Alavi Zahra, Zocchi Giovanni
Department of Physics and Astronomy, University of California Los Angeles, Los Angeles, California 90095, USA.
Department of Physics and Astronomy, Loyola Marymount University Los Angeles, Los Angeles, California 90095, USA.
Phys Rev E. 2018 May;97(5-1):052402. doi: 10.1103/PhysRevE.97.052402.
Pursuing a materials science approach to understanding the deformability of enzymes, we introduce measurements of the phase of the mechanical response function within the nanorheology paradigm. Driven conformational motion of the enzyme is dissipative as characterized by the phase measurements. The dissipation originates both from the surface hydration layer and the interior of the molecule, probed by examining the effect of point mutations on the mechanics. We also document changes in the mechanics of the enzyme examined, guanylate kinase, upon binding its four substrates. GMP binding stiffens the molecule, ATP and ADP binding softens it, while there is no clear mechanical signature of GDP binding. A hyperactive two-Gly mutant is found to possibly trade specificity for speed. Global deformations of enzymes are shown to be dependent on both hydration layer and polypeptide chain dynamics.
我们采用材料科学的方法来理解酶的可变形性，引入了纳米流变学范式下机械响应函数相位的测量。酶的驱动构象运动是耗散性的，这由相位测量所表征。这种耗散既源于表面水化层，也源于分子内部，通过研究点突变对力学的影响来探究。我们还记录了所研究的鸟苷酸激酶在结合其四种底物时力学性质的变化。GMP结合使分子变硬，ATP和ADP结合使其变软，而GDP结合没有明显的力学特征。发现一种高活性的双甘氨酸突变体可能以特异性换取速度。结果表明，酶的整体变形取决于水化层和多肽链动力学。
