De Novo Cytochrome Design: Bioinspired Proteins as Tools for Interrogating and Manipulating Biological Electron Transfer
摘要
All members of the NADPH oxidase (NOX) family contain a helical transmembrane domain that binds two b-type hemes facilitating cross-membrane electron transport and reactive oxygen species (ROS) production. The diheme four-helix bundle at the core of this domain represents a common motif used by numerous protein families across nature to transport electrons across membranes. Inspired by its simplicity and versatility, protein designers have created artificial proteins based upon this motif to study the fundamentals of electron transfer and build their own redox-active de novo cytochromes from scratch. This chapter first discusses the prevalence of the diheme four-helix bundle architecture in natural proteins, then provides a historical overview of de novo designed cytochromes and finally outlines the design and characterization of a suite of modular artificial cytochromes that can be engineered with atomic precision.