Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee , Knoxville, Tennessee 37996, United States.
Biochemistry. 2014 Jan 14;53(1):30-8. doi: 10.1021/bi401635r. Epub 2013 Dec 24.
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.
氨基糖苷 N3 乙酰转移酶-IIIb（AAC）负责赋予细菌对多种氨基糖苷抗生素的耐药性。核磁共振波谱和动态光散射分析揭示了一个令人惊讶的结果；AAC 与其两个配体（抗生素和辅酶 A）的三元复合物的动力学取决于配体结合的顺序。此外，两种结构相似的氨基糖苷类抗生素，新霉素和巴龙霉素，当其处于三元复合物中时，会引起明显不同的动态性质。据我们所知，这是第一个例子，其中两个相同的形成简单三元复合物的生产途径产生显著差异的动态特性。这些观察结果强调了在实现最佳蛋白质-配体相互作用时事件顺序的重要性，并表明即使分子结构的微小差异也会对生化过程产生深远影响。
