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Literature summary for 1.1.1.22 extracted from
- UDP-glucose dehydrogenase activity and optimal downstream cellular function require dynamic reorganization at the dimer-dimer subunit interfaces (2013), J. Biol. Chem., 288, 35049-35057.
Application
| Application | Comment | Organism |
|---|---|---|
| medicine | manipulation of UGDH activity by hexamer stabilization may offer therapeutic options in cancer and other pathologies | Homo sapiens |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| recombinant expression of N-terminally His6-tagged wild-type and mutant enzymes in Escherichia coli strain Rosetta2(DE3)pLysS, recombinant expression in HEK293 cells | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| E110A | site-directed mutagenesis, the mutant, although dimeric in the apo form, exhibits only about 50% reduction in Vmax, but is highly unstable in solution and in cultured cells so it cannot be evaluated unambiguously | Homo sapiens |
| additional information | UDP-glucose dehydrogenase mutants are engineered to perturb hexamer:dimer quaternary structure equilibrium. Dimeric species of UGDH have reduced activity in vitro and in supporting hyaluronan production by cultured cells. The purified enzymes reveal a significant decrease in the enzymatic activity of the obligate dimer and hexamer mutants. The activity of the truncated DELTA132 mutant is negligible. The half-life of UGDH catalytic activity in vitro is reduced by mutations at the dimer interface | Homo sapiens |
| T325A | site-directed mutagenesis, the mutant occurs as dimeric species that can be induced to form hexamers in the ternary complex with substrate and cofactor. The inducible hexamer shows that upon increasing enzyme concentration, which favors the hexameric species, activity is modestly decreased and exhibits cooperativity. The T325A mutant is significantly less efficient in promoting downstream hyaluronan production by HEK293 cells than the wild-type. The activity of the T325A mutant is the most labile, with a half-life of only 24 h that is not extended significantly by substrate and cofactor addition | Homo sapiens |
| T325D | site-directed mutagenesis, the mutant yields exclusively dimeric species. The T325D mutant is significantly less efficient in promoting downstream hyaluronan production by HEK293 cells than the wild-type. UGDH T325D retains its activity similarly to the wild-type enzyme but does not exhibit increased stability in the abortive ternary complex | Homo sapiens |
General Stability
| General Stability | Organism |
|---|---|
| the half-life of UGDH catalytic activity in vitro is reduced by mutations at the dimer interface | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| UDP-xylose | a potent UGDH inhibitor | Homo sapiens |  |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | Michaelis-Menten kinetic, cooperative kinetic behavior occurs in the hexameric enzyme | Homo sapiens | |
| 0.015 | - |
UDP-alpha-D-glucose | pH 7.4, 37°C, recombinant His-tagged mutant T325D | Homo sapiens | |
| 0.034 | - |
UDP-alpha-D-glucose | pH 7.4, 37°C, recombinant His-tagged wild-type enzyme | Homo sapiens | |
| 0.048 | - |
UDP-alpha-D-glucose | pH 7.4, 37°C, recombinant His-tagged mutant T325A | Homo sapiens | |
| 0.646 | - |
NAD+ | pH 7.4, 37°C, recombinant His-tagged wild-type enzyme | Homo sapiens | |
| 0.897 | - |
NAD+ | pH 7.4, 37°C, recombinant His-tagged mutant T325A | Homo sapiens | |
| 1.084 | - |
NAD+ | pH 7.4, 37°C, recombinant His-tagged mutant T325D | Homo sapiens | |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 57000 | - |
x * 57000, recombinant enzyme, SDS-PAGE | Homo sapiens |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | Homo sapiens | the transient capacity to dissociate and reorganize the hydrogen bond network at the interface between dimeric units is an important element of the normal catalytic cycle | ? | - |
? | |
| UDP-alpha-D-glucose + 2 NAD+ + H2O | Homo sapiens | - |
UDP-alpha-D-glucuronate + 2 NADH + 2 H+ | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | O60701 | - |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant N-terminally His6-tagged wild-type and mutant enzymes from Escherichia coli strain Rosetta2(DE3)pLysS by nickel affinity chromatography and dialysis | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| cell culture | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | the transient capacity to dissociate and reorganize the hydrogen bond network at the interface between dimeric units is an important element of the normal catalytic cycle | Homo sapiens | ? | - |
? | |
| UDP-alpha-D-glucose + 2 NAD+ + H2O | - |
Homo sapiens | UDP-alpha-D-glucuronate + 2 NADH + 2 H+ | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| dimer or hexamer | x * 57000, recombinant enzyme, SDS-PAGE | Homo sapiens |
| More | examination of the dimer-dimer subunit interface reveals an extensive network of charge interactions and hydrogen bonding that coordinately stabilize the hexamer in the presence and absence of its cofactor or substrate, involving residue T325. The wild-type UGDH enzyme purifies in a hexamer-dimer equilibrium and transiently undergoes dynamic motion that exposes the dimer-dimer interface during catalysis. Only dynamic UGDH hexamers support robust cellular function, mutant dimeric species of UGDH have reduced activity in vitro and in supporting hyaluronan production by cultured cells. Molecular interactions at the subunit interface, overview. In the apo form Thr325 directly forms a hydrogen bond with Asp105 of the opposite subunit | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| UDP-glucose dehydrogenase | - |
Homo sapiens |
| UGDH | - |
Homo sapiens |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 37 | - |
assay at | Homo sapiens |
Temperature Stability [°C]
| Temperature Stability Minimum [°C] | Temperature Stability Maximum [°C] | Comment | Organism |
|---|---|---|---|
| additional information | - |
thermal stabilities of wild-type and mutant enzymes, overview | Homo sapiens |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.4 | - |
assay at | Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| NAD+ | - |
Homo sapiens | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | mutant dimeric species of UGDH have reduced activity in vitro and in supporting hyaluronan production by cultured cells. The purified enzymes reveal a significant decrease in the enzymatic activity of the obligate dimer and hexamer mutants. Both T325A and T325D mutants were significantly less efficient in promoting downstream hyaluronan production by HEK293 cells | Homo sapiens |
| physiological function | UDP-glucose dehydrogenase activity and optimal downstream cellular function require dynamic reorganization at the dimer-dimer subunit interfaces | Homo sapiens |
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