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Literature summary for 5.1.3.2 extracted from
- UDP-hexose 4-epimerases a view on structure, mechanism and substrate specificity (2015), Carbohydr. Res., 414, 8-14 .
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| S124A | site-directed mutagenesis | Escherichia coli |
| S124A/Y229F | site-directed mutagenesis, inactive mutant | Escherichia coli |
| 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 |
| S144K | site-directed mutagenesis, inactive mutant | Escherichia coli |
| 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 |
| 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 |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| UDP-alpha-D-glucose | Homo sapiens | - |
UDP-alpha-D-galactose | - |
r |  |
| UDP-alpha-D-glucose | Escherichia coli | - |
UDP-alpha-D-galactose | - |
r | |
| UDP-alpha-D-glucose | Drosophila melanogaster | - |
UDP-alpha-D-galactose | - |
r | |
| UDP-alpha-D-glucose | Streptococcus thermophilus | - |
UDP-alpha-D-galactose | - |
r | |
| UDP-alpha-D-glucose | Marinithermus hydrothermalis | - |
UDP-alpha-D-galactose | - |
r | |
| UDP-alpha-D-glucose | Marinithermus hydrothermalis DSM 14884 / JCM 11576 / T1 | - |
UDP-alpha-D-galactose | - |
r | |
| UDP-glucose | Saccharomyces cerevisiae | - |
UDP-galactose | - |
r | |
| UDP-glucose | Thermus thermophilus | - |
UDP-galactose | - |
r | |
| UDP-glucose | Saccharomyces cerevisiae ATCC 204508 / S288c | - |
UDP-galactose | - |
r | |
| UDP-glucose | Thermus thermophilus SG0.5JP17-16 | - |
UDP-galactose | - |
r | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Drosophila melanogaster | Q9W0P5 | - |
- |
| Escherichia coli | P09147 | - |
- |
| Homo sapiens | Q14376 | - |
- |
| Marinithermus hydrothermalis | F2NQX6 | - |
- |
| Marinithermus hydrothermalis DSM 14884 / JCM 11576 / T1 | F2NQX6 | - |
- |
| Saccharomyces cerevisiae | P04397 | - |
- |
| Saccharomyces cerevisiae ATCC 204508 / S288c | P04397 | - |
- |
| Streptococcus thermophilus | P21977 | - |
- |
| Thermus thermophilus | F6DEY6 | - |
- |
| Thermus thermophilus SG0.5JP17-16 | F6DEY6 | - |
- |
Reaction
| Reaction | Comment | Organism | Reaction ID |
|---|---|---|---|
| UDP-alpha-D-glucose = UDP-alpha-D-galactose | reaction mechanism, overview | Homo sapiens | |
| UDP-alpha-D-glucose = UDP-alpha-D-galactose | reaction mechanism, overview | Drosophila melanogaster | |
| UDP-alpha-D-glucose = UDP-alpha-D-galactose | reaction mechanism, overview | Streptococcus thermophilus | |
| UDP-alpha-D-glucose = UDP-alpha-D-galactose | reaction mechanism, overview | Saccharomyces cerevisiae | |
| UDP-alpha-D-glucose = UDP-alpha-D-galactose | reaction mechanism, overview | Thermus thermophilus | |
| UDP-alpha-D-glucose = UDP-alpha-D-galactose | reaction mechanism, overview | Marinithermus hydrothermalis | |
| 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)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 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 | ? | - |
? | |
| additional information | the bifunctional enzyme GAL10 also exhibits galactose mutarotase activity, EC 5.1.3.3 | Saccharomyces cerevisiae | ? | - |
? | |
| additional information | the bifunctional enzyme GAL10 also exhibits galactose mutarotase activity, EC 5.1.3.3 | Saccharomyces cerevisiae ATCC 204508 / S288c | ? | - |
? | |
| UDP-alpha-D-glucose | - |
Homo sapiens | UDP-alpha-D-galactose | - |
r | |
| UDP-alpha-D-glucose | - |
Escherichia coli | UDP-alpha-D-galactose | - |
r | |
| UDP-alpha-D-glucose | - |
Drosophila melanogaster | UDP-alpha-D-galactose | - |
r | |
| UDP-alpha-D-glucose | - |
Streptococcus thermophilus | UDP-alpha-D-galactose | - |
r | |
| UDP-alpha-D-glucose | - |
Marinithermus hydrothermalis | UDP-alpha-D-galactose | - |
r | |
| UDP-alpha-D-glucose | - |
Marinithermus hydrothermalis DSM 14884 / JCM 11576 / T1 | UDP-alpha-D-galactose | - |
r | |
| UDP-glucose | - |
Saccharomyces cerevisiae | UDP-galactose | - |
r | |
| UDP-glucose | - |
Thermus thermophilus | UDP-galactose | - |
r | |
| UDP-glucose | - |
Saccharomyces cerevisiae ATCC 204508 / S288c | UDP-galactose | - |
r | |
| UDP-glucose | - |
Thermus thermophilus SG0.5JP17-16 | UDP-galactose | - |
r | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| 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 |
| 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
| Synonyms | Comment | Organism |
|---|---|---|
| GAL10 | - |
Saccharomyces cerevisiae |
| Galactowaldenase | - |
Saccharomyces cerevisiae |
| GalE | - |
Homo sapiens |
| GalE | - |
Escherichia coli |
| GalE | - |
Drosophila melanogaster |
| GalE | - |
Streptococcus thermophilus |
| GalE | - |
Thermus thermophilus |
| GalE | - |
Marinithermus hydrothermalis |
| UDP-Gal 4-epimerase | - |
Homo sapiens |
| UDP-Gal 4-epimerase | - |
Escherichia coli |
| UDP-Gal 4-epimerase | - |
Drosophila melanogaster |
| UDP-Gal 4-epimerase | - |
Streptococcus thermophilus |
| UDP-Gal 4-epimerase | - |
Saccharomyces cerevisiae |
| UDP-Gal 4-epimerase | - |
Thermus thermophilus |
| UDP-Gal 4-epimerase | - |
Marinithermus hydrothermalis |
| UDP-hexose 4-epimerase | - |
Homo sapiens |
| UDP-hexose 4-epimerase | - |
Escherichia coli |
| UDP-hexose 4-epimerase | - |
Drosophila melanogaster |
| UDP-hexose 4-epimerase | - |
Streptococcus thermophilus |
| UDP-hexose 4-epimerase | - |
Saccharomyces cerevisiae |
| UDP-hexose 4-epimerase | - |
Thermus thermophilus |
| UDP-hexose 4-epimerase | - |
Marinithermus hydrothermalis |
| UDP-sugar 4-epimerase | - |
Homo sapiens |
| UDP-sugar 4-epimerase | - |
Escherichia coli |
| UDP-sugar 4-epimerase | - |
Drosophila melanogaster |
| UDP-sugar 4-epimerase | - |
Streptococcus thermophilus |
| UDP-sugar 4-epimerase | - |
Saccharomyces cerevisiae |
| UDP-sugar 4-epimerase | - |
Thermus thermophilus |
| UDP-sugar 4-epimerase | - |
Marinithermus hydrothermalis |
| Uridine diphosphate galactose 4-epimerase | - |
Homo sapiens |
| Uridine diphosphate galactose 4-epimerase | - |
Escherichia coli |
| Uridine diphosphate galactose 4-epimerase | - |
Drosophila melanogaster |
| Uridine diphosphate galactose 4-epimerase | - |
Streptococcus thermophilus |
| Uridine diphosphate galactose 4-epimerase | - |
Saccharomyces cerevisiae |
| Uridine diphosphate galactose 4-epimerase | - |
Thermus thermophilus |
| Uridine diphosphate galactose 4-epimerase | - |
Marinithermus hydrothermalis |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| 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 | |
| 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 | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| metabolism | UDP-sugar 4-epimerase (GalE) is one of enzymes in the Leloir pathway | Homo sapiens |
| metabolism | UDP-sugar 4-epimerase (GalE) is one of enzymes in the Leloir pathway | Escherichia coli |
| metabolism | UDP-sugar 4-epimerase (GalE) is one of enzymes in the Leloir pathway | Drosophila melanogaster |
| metabolism | UDP-sugar 4-epimerase (GalE) is one of enzymes in the Leloir pathway | Streptococcus thermophilus |
| metabolism | UDP-sugar 4-epimerase (GalE) is one of enzymes in the Leloir pathway | Saccharomyces cerevisiae |
| metabolism | UDP-sugar 4-epimerase (GalE) is one of enzymes in the Leloir pathway | Thermus thermophilus |
| metabolism | UDP-sugar 4-epimerase (GalE) is one of enzymes in the Leloir pathway | Marinithermus hydrothermalis |
| additional information | comparison of the hexagonal box model of sugar-binding pockeets of several GalE enzymes | Thermus thermophilus |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| physiological function | UDP-galactose 4-epimerase is important for the biosynthesis of polysaccharide structures | Saccharomyces cerevisiae |
| physiological function | UDP-galactose 4-epimerase is important for the biosynthesis of polysaccharide structures | Thermus thermophilus |
| physiological function | UDP-galactose 4-epimerase is important for the biosynthesis of polysaccharide structures | Marinithermus hydrothermalis |
| physiological function | UDP-galactose 4-epimerase is important for the biosynthesis of polysaccharide structures, such as capsular polysaccharide (CPS) | Escherichia coli |
| 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 |
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