Chemical Sciences Division , Lawrence Berkeley National Laboratory , Berkeley , California 94720 , United States.
J Am Chem Soc. 2019 Aug 14;141(32):12487-12492. doi: 10.1021/jacs.9b05323. Epub 2019 Aug 2.
We report the effect of conformational dynamics on the fluctuations of electric fields in the active site of the enzyme ketosteroid isomerase (KSI). While KSI is considered to be a rigid enzyme with little conformational variation to support different stages of the catalytic cycle, we show that KSI utilizes cooperative side chain motions of the entire protein scaffold outside the active site to modulate electric fields in the active site. We find that while the active site residues Asp-40 and Tyr-16 maintain their electric field contributions at all effective time scales, the conformational dynamics of a single active residue, Asp-103, promotes large electric field fluctuations that contribute to different stages of the catalytic cycle, including the catalytic step and product release.
我们报告构象动力学对酶酮甾体异构酶（KSI）活性位点中电场波动的影响。虽然 KSI 被认为是一种刚性酶，其构象变化很小，无法支持催化循环的不同阶段，但我们表明，KSI 利用整个蛋白质支架在活性位点之外的协同侧链运动来调节活性位点中的电场。我们发现，虽然活性位点残基 Asp-40 和 Tyr-16 在所有有效时间尺度上保持其电场贡献，但单个活性残基 Asp-103 的构象动力学促进了大的电场波动，这些波动有助于催化循环的不同阶段，包括催化步骤和产物释放。
