Any feedback?
Literature summary for 5.1.3.7 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 |
|---|---|---|
| A209H | site-directed mutagenesis, the mutation results in limited ability to epimerize acetylated residues | Pseudomonas aeruginosa |
| A209N | site-directed mutagenesis, the mutation enhances the specificity for acetylated substrates accompanied by a lower catalytic efficiency | Pseudomonas aeruginosa |
| G102K | site-directed mutagenesis, the mutation slightly reduces activity on acetylated substrates and almost abolishes activity on non-acetylated substrates | Pseudomonas aeruginosa |
| 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 |
| Q201E | site-directed mutagenesis, the mutation slightly reduces activity on acetylated substrates and almost abolishes activity on non-acetylated substrates | Pseudomonas aeruginosa |
| 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 |
| 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)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| UDP-N-acetyl-alpha-D-glucosamine | Plesiomonas shigelloides | - |
UDP-N-acetyl-alpha-D-galactosamine | - |
r |  |
| UDP-N-acetyl-alpha-D-glucosamine | Pseudomonas aeruginosa | - |
UDP-N-acetyl-alpha-D-galactosamine | - |
r | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Plesiomonas shigelloides | Q7BJX9 | - |
- |
| Pseudomonas aeruginosa | Q8KN66 | - |
- |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | the group 3 epimerase WbpP from Pseudomonas aeruginosa is very specific for N-acetylated substrates | Pseudomonas aeruginosa | ? | - |
? | |
| UDP-N-acetyl-alpha-D-glucosamine | - |
Plesiomonas shigelloides | UDP-N-acetyl-alpha-D-galactosamine | - |
r | |
| UDP-N-acetyl-alpha-D-glucosamine | - |
Pseudomonas aeruginosa | UDP-N-acetyl-alpha-D-galactosamine | - |
r | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| group 3 epimerase | - |
Plesiomonas shigelloides |
| group 3 epimerase | - |
Pseudomonas aeruginosa |
| UDP-GlcNAc 4-epimerase | - |
Pseudomonas aeruginosa |
| UDP-hexose 4-epimerase | - |
Plesiomonas shigelloides |
| UDP-hexose 4-epimerase | - |
Pseudomonas aeruginosa |
| UDP-sugar 4-epimerase | - |
Plesiomonas shigelloides |
| UDP-sugar 4-epimerase | - |
Pseudomonas aeruginosa |
| UDPGlcNAc 4-epimerase | - |
Plesiomonas shigelloides |
| WbgU | - |
Plesiomonas shigelloides |
| WbPP | - |
Pseudomonas aeruginosa |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| NAD+ | - |
Plesiomonas shigelloides | |
| NAD+ | - |
Pseudomonas aeruginosa | |
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). 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
