Metalloproteins catalyze numerous biological reactions ranging from photosynthesis, respiration, nitrogen fixation to signal transduction and complex chemical reactions. It is thus not surprising that metalloproteins account for almost one-half of the total number of proteins in nature. A considerable effort has been directed toward understanding the structure–function relationships using native proteins. However, it is an ultimate challenge to design metalloproteins using only the minimal features required to reproduce their functionalities as well as confer them with novel and unprecedented functionalities learned from the design process. In this chapter, we review some recent successes in the field of metalloprotein design using either de novo designed or native protein scaffolds. Furthermore, metalloprotein design employing unnatural amino acids or non-native cofactor are summarized. Finally, methodologies employing rational design, combinatorial selection, or both methods are also discussed.
Notes: Book chapter