New insights about enzyme evolution from large scale studies of sequence and structure relationships.
Bottom Line: Here, we describe evolution of functionally diverse enzyme superfamilies, each representing a large set of sequences that evolved from a common ancestor and that retain conserved features of their structures and active sites.Using several examples, we describe the different structural strategies nature has used to evolve new reaction and substrate specificities in each unique superfamily.The results provide insight about enzyme evolution that is not easily obtained from studies of one or only a few enzymes.
Affiliation: From the Departments of Bioengineering and Therapeutic Sciences and.Show MeSH
Mentions: Reflecting this relatively new approach, sequence similarity networks are used in some figures in this review (see Figs. 1 and 4) to enable exploration of structure-function relationships in enzyme superfamilies from a large scale perspective. In these networks, nodes represent one or more proteins, and edges between them represent a measure of sequence or structural similarity. Although not a substitute for phylogenetic trees, similarity networks provide several advantages over trees and multiple alignments for developing new hypotheses about the evolution of functional features in superfamilies. They are quick to construct, do not require an accurate multiple sequence alignment, and can summarize in one network relationships among thousands of sequences. The networks can also be visualized and interactively manipulated and explored using such software packages as Cytoscape (14). Although they are not based on an explicit evolutionary model, initial validation studies show that similarity networks correlate well with results from phylogenetic trees (15).
Affiliation: From the Departments of Bioengineering and Therapeutic Sciences and.