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Literature summary extracted from
- UDP-hexose 4-epimerases a view on structure, mechanism and substrate specificity (2015), Carbohydr. Res., 414, 8-14 .
Protein Variants
| EC Number | Protein Variants | Comment | Organism |
|---|---|---|---|
| 5.1.3.2 | S124A | site-directed mutagenesis | Escherichia coli |
| 5.1.3.2 | S124A/Y229F | site-directed mutagenesis, inactive mutant | Escherichia coli |
| 5.1.3.2 | S143A | site-directed mutagenesis, the mutation abolishes activity on non-acetylated substrates, probably due to loss of the hydrogen bonding, whereas the mutant remains active on UDP-GlcNAc/UDP-GalNAc, as additional stabilizing interactions with the N-acetyl moiety are present | Escherichia coli |
| 5.1.3.2 | S144K | site-directed mutagenesis, inactive mutant | Escherichia coli |
| 5.1.3.2 | S306Y | site-directed mutagenesis, the 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 | Escherichia coli |
| 5.1.3.2 | Y299C | site-directed mutagenesis, structure analysis in complex with UDP-N-acetylglucosamine, PDB ID 1LRK, the Y299C mutation in eGalE results in significant loss of activity on non-acetylated substrates | Escherichia coli |
| 5.1.3.7 | A209H | site-directed mutagenesis, the mutation results in limited ability to epimerize acetylated residues | Pseudomonas aeruginosa |
| 5.1.3.7 | A209N | site-directed mutagenesis, the mutation enhances the specificity for acetylated substrates accompanied by a lower catalytic efficiency | Pseudomonas aeruginosa |
| 5.1.3.7 | G102K | site-directed mutagenesis, the mutation slightly reduces activity on acetylated substrates and almost abolishes activity on non-acetylated substrates | Pseudomonas aeruginosa |
| 5.1.3.7 | G102K/Q201E | site-directed mutagenesis, as a result of the introduction of both mutations at the same time, a salt bridge is formed, which results in a rescue of the activity for acetylated substrates, probably due to restoration of the slight distortion that is observed in both single mutants | Pseudomonas aeruginosa |
| 5.1.3.7 | Q201E | site-directed mutagenesis, the mutation slightly reduces activity on acetylated substrates and almost abolishes activity on non-acetylated substrates | Pseudomonas aeruginosa |
| 5.1.3.7 | S306Y | site-directed mutagenesis, the 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 | Plesiomonas shigelloides |
| 5.1.3.7 | S306Y | site-directed mutagenesis, the 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. The S306Y mutation in WbpP totally abolishes the activity of the enzyme | Pseudomonas aeruginosa |
Natural Substrates/ Products (Substrates)
| EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 5.1.3.2 | UDP-alpha-D-glucose | Homo sapiens | - |
UDP-alpha-D-galactose | - |
r |  |
| 5.1.3.2 | UDP-alpha-D-glucose | Escherichia coli | - |
UDP-alpha-D-galactose | - |
r | |
| 5.1.3.2 | UDP-alpha-D-glucose | Drosophila melanogaster | - |
UDP-alpha-D-galactose | - |
r | |
| 5.1.3.2 | UDP-alpha-D-glucose | Streptococcus thermophilus | - |
UDP-alpha-D-galactose | - |
r | |
| 5.1.3.2 | UDP-alpha-D-glucose | Marinithermus hydrothermalis | - |
UDP-alpha-D-galactose | - |
r | |
| 5.1.3.2 | UDP-alpha-D-glucose | Marinithermus hydrothermalis DSM 14884 / JCM 11576 / T1 | - |
UDP-alpha-D-galactose | - |
r | |
| 5.1.3.2 | UDP-glucose | Saccharomyces cerevisiae | - |
UDP-galactose | - |
r | |
| 5.1.3.2 | UDP-glucose | Thermus thermophilus | - |
UDP-galactose | - |
r | |
| 5.1.3.2 | UDP-glucose | Saccharomyces cerevisiae ATCC 204508 / S288c | - |
UDP-galactose | - |
r | |
| 5.1.3.2 | UDP-glucose | Thermus thermophilus SG0.5JP17-16 | - |
UDP-galactose | - |
r | |
| 5.1.3.7 | UDP-N-acetyl-alpha-D-glucosamine | Plesiomonas shigelloides | - |
UDP-N-acetyl-alpha-D-galactosamine | - |
r | |
| 5.1.3.7 | UDP-N-acetyl-alpha-D-glucosamine | Pseudomonas aeruginosa | - |
UDP-N-acetyl-alpha-D-galactosamine | - |
r | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 5.1.3.2 | Drosophila melanogaster | Q9W0P5 | - |
- |
| 5.1.3.2 | Escherichia coli | P09147 | - |
- |
| 5.1.3.2 | Homo sapiens | Q14376 | - |
- |
| 5.1.3.2 | Marinithermus hydrothermalis | F2NQX6 | - |
- |
| 5.1.3.2 | Marinithermus hydrothermalis DSM 14884 / JCM 11576 / T1 | F2NQX6 | - |
- |
| 5.1.3.2 | Saccharomyces cerevisiae | P04397 | - |
- |
| 5.1.3.2 | Saccharomyces cerevisiae ATCC 204508 / S288c | P04397 | - |
- |
| 5.1.3.2 | Streptococcus thermophilus | P21977 | - |
- |
| 5.1.3.2 | Thermus thermophilus | F6DEY6 | - |
- |
| 5.1.3.2 | Thermus thermophilus SG0.5JP17-16 | F6DEY6 | - |
- |
| 5.1.3.7 | Plesiomonas shigelloides | Q7BJX9 | - |
- |
| 5.1.3.7 | Pseudomonas aeruginosa | Q8KN66 | - |
- |
Reaction
| EC Number | Reaction | Comment | Organism | Reaction ID |
|---|---|---|---|---|
| 5.1.3.2 | UDP-alpha-D-glucose = UDP-alpha-D-galactose | reaction mechanism, overview | Homo sapiens | |
| 5.1.3.2 | UDP-alpha-D-glucose = UDP-alpha-D-galactose | reaction mechanism, overview | Drosophila melanogaster | |
| 5.1.3.2 | UDP-alpha-D-glucose = UDP-alpha-D-galactose | reaction mechanism, overview | Streptococcus thermophilus | |
| 5.1.3.2 | UDP-alpha-D-glucose = UDP-alpha-D-galactose | reaction mechanism, overview | Saccharomyces cerevisiae | |
| 5.1.3.2 | UDP-alpha-D-glucose = UDP-alpha-D-galactose | reaction mechanism, overview | Thermus thermophilus | |
| 5.1.3.2 | UDP-alpha-D-glucose = UDP-alpha-D-galactose | reaction mechanism, overview | Marinithermus hydrothermalis | |
| 5.1.3.2 | UDP-alpha-D-glucose = UDP-alpha-D-galactose | revolving door reaction mechanism, Tyr149 is the base catalyst for hydride transfer, overview. The enzyme undergoes a conformational change upon binding of the UDP sugar, which is in fact a result of the binding of the UMP-moiety of the substrate. The conserved lysine from the YxxxK motif plays an important role in the activation of the cofactor, as due to the conformational change, the 6-ammonium group is hydrogen-bonded to both the 2'- and 3'-hydroxylgroups of the nicotinamide riboside of NAD+ | Escherichia coli |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 5.1.3.2 | additional information | Escherichia coli GalE is unable to catalyse the epimerization of acetylated substrates due to the so-called gatekeeper wall of the active site substrate-binding hexagonal box that is occupied by a bulky residue, Tyr299 | Escherichia coli | ? | - |
? | |
| 5.1.3.2 | additional information | the bifunctional enzyme GAL10 also exhibits galactose mutarotase activity, EC 5.1.3.3 | Saccharomyces cerevisiae | ? | - |
? | |
| 5.1.3.2 | additional information | the bifunctional enzyme GAL10 also exhibits galactose mutarotase activity, EC 5.1.3.3 | Saccharomyces cerevisiae ATCC 204508 / S288c | ? | - |
? | |
| 5.1.3.2 | UDP-alpha-D-glucose | - |
Homo sapiens | UDP-alpha-D-galactose | - |
r | |
| 5.1.3.2 | UDP-alpha-D-glucose | - |
Escherichia coli | UDP-alpha-D-galactose | - |
r | |
| 5.1.3.2 | UDP-alpha-D-glucose | - |
Drosophila melanogaster | UDP-alpha-D-galactose | - |
r | |
| 5.1.3.2 | UDP-alpha-D-glucose | - |
Streptococcus thermophilus | UDP-alpha-D-galactose | - |
r | |
| 5.1.3.2 | UDP-alpha-D-glucose | - |
Marinithermus hydrothermalis | UDP-alpha-D-galactose | - |
r | |
| 5.1.3.2 | UDP-alpha-D-glucose | - |
Marinithermus hydrothermalis DSM 14884 / JCM 11576 / T1 | UDP-alpha-D-galactose | - |
r | |
| 5.1.3.2 | UDP-glucose | - |
Saccharomyces cerevisiae | UDP-galactose | - |
r | |
| 5.1.3.2 | UDP-glucose | - |
Thermus thermophilus | UDP-galactose | - |
r | |
| 5.1.3.2 | UDP-glucose | - |
Saccharomyces cerevisiae ATCC 204508 / S288c | UDP-galactose | - |
r | |
| 5.1.3.2 | UDP-glucose | - |
Thermus thermophilus SG0.5JP17-16 | UDP-galactose | - |
r | |
| 5.1.3.7 | additional information | the group 3 epimerase WbpP from Pseudomonas aeruginosa is very specific for N-acetylated substrates | Pseudomonas aeruginosa | ? | - |
? | |
| 5.1.3.7 | UDP-N-acetyl-alpha-D-glucosamine | - |
Plesiomonas shigelloides | UDP-N-acetyl-alpha-D-galactosamine | - |
r | |
| 5.1.3.7 | UDP-N-acetyl-alpha-D-glucosamine | - |
Pseudomonas aeruginosa | UDP-N-acetyl-alpha-D-galactosamine | - |
r | |
Subunits
| EC Number | Subunits | Comment | Organism |
|---|---|---|---|
| 5.1.3.2 | More | determination of the structure of human UDP-Gal 4-epimerase. The C-terminal domain is built from five beta-strands and four alpha-helices | Homo sapiens |
| 5.1.3.2 | More | the enzyme has an N-terminal nucleotide binding domain and a smaller C-terminal domain that is responsible for the correct positioning of its substrate, a UDP-sugar. The N-terminal domain comprises seven parallel beta-strands that are flanked on both sides by alpha-helices and shape the Rossmann fold. Two paired Rossmann folds tightly bind one NAD+ cofactor per subunit | Escherichia coli |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 5.1.3.2 | GAL10 | - |
Saccharomyces cerevisiae |
| 5.1.3.2 | Galactowaldenase | - |
Saccharomyces cerevisiae |
| 5.1.3.2 | GalE | - |
Homo sapiens |
| 5.1.3.2 | GalE | - |
Escherichia coli |
| 5.1.3.2 | GalE | - |
Drosophila melanogaster |
| 5.1.3.2 | GalE | - |
Streptococcus thermophilus |
| 5.1.3.2 | GalE | - |
Thermus thermophilus |
| 5.1.3.2 | GalE | - |
Marinithermus hydrothermalis |
| 5.1.3.2 | UDP-Gal 4-epimerase | - |
Homo sapiens |
| 5.1.3.2 | UDP-Gal 4-epimerase | - |
Escherichia coli |
| 5.1.3.2 | UDP-Gal 4-epimerase | - |
Drosophila melanogaster |
| 5.1.3.2 | UDP-Gal 4-epimerase | - |
Streptococcus thermophilus |
| 5.1.3.2 | UDP-Gal 4-epimerase | - |
Saccharomyces cerevisiae |
| 5.1.3.2 | UDP-Gal 4-epimerase | - |
Thermus thermophilus |
| 5.1.3.2 | UDP-Gal 4-epimerase | - |
Marinithermus hydrothermalis |
| 5.1.3.2 | UDP-hexose 4-epimerase | - |
Homo sapiens |
| 5.1.3.2 | UDP-hexose 4-epimerase | - |
Escherichia coli |
| 5.1.3.2 | UDP-hexose 4-epimerase | - |
Drosophila melanogaster |
| 5.1.3.2 | UDP-hexose 4-epimerase | - |
Streptococcus thermophilus |
| 5.1.3.2 | UDP-hexose 4-epimerase | - |
Saccharomyces cerevisiae |
| 5.1.3.2 | UDP-hexose 4-epimerase | - |
Thermus thermophilus |
| 5.1.3.2 | UDP-hexose 4-epimerase | - |
Marinithermus hydrothermalis |
| 5.1.3.2 | UDP-sugar 4-epimerase | - |
Homo sapiens |
| 5.1.3.2 | UDP-sugar 4-epimerase | - |
Escherichia coli |
| 5.1.3.2 | UDP-sugar 4-epimerase | - |
Drosophila melanogaster |
| 5.1.3.2 | UDP-sugar 4-epimerase | - |
Streptococcus thermophilus |
| 5.1.3.2 | UDP-sugar 4-epimerase | - |
Saccharomyces cerevisiae |
| 5.1.3.2 | UDP-sugar 4-epimerase | - |
Thermus thermophilus |
| 5.1.3.2 | UDP-sugar 4-epimerase | - |
Marinithermus hydrothermalis |
| 5.1.3.2 | Uridine diphosphate galactose 4-epimerase | - |
Homo sapiens |
| 5.1.3.2 | Uridine diphosphate galactose 4-epimerase | - |
Escherichia coli |
| 5.1.3.2 | Uridine diphosphate galactose 4-epimerase | - |
Drosophila melanogaster |
| 5.1.3.2 | Uridine diphosphate galactose 4-epimerase | - |
Streptococcus thermophilus |
| 5.1.3.2 | Uridine diphosphate galactose 4-epimerase | - |
Saccharomyces cerevisiae |
| 5.1.3.2 | Uridine diphosphate galactose 4-epimerase | - |
Thermus thermophilus |
| 5.1.3.2 | Uridine diphosphate galactose 4-epimerase | - |
Marinithermus hydrothermalis |
| 5.1.3.7 | group 3 epimerase | - |
Plesiomonas shigelloides |
| 5.1.3.7 | group 3 epimerase | - |
Pseudomonas aeruginosa |
| 5.1.3.7 | UDP-GlcNAc 4-epimerase | - |
Pseudomonas aeruginosa |
| 5.1.3.7 | UDP-hexose 4-epimerase | - |
Plesiomonas shigelloides |
| 5.1.3.7 | UDP-hexose 4-epimerase | - |
Pseudomonas aeruginosa |
| 5.1.3.7 | UDP-sugar 4-epimerase | - |
Plesiomonas shigelloides |
| 5.1.3.7 | UDP-sugar 4-epimerase | - |
Pseudomonas aeruginosa |
| 5.1.3.7 | UDPGlcNAc 4-epimerase | - |
Plesiomonas shigelloides |
| 5.1.3.7 | WbgU | - |
Plesiomonas shigelloides |
| 5.1.3.7 | WbPP | - |
Pseudomonas aeruginosa |
Cofactor
| EC Number | Cofactor | Comment | Organism | Structure |
|---|---|---|---|---|
| 5.1.3.2 | NAD+ | the NAD+ cofactor can be removed from human GalE without denaturation. Fewer protein-NAD+ contacts are observed in the crystal structure, which explains the reversible character of cofactor binding | Homo sapiens | |
| 5.1.3.2 | NAD+ | two paired Rossmann folds tightly bind one NAD+ cofactor per subunit. In Escherichia coli GalE, the NAD+ interacts more extensively with the protein than is observed with other SDR enzymes. pH-Dependent charge transfer complex between Tyr149 and NAD+ | Escherichia coli | |
| 5.1.3.7 | NAD+ | - |
Plesiomonas shigelloides | |
| 5.1.3.7 | NAD+ | - |
Pseudomonas aeruginosa | |
General Information
| EC Number | General Information | Comment | Organism |
|---|---|---|---|
| 5.1.3.2 | 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) | Homo sapiens |
| 5.1.3.2 | 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) | Drosophila melanogaster |
| 5.1.3.2 | 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) | Streptococcus thermophilus |
| 5.1.3.2 | 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) | Saccharomyces cerevisiae |
| 5.1.3.2 | 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) | Thermus thermophilus |
| 5.1.3.2 | 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) | Marinithermus hydrothermalis |
| 5.1.3.2 | 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). Despite the relatively low sequence identity among all three groups, the similarity of the enzymes' tertiary structures is striking with an overall RMSD of the multiple structure alignment being 1.08 A and variation being most pronounced at the C-terminal end | Escherichia coli |
| 5.1.3.2 | malfunction | the replacement of the double glycine motif, observed right next to the conserved serine/threonine (T117) that is part of the hexagonal box, by a single alanine or serine as seen in the other UDP-hexose epimerases results in a strongly reduced specific activity and turnover number | Marinithermus hydrothermalis |
| 5.1.3.2 | 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 | Escherichia coli |
| 5.1.3.2 | metabolism | UDP-sugar 4-epimerase (GalE) is one of enzymes in the Leloir pathway | Homo sapiens |
| 5.1.3.2 | metabolism | UDP-sugar 4-epimerase (GalE) is one of enzymes in the Leloir pathway | Escherichia coli |
| 5.1.3.2 | metabolism | UDP-sugar 4-epimerase (GalE) is one of enzymes in the Leloir pathway | Drosophila melanogaster |
| 5.1.3.2 | metabolism | UDP-sugar 4-epimerase (GalE) is one of enzymes in the Leloir pathway | Streptococcus thermophilus |
| 5.1.3.2 | metabolism | UDP-sugar 4-epimerase (GalE) is one of enzymes in the Leloir pathway | Saccharomyces cerevisiae |
| 5.1.3.2 | metabolism | UDP-sugar 4-epimerase (GalE) is one of enzymes in the Leloir pathway | Thermus thermophilus |
| 5.1.3.2 | metabolism | UDP-sugar 4-epimerase (GalE) is one of enzymes in the Leloir pathway | Marinithermus hydrothermalis |
| 5.1.3.2 | additional information | comparison of the hexagonal box model of sugar-binding pockeets of several GalE enzymes | Thermus thermophilus |
| 5.1.3.2 | additional information | comparison of the hexagonal box model of sugar-binding pockets of several GalE enzymes. A unique double glycine motif is observed right next to the conserved serine/threonine (T117) that is part of the hexagonal box important for substrate specificity | Marinithermus hydrothermalis |
| 5.1.3.2 | additional information | comparison of the hexagonal box model of sugar-binding pockets of several GalE enzymes. The human enzyme has a smaller active site, explaining the secondary role of the human enzyme, which is epimerization of UDP-N-acetylgalactosamine (UDP-Gal-NAc). Activity on the larger acetylated substrates requires a larger active site | Homo sapiens |
| 5.1.3.2 | additional information | enzyme structure and substrate specificity, structure-function relationship, overview. Comparison of the hexagonal box model of sugar-binding pockets of several GalE enzymes | Escherichia coli |
| 5.1.3.2 | physiological function | UDP-galactose 4-epimerase is important for the biosynthesis of other polysaccharide structures, such as capsular polysaccharide (CPS), or extracellular polysaccharide (EPS) from Streptococcus thermophilus, one of the most widely used bacteria in the dairy industry | Streptococcus thermophilus |
| 5.1.3.2 | physiological function | UDP-galactose 4-epimerase is important for the biosynthesis of other polysaccharide structures, such as proteoglycans (PGs) of articular chondrocytes. Secondary role of the human enzyme is epimerization of UDP-N-acetylgalactosamine (UDP-Gal-NAc) | Homo sapiens |
| 5.1.3.2 | physiological function | UDP-galactose 4-epimerase is important for the biosynthesis of polysaccharide structures | Saccharomyces cerevisiae |
| 5.1.3.2 | physiological function | UDP-galactose 4-epimerase is important for the biosynthesis of polysaccharide structures | Thermus thermophilus |
| 5.1.3.2 | physiological function | UDP-galactose 4-epimerase is important for the biosynthesis of polysaccharide structures | Marinithermus hydrothermalis |
| 5.1.3.2 | physiological function | UDP-galactose 4-epimerase is important for the biosynthesis of polysaccharide structures, such as capsular polysaccharide (CPS) | Escherichia coli |
| 5.1.3.2 | physiological function | UDP-galactose 4-epimerase plays an essential role in development and homeostasis of Drosophila that extends beyond the Leloir pathway. UDP-galactose 4-epimerase is important for the biosynthesis of polysaccharide structures | Drosophila melanogaster |
| 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 | Plesiomonas shigelloides |
| 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 | Pseudomonas aeruginosa |
| 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 | Plesiomonas shigelloides |
| 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 | Pseudomonas aeruginosa |
| 5.1.3.7 | additional information | enzyme structure and substrate specificity, comparison of the hexagonal box model of sugar-binding pockeets of several UDP-sugar 4-epimerases. Importance and flexibility of the hydrogen bond network | Plesiomonas shigelloides |
| 5.1.3.7 | additional information | enzyme structure and substrate specificity, structure-function relationship, overview. Comparison of the hexagonal box model of sugar-binding pockeets of several UDP-sugar 4-epimerases. Importance and flexibility of the hydrogen bond network. Structural characterization of WbpP in the presence of both substrates, modeling of the substrate-binding pocket represented as a hexagonal-shaped box with the bottom formed by the nicotinamide ring of the cofactor and an open top to accommodate the ring-flipping movement during catalysis. Three of the six walls of the hexagonal box are formed by highly conserved residues: Ser142, Tyr166 and Asn195 in WbpP. The other three walls (Gly102, Ala209 and Ser306 for WbpP) have been proposed to be key determinants for substrate specificity, overview. The so-called gatekeeper wall is occupied by a bulky residue (Tyr299) in Escherichia coli GalE, which is unable to catalyse the epimerization of acetylated substrates, whereas enzymes with a smaller residue are able to convert acetylated substrates | Pseudomonas aeruginosa |
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Release 2023.1 (January 2023)
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