School of Molecular Sciences, Arizona State University, Tempe, AZ 85281, United States; The Biodesign Center for Molecular Design and Biomimetics, Arizona State University, Tempe, AZ 85281, United States.
School of Molecular Sciences, Arizona State University, Tempe, AZ 85281, United States; The Biodesign Center for Molecular Design and Biomimetics, Arizona State University, Tempe, AZ 85281, United States.
Curr Opin Struct Biol. 2018 Aug;51:170-176. doi: 10.1016/j.sbi.2018.06.001. Epub 2018 Jul 3.
The ability to rationally design metalloproteins with desired functions remains a difficult challenge despite many years of effort. Recently, the potential of using genetically encoded metal-chelating non-canonical amino acids (NCAAs) to circumvent longstanding difficulties in this field has begun to be explored. In this review, we describe the development of this approach and its application to the rational design or directed evolution of NCAA-containing metalloproteins in which the bound metal ions serve in structural roles, as catalysts, or as regulators of the assembly or disassembly of protein complexes. These successes highlight the fact that amino acids not found in nature can recapitulate the functions of their naturally occurring counterparts and suggest the promise of this nascent approach for simplifying the metalloprotein design problem.
尽管经过多年的努力，理性设计具有预期功能的金属蛋白仍然是一个具有挑战性的难题。最近，人们开始探索利用遗传编码的金属螯合非天然氨基酸（NCAA）来规避该领域长期存在的困难。在这篇综述中，我们描述了这种方法的发展及其在含 NCAA 的金属蛋白的理性设计或定向进化中的应用，其中结合的金属离子在结构、催化或蛋白质复合物组装或拆卸的调节中发挥作用。这些成功突出表明，自然界中不存在的氨基酸可以再现其天然对应物的功能，并表明这种新兴方法在简化金属蛋白设计问题方面具有很大的潜力。
