Effect of solvent and protein dynamics in ligand recognition and inhibition of aminoglycoside adenyltransferase 2″-Ia.

ABSTRACT: The aminoglycoside modifying enzyme (AME) ANT(2″)-Ia is a significant target for next generation antibiotic development. Structural studies of a related aminoglycoside-modifying enzyme, ANT(3″)(9), revealed this enzyme contains dynamic, disordered, and well-defined segments that modulate thermodynamically before and after antibiotic binding. Characterizing these structural dynamics is critical for in situ screening, design, and development of contemporary antibiotics that can be implemented in a clinical setting to treat potentially lethal, antibiotic resistant, human infections. Here, the first NMR structural ensembles of ANT(2″)-Ia are presented, and suggest that ATP-aminoglycoside binding repositions the nucleotidyltransferase (NT) and C-terminal domains for catalysis to efficiently occ

SUBMITTER: Bacot-Davis VR 

PROVIDER: S-EPMC5563142 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature