBOXYLIC ACID / antibiotic*YM

Source
  • escherichia coli (E. coli)
  • thermus thermophilus hb8 (bacteria)
  • escherichia phage t4 (virus)
  • escherichia coli k-12 (bacteria)
KeywordsRIBOSOME / Macrolone; macrolide; fluoroquinolone; erythromycin; ciprofloxacin; antibiotic; 70S ribosome; X-ray structure; inhibition of translation; peptidyl transferase center; nascent peptide exit tunnel; multidrug; resistance; methylation; 23S rRNA; A2058; ERM / RIBOSOME/ANTIBIOTIC / RIBOSOME-ANTIBIOTIC complex

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