In a series on “Enzyme Evolution in the Postgenomic Era,” this minireview describes approaches for predicting and assigning functions in the enolase superfamily. The approaches include the computation-based strategy that is the focus of the EFI.
Nature's strategies for evolving catalytic functions can be deciphered from the information contained in the rapidly expanding protein sequence databases. However, the functions of many proteins in the protein sequence and structure databases are either uncertain (too divergent to assign function based on homology) or unknown (no homologs), thereby limiting the utility of the databases. The mechanistically diverse enolase superfamily is a paradigm for understanding the structural bases for evolution of enzymatic function. We describe strategies for assigning functions to members of the enolase superfamily that should be applicable to other superfamilies.
Figure 3. Sequence similarity network for enolase superfamily members (excluding enolase subgroup). The various sequences (nodes) are shown as circles; the lines (edges) connecting the nodes are BLASTP connections with E values ≤10−90. The nodes colored gray have unknown functions; those with other colors have assigned functions.
Figure 4. Reactions catalyzed by enolase superfamily members. The various boxes enclose reactions catalyzed by the seven subgroups that have been recognized. 2-PGA, 2-phosphoglycerate; PEP, phosphoenolpyruvate; MAL, β-methylaspartate ammonia lyase; SHCHC, 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylic acid; OSB, o-succinylbenzoic acid; AE Epim, L-Ala-D/L-Glu epimerase; GalD, D-galactonate dehydratase; GlcD, D-gluconate dehydratase; FucD, L-fuconate dehydratase; TarD, D-tartrate dehydratase; RhamD, L-rhamnonate dehydratase; AraD, D-arabinonate dehydratase; GalrD/TalrD, galactarate dehydratase/L-talarate dehydratase; XylD, D-xylonate dehydratase; GlucD, D-glucarate dehydratase; ManD, D-mannonate dehydratase.
2011 EN Superfamily Publication
Reprinted with permission: the Journal of Biological Chemistry. © 2012 by the American Society for Biochemistry and Molecular Biology.