Structural characterization of aminoglycoside 4'-O-adenylyltransferase ANT(4')-IIb from Pseudomonas aeruginosa.

ABSTRACT: Aminoglycosides were one of the first classes of broad-spectrum antibacterial drugs clinically used to effectively combat infections. The rise of resistance to these drugs, mediated by enzymatic modification, has since compromised their utility as a treatment option, prompting intensive research into the molecular function of resistance enzymes. Here, we report the crystal structure of aminoglycoside nucleotidyltransferase ANT(4')-IIb in apo and tobramycin-bound forms at a resolution of 1.6 and 2.15 Å, respectively. ANT(4')-IIb was discovered in the opportunistic pathogen Pseudomonas aeruginosa and conferred resistance to amikacin and tobramycin. Analysis of the ANT(4')-IIb structures revealed a two-domain organization featuring a mixed β-sheet and an α-helical bundle. ANT(4')-IIb monomers

SUBMITTER: Semper C 

PROVIDER: S-EPMC7020987 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature