Nguyen Vy, Wilson Christopher, Hoemberger Marc, Stiller John B, Agafonov Roman V, Kutter Steffen, English Justin, Theobald Douglas L, Kern Dorothee
Howard Hughes Medical Institute and Department of Biochemistry, Brandeis University, Waltham, MA 02452, USA.
Department of Biochemistry, Brandeis University, Waltham, MA 02452, USA.
Science. 2017 Jan 20;355(6322):289-294. doi: 10.1126/science.aah3717. Epub 2016 Dec 22.
With early life likely to have existed in a hot environment, enzymes had to cope with an inherent drop in catalytic speed caused by lowered temperature. Here we characterize the molecular mechanisms underlying thermoadaptation of enzyme catalysis in adenylate kinase using ancestral sequence reconstruction spanning 3 billion years of evolution. We show that evolution solved the enzyme's key kinetic obstacle-how to maintain catalytic speed on a cooler Earth-by exploiting transition-state heat capacity. Tracing the evolution of enzyme activity and stability from the hot-start toward modern hyperthermophilic, mesophilic, and psychrophilic organisms illustrates active pressure versus passive drift in evolution on a molecular level, refutes the debated activity/stability trade-off, and suggests that the catalytic speed of adenylate kinase is an evolutionary driver for organismal fitness.
由于早期生命可能存在于高温环境中，酶必须应对因温度降低而导致的催化速度固有下降。在这里，我们利用跨越30亿年进化历程的祖先序列重建，表征了腺苷酸激酶中酶催化热适应的分子机制。我们表明，进化通过利用过渡态热容量解决了该酶的关键动力学障碍，即在更凉爽的地球上如何维持催化速度。追踪从热启动状态到现代超嗜热、嗜温和嗜冷生物的酶活性和稳定性的演变，揭示了分子水平进化中的主动压力与被动漂移，驳斥了有争议的活性/稳定性权衡，并表明腺苷酸激酶的催化速度是生物体适应性的进化驱动力。
