Molecular recognition of aminoglycoside antibiotics by bacterial defence proteins: NMR study of the structural and conformational features of streptomycin inactivation by Bacillus subtilis aminoglycoside-6-adenyl transferase.
The molecular recognition of streptomycin by Bacillus subtilis aminoglycoside-6-adenyl transferase has been analysed by a combination of NMR techniques and molecular dynamic simulations. This protein inactivates streptomycin by transferring an adenyl group to position six of the streptidine moiety. Our combined approach provides valuable information about the bioactive conformation for both the antibiotic and ATP and shows that the molecular recognition process for streptomycin involves a conformational selection phenomenon. The binding epitope for both ligands has also been analysed by 1D-STD experiments. Finally, the specificity of the recognition process with respect to the aminoglycoside and to the nucleotide has been studied.
Instituto de Química Orgánica, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
Francisco
F
Corzana
Igor
I
Cuesta
Agatha
A
Bastida
Ana
A
Hidalgo
Montserrat
M
Latorre
Carlos
C
González
Eduardo
E
García-Junceda
Jesús
J
Jiménez-Barbero
Juan Luis
JL
Asensio
D000617:Aminoglycosides / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000201:enzymology*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D013307:Streptomycin / Q000737:chemistry / Q000494:pharmacology*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D013307:Streptomycin