Biologists are now challenged with the functional interpretation of vast amounts of sequencing data derived from genomics initiatives. Among all known proteins, the function of enzymes is probably the most investigated and best described at the molecular level. Together with enzymes changing the redox state of substrates and transferring chemical groups between molecules, isomerases catalyze interconversion of isomers, molecules sharing the same atomic composition but different arrangements of chemical groups. This study presents a way of describing isomerases that will give biochemists a method to search and utilize reaction data in a more knowledge-based manner. It captures our current knowledge, characterizing the chemistry of isomerization in biology, and will contribute to improving the annotation of sequences derived from genomes.

Abstract

Isomerization reactions are fundamental in biology, and isomers usually differ in their biological role and pharmacological effects. In this study, we have cataloged the isomerization reactions known to occur in biology using a combination of manual and computational approaches. This method provides a robust basis for comparison and clustering of the reactions into classes. Comparing our results with the Enzyme Commission (EC) classification, the standard approach to represent enzyme function on the basis of the overall chemistry of the catalyzed reaction, expands our understanding of the biochemistry of isomerization. The grouping of reactions involving stereoisomerism is straightforward with two distinct types (racemases/epimerases and cis-trans isomerases), but reactions entailing structural isomerism are diverse and challenging to classify using a hierarchical approach. This study provides an overview of which isomerases occur in nature, how we should describe and classify them, and their diversity.