EC Number   |
General Information |
Reference |
|---|
   5.1.3.7 | evolution |
Gne epimerases, excluding enzymes active on UDP-N-acetylgalactosaminuronic acid and undecaprenyl diphosphate-N-acetylgalactosamine, named GnaB or Gnu, are in the same clade as the GalE 4-epimerases for interconversion of UDP-glucose and UDP-galactose, phylogenetic analysis, overview |
-, 728616 |
| 5.1.3.7 | evolution |
KfoA shows a high degree of identity with members of GalE group 2 |
-, 746866 |
| 5.1.3.7 | evolution |
UDP-Gal 4-epimerases and the other GalE-like UDP-sugar 4-epimerases belong to the short-chain dehydrogenase/reductase (SDR) superfamily of proteins. Classification of UDP-hexose 4-epimerases into three groups with distinct substrate promiscuity. Group 1 contains the 4-epimerases that exhibit a strong preference for non-acetylated substrates (such as Escherichia coli enzyme eGalE), group 2 members can epimerize both non-acetylated and N-acetylated substrates equally well (such as the human enzyme hGalE), and group 3 epimerases are very specific for N-acetylated substrates (like the WbpP from Pseudomonas aeruginosa). The enzyme from Pleisomonas shigelloides is a group 3 epimerase. The model of the '297-308 belt' is proposed to determine substrate specificity in group 3 members. The belts conformation supports (i) the formation of a hydrophobic cluster that interacts with the methyl group of the N-acetyl moiety, (ii) a correct positioning of the Asn195, and (iii) orients the substrate so the GlcNAc moiety will form hydrogen bonds with Ser143 and Ser144. Due to this belt and the resulting hydrogen bond network, the group 3 members have a distinct conformation at this region whereas the conformation of group 1 and group 2 enzymes is very similar |
747460 |
| 5.1.3.7 | evolution |
UDP-Gal 4-epimerases and the other GalE-like UDP-sugar 4-epimerases belong to the short-chain dehydrogenase/reductase (SDR) superfamily of proteins. Classification of UDP-hexose 4-epimerases into three groups with distinct substrate promiscuity. Group 1 contains the 4-epimerases that exhibit a strong preference for non-acetylated substrates (such as Escherichia coli enzyme eGalE), group 2 members can epimerize both non-acetylated and N-acetylated substrates equally well (such as the human enzyme hGalE), and group 3 epimerases are very specific for N-acetylated substrates (like the WbpP from Pseudomonas aeruginosa). The model of the '297-308 belt' is proposed to determine substrate specificity in group 3 members. The belts conformation supports (i) the formation of a hydrophobic cluster that interacts with the methyl group of the N-acetyl moiety, (ii) a correct positioning of the Asn195, and (iii) orients the substrate so the GlcNAc moiety will form hydrogen bonds with Ser143 and Ser144. Due to this belt and the resulting hydrogen bond network, the group 3 members have a distinct conformation at this region whereas the conformation of group 1 and group 2 enzymes is very similar |
747460 |
| 5.1.3.7 | evolution |
UDP-hexose 4-epimerases belong to the superfamily of short-chain dehydrogenase/reductase group 2, which typically show a two-domain structure |
726782 |
| 5.1.3.7 | evolution |
UDP-hexose 4-epimerases belong to the superfamily of short-chain dehydrogenase/reductase group 3 |
726860 |
| 5.1.3.7 | evolution |
UDP-hexose 4-epimerases belong to the superfamily of short-chain/reductase having two-domain structure. The N-terminal domain with conserved sequence GxxGxxG forms a modified Rossmann-fold and is involved in binding of the cofactor NAD+, whereas a smaller domain with conserved sequence YxxxK is involved in substrate binding. Both functional motifs conserved in the SDR superfamily members are identified in GalESp1 and GalESp2. Based on its substrate specificity, GalEs can be divided into three groups. Group 1 epimerases strongly prefer non-acetylated substrates (UDP-Glc/Gal), with a corresponding Y300 residue. Group 2 epimerases can epimerize both acetylated (UDP-GlcNAc/GalNAc) and non-acetylated substrates. Group 3 epimerases show a strong preference for acetylated substrates with a corresponding G86 residue. GalESp2 is a group 2 enzyme, GalE enzymes belonging to group 2 contain KSYNNC |
-, 747049 |
| 5.1.3.7 | malfunction |
silencing GALE gene with specific siRNAs results in a markedly inhibition of proteoglycans (PGs)synthesis in human articular chondrocytes. GALE protein levels are also decreased in both human osteoarthritis cartilage, thus leading to losses of PGs contents. GALE inhibition might contribute to osteoarthritis progress. Mutations of gene GALE in humans results in an inherited metabolic disease, the type III galactosemia |
746966 |
| 5.1.3.7 | malfunction |
the S306Y mutation allows a switch from group 2 to group 1 and forms steric clashes between the group 3 epimerases and their substrates, which results in the observed loss of activity |
747460 |
| 5.1.3.7 | malfunction |
the S306Y mutation allows a switch from group 2 to group 1 and forms steric clashes between the group 3 epimerases and their substrates,which results in the observed loss of activity |
747460 |
