Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Faraday Discuss. 2011;148:443-8. doi: 10.1039/c005523a.
Fundamental research into bioinorganic catalysis of the kind presented at this Faraday Discussion has the potential to turn inspiration drawn from impressive natural energy and chemical transformations into artificial catalyst constructions useful to mankind. Creating bio-inspired artificial constructions requires a level of understanding well beyond simple description of structures and mechanisms of natural enzymes. To be useful, such description must be augmented by a practical sense of structural and energetic engineering tolerances of the mechanism. Significant barriers to achieving an engineering understanding of enzyme mechanisms arise from natural protein complexity. In certain cases we can surmount these barriers to understanding, such as natural electron tunneling, coupling of electron tunneling to light capture and proton exchange as well as simpler bond breaking redox catalysis. Hope for similar solutions of more complex bioinorganic enzymes is indicated in several papers presented in this Discussion. Armed with an engineering understanding of mechanism, the current serious frustrations to successful creation of functional artificial proteins that are rooted in protein complexity can fall away. Here we discuss the genetic and biological roots of protein complexity and show how to dodge and minimize the effects of complexity. In the best-understood cases, artificial enzymes can be designed from scratch using the simplest of protein scaffolds.
这种类型的生物无机催化基础研究有可能将从令人印象深刻的自然能量和化学转化中获得的灵感转化为对人类有用的人工催化剂结构。创造受生物启发的人工结构需要超越对天然酶结构和机制的简单描述的理解水平。为了有用，这种描述必须通过对机制的结构和能量工程容差的实际感来增强。实现对酶机制的工程理解的重大障碍来自天然蛋白质的复杂性。在某些情况下，我们可以克服对这些理解的障碍，例如天然电子隧穿、电子隧穿与光捕获和质子交换的耦合以及更简单的断键氧化还原催化。在本次讨论中提交的几篇论文表明，对更复杂的生物无机酶有类似解决方案的希望。有了对机制的工程理解，目前由于蛋白质复杂性而导致成功创建功能性人工蛋白质的严重挫折就可以消除。在这里，我们讨论了蛋白质复杂性的遗传和生物学根源，并展示了如何回避和最小化复杂性的影响。在了解最透彻的情况下，可以使用最简单的蛋白质支架从头开始设计人工酶。
