New functions from old scaffolds: how nature reengineers enzymes for new functions.

Publisher Summary This chapter describes how nature has reengineered some protein scaffolds for a range of functions by examining a small number of example superfamilies. The goal is to illustrate on how organizing very distantly related proteins into superfamilies provides a useful context for understanding evolutionary protein engineering, that cannot be achieved by even the most elegant analysis of single proteins, one at a time. The chapter discusses the three enzyme superfamilies, the enolase, vicinal oxygen chelate fold (VOC), and haloacid dehalogenase (HAD) superfamilies, that effectively exemplify some of the different types of structural engineering that nature has employed over the course of evolution. The enolase superfamily scaffold is an α/β barrel, one of the most common and best characterized fold types in all of biology. Analysis of protein superfamilies through explicit mapping of common functional characteristics to conserved structural elements among very distantly related homologs provides a valuable conceptual approach to connecting sequence, structure, and function in ways that are important for understanding both natural and laboratory-based protein engineering.

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