title: Protein dynamics are influenced by the order of ligand binding to an antibiotic resistance enzyme.
abstract: The aminoglycoside N3 acetyltransferase-IIIb (AAC) is responsible for conferring bacterial resistance to a variety of aminoglycoside antibiotics. Nuclear magnetic resonance spectroscopy and dynamic light scattering analyses revealed a surprising result; the dynamics of the ternary complex between AAC and its two ligands, an antibiotic and coenzyme A, are dependent upon the order in which the ligands are bound. Additionally, two structurally similar aminoglycosides, neomycin and paromomycin, induce strikingly different dynamic properties when they are in their ternary complexes. To the best of our knowledge, this is the first example of a system in which two identically productive pathways of forming a simple ternary complex yield significant differences in dynamic properties. These observations emphasize the importance of the sequence of events in achieving optimal protein-ligand interactions and demonstrate that even a minor difference in molecular structure can have a profound effect on biochemical processes.
authors: Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee , Knoxville, Tennessee 37996, United States.
authors: Adrianne L
authors: AL
authors: Norris
authors: Jonathan
authors: J
authors: Nickels
authors: Alexei P
authors: AP
authors: Sokolov
authors: Engin H
authors: EH
authors: Serpersu
mesh_terms: D000123:Acetyltransferases / Q000737:chemistry*; D000617:Aminoglycosides / Q000737:chemistry; D003065:Coenzyme A / Q000737:chemistry*; D008024:Ligands; D008027:Light; D009355:Neomycin / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010303:Paromomycin / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D012542:Scattering, Radiation; D013816:Thermodynamics
chemical_list: D000617:Aminoglycosides; D008024:Ligands; D010303:Paromomycin; D000123:Acetyltransferases; C045539:aminoglycoside N(3')-acetyltransferase; D009355:Neomycin; D003065:Coenzyme A