（stimulus）时，酶的活性增加（output）。（图片来源：Benkovic lab, Penn State）
美国科学家近日发现了一种新方法，能够利用光控制催化生化反应的某种蛋白活性。研究人员称，这是首次成功利用光来控制一种蛋白的活性，将来可能具有多种应用，比如用来关闭细胞中致病蛋白的活性等。相关论文发表在10月17日的《科学》（Science）杂志上。
美国德州大学西南医学中心的Rama Ranganathan和同事，通过将来自燕麦的光觉蛋白插入来自大肠杆菌的催化生化反应的酶，创造出了一种杂种蛋白。研究人员发现，向这个光觉蛋白照射光可操纵酶的活性。论文主要作者之一、美国宾夕法尼亚州立大学化学系的Stephen Benkovic说：“这一技术就像光开关，当我们向光觉蛋白照射光时，酶的活性增加；当关闭光时，酶的活性降低。”
研究人员表示，在设计杂种蛋白的时候，有几个重要的因素需要考虑。一个是蛋白的正确构象，错误构象将会使蛋白无法对光作出反应；一个是光觉蛋白插入酶的特定位点，位点错误同样会使光开关无法起作用。
研究小组未来将会研究由光触发的信号如何从光觉蛋白向酶传输。Benkovic说：“这一过程的作用机制尚不清楚，目前来看，其效果也较小。不过我们计划优化这一技术，看看是否能够以另一种方式利用光，来调节酶的活性。”（生物谷Bioon.com）
生物谷推荐原始出处：
Science，Vol. 322. no. 5900, pp. 438 – 442，Jeeyeon Lee，Rama Ranganathan
Surface Sites for Engineering Allosteric Control in Proteins
Jeeyeon Lee,1* Madhusudan Natarajan,2* Vishal C. Nashine,1 Michael Socolich,2 Tina Vo,2 William P. Russ,2 Stephen J. Benkovic,1 Rama Ranganathan2
Statistical analyses of protein families reveal networks of coevolving amino acids that functionally link distantly positioned functional surfaces. Such linkages suggest a concept for engineering allosteric control into proteins: The intramolecular networks of two proteins could be joined across their surface sites such that the activity of one protein might control the activity of the other. We tested this idea by creating PAS-DHFR, a designed chimeric protein that connects a light-sensing signaling domain from a plant member of the Per/Arnt/Sim (PAS) family of proteins with Escherichia coli dihydrofolate reductase (DHFR). With no optimization, PAS-DHFR exhibited light-dependent catalytic activity that depended on the site of connection and on known signaling mechanisms in both proteins. PAS-DHFR serves as a proof of concept for engineering regulatory activities into proteins through interface design at conserved allosteric sites.
1 Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA.
2 Green Center for Systems Biology and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
