Molecular evolution and functional divergence of UDP-hexose 4-epimerases

UDP-glucose 4-epimerase (GalE) catalyzes the interconversion of UDP-glucose (UDP-Glc) and UDP-galactose (UDPGal) and/or the interconversion of UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylgalactosamine (UDPGalNAc) in sugar metabolism. GalEs belong to the short-chain dehydrogenase/reductase superfamily, use a conserved ?transient keto intermediate? mechanism and have variable substrate specificity. GalEs have been classified into three groups based on substrate specificity: group 1 prefers UDPGlc/Gal, group 3 prefers UDP-GlcNAc/GalNAc, and group 2 has comparable activities for both types of the substrates. The phylogenetic relationship and structural basis for the specificities of GalEs revealed possible molecular evolution of UDPhexose 4-epimerases in various organisms. Based on the recent advances in studies on GalEs and related enzymes, an updated view of their evolutional diversification is presented.

Automated summary

UDP-glucose 4-epimerase (GalE) plays a crucial role in sugar metabolism by interconverting UDP-glucose and UDP-galactose, or UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine. GalEs are classified into three groups based on substrate specificity, and their phylogenetic relationships and structural basis suggest possible molecular evolution. Recent studies on GalEs and related enzymes provide updated insights into their evolutionary diversification.