Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Angew Chem Int Ed Engl. 2018 Apr 3;57(15):3954-3957. doi: 10.1002/anie.201712757. Epub 2018 Jan 26.
Protein design is a useful strategy to interrogate the protein structure-function relationship. We demonstrate using a highly modular 3-stranded coiled coil (TRI-peptide system) that a functional type 2 copper center exhibiting copper nitrite reductase (NiR) activity exhibits the highest homogeneous catalytic efficiency under aqueous conditions for the reduction of nitrite to NO and H O. Modification of the amino acids in the second coordination sphere of the copper center increases the nitrite reductase activity up to 75-fold compared to previously reported systems. We find also that steric bulk can be used to enforce a three-coordinate Cu in a site, which tends toward two-coordination with decreased steric bulk. This study demonstrates the importance of the second coordination sphere environment both for controlling metal-center ligation and enhancing the catalytic efficiency of metalloenzymes and their analogues.
蛋白质设计是一种研究蛋白质结构-功能关系的有用策略。我们使用高度模块化的三股螺旋卷曲螺旋（TRI-肽系统）证明，在水相条件下，具有铜亚硝酸盐还原酶（NiR）活性的功能性 2 型铜中心对亚硝酸盐还原为 NO 和 H2O 的均相催化效率最高。与以前报道的系统相比，对铜中心第二配位球中氨基酸的修饰将亚硝酸盐还原酶活性提高了 75 倍。我们还发现，空间位阻可以用来强制在一个位点形成三配位的 Cu，而在空间位阻减小的情况下，Cu 倾向于形成二配位。这项研究表明，第二配位球环境对于控制金属中心的配位以及提高金属酶及其类似物的催化效率都非常重要。
