Coenzyme A binding to the aminoglycoside acetyltransferase (3)-IIIb increases conformational sampling of antibiotic binding site.
NMR spectroscopy experiments and molecular dynamics simulations were performed to describe the dynamic properties of the aminoglycoside acetyltransferase (3)-IIIb (AAC) in its apo and coenzyme A (CoASH) bound forms. The (15)N-(1)H HSQC spectra indicate a partial structural change and coupling of the CoASH binding site with another region in the protein upon the CoASH titration into the apo enzyme. Molecular dynamics simulations indicate a significant structural and dynamic variation of the long loop in the antibiotic binding domain in the form of a relatively slow (250 ns), concerted opening motion in the CoASH-enzyme complex and that binding of the CoASH increases the structural flexibility of the loop, leading to an interchange between several similar equally populated conformations.
UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830, United States.
Xiaohu
X
Hu
Adrianne L
AL
Norris
Jerome
J
Baudry
Engin H
EH
Serpersu
D000123:Acetyltransferases / Q000737:chemistry*; D000617:Aminoglycosides / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001059:Apoproteins / Q000737:chemistry; D001408:Bacillus anthracis / Q000201:enzymology*; D001665:Binding Sites; D003065:Coenzyme A / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D055672:Static Electricity; D013379:Substrate Specificity; D013816:Thermodynamics
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001059:Apoproteins; D000123:Acetyltransferases; C019681:aminoglycoside acetyltransferase; D003065:Coenzyme A