EC Number | Protein Variants | Comment | Organism |
---|---|---|---|
3.5.1.108 | C125A | as sensitive to 2,3,4-trihydroxybenzaldehyde O-((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl oxime as the wild-type enzyme | Escherichia coli |
3.5.1.108 | C207A | much less sensitive to 2,3,4-trihydroxybenzaldehyde O-((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl oxime inhibition, suggesting that Cys-207 is necessary to form the E-I complex | Escherichia coli |
3.5.1.108 | C214N | as sensitive to 2,3,4-trihydroxybenzaldehyde O-((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl oxime as the wild-type enzyme | Escherichia coli |
3.5.1.108 | C250A | as sensitive to 2,3,4-trihydroxybenzaldehyde O-((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl oxime as the wild-type enzyme | Escherichia coli |
3.5.1.108 | C63S | as sensitive to 2,3,4-trihydroxybenzaldehyde O-((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl oxime as the wild-type enzyme | Escherichia coli |
3.5.1.108 | C65A | as sensitive to 2,3,4-trihydroxybenzaldehyde O-((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl oxime as the wild-type enzyme | Escherichia coli |
3.5.1.108 | Q202W/G210S | mutant loses the time-dependence of N-((2S,3R)-3-hydroxy-1-(hydroxyamino)-1-oxobutan-2-yl)-4-((4-(morpholinomethyl)phenyl)ethynyl)benzamide inhibition. Still sensitive to inhibition by 2,3,4-trihydroxybenzaldehyde O-((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl oxime in a time-dependent manner | Escherichia coli |
EC Number | Inhibitors | Comment | Organism | Structure |
---|---|---|---|---|
3.5.1.108 | (R)-3-(5,8-dihydronaphthalen-2-yl)-N-hydroxy-2-(naphthalene-2-sulfonamido)propanamide | - |
Escherichia coli | |
3.5.1.108 | (S)-N-(1-(2-(3,4-dimethoxy-5-propylphenyl)-4,5-dihydrooxazol-4-yl)vinyl)hydroxylamine | - |
Escherichia coli | |
3.5.1.108 | 2,3-dihydroxy-benzaldehyde O-[5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl]-oxime | weak inhibitor | Escherichia coli | |
3.5.1.108 | 2,4-dihydroxy-benzaldehyde O-[5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl]-oxime | - |
Escherichia coli | |
3.5.1.108 | 3,4,5-trihydroxy-benzaldehyde O-[5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl]-oxime | weak inhibitor, contains a 5 position hydroxyl and exhibits greatly reduced inhibitory potency | Escherichia coli | |
3.5.1.108 | 3,4-dihydroxy-benzaldehyde O-[5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl]-oxime | 50 microM, 49% inhibition | Rhizobium leguminosarum | |
3.5.1.108 | 5'-O-[(E)-(2,3,4-trihydroxybenzylidene)amino]uridine | 50 microM, 80% inhibition, pH-dependent, two-step, covalent inhibitor. 2,3,4-trihydroxybenzaldehyde O-((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl oxime represents a new class of LpxC inhibitors that exploit the uridine binding site to form a covalent complex. While not antibiotic, it may provide a new scaffold for extension of existing LpxC-inhibiting antibiotics to target the UDP binding pocket | Escherichia coli | |
3.5.1.108 | 5'-O-[(E)-(2,3,4-trihydroxybenzylidene)amino]uridine | 50 microM, 21% inhibition, pH-dependent, two-step, covalent inhibitor. 2,3,4-trihydroxybenzaldehyde O-((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl oxime represents a new class of LpxC inhibitors that exploit the uridine binding site to form a covalent complex. While not antibiotic, it may provide a new scaffold for extension of existing LpxC-inhibiting antibiotics to target the UDP binding pocket | Helicobacter pylori | |
3.5.1.108 | 5'-O-[(E)-(3,4-dihydroxybenzylidene)amino]uridine | 50 microM, 60% inhibition, inhibitor as potent as (E)-2,3,4-trihydroxybenzaldehyde O-((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl oxime | Escherichia coli | |
3.5.1.108 | 5'-O-[(E)-(3,4-dihydroxybenzylidene)amino]uridine | 50 microM, 41% inhibition | Helicobacter pylori | |
3.5.1.108 | additional information | dithiothreitol, glutathione and the C207A mutant prevent the formation of a covalent complex by (E)-2,3,4-trihydroxybenzaldehyde O-((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl oxime; no inhibitory effect by 2,4-dihydroxy-benzaldehyde O-[5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl]-oxime, 3,4-dimethoxy-benzaldehyde O-[5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl]-oxime, and 2,3,4-trimethoxy-benzaldehyde O-[5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl]-oxime | Escherichia coli | |
3.5.1.108 | N-(((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)-2-((Z)-2,3,4-trihydroxybenzylideneaminooxy)acetamide | - |
Escherichia coli | |
3.5.1.108 | N-((2S,3R)-3-hydroxy-1-(hydroxyamino)-1-oxobutan-2-yl)-4-((4-(morpholinomethyl)phenyl)ethynyl)benzamide | - |
Escherichia coli |
EC Number | Organism | UniProt | Comment | Textmining |
---|---|---|---|---|
3.5.1.108 | Escherichia coli | - |
- |
- |
3.5.1.108 | Helicobacter pylori | - |
- |
- |
3.5.1.108 | Rhizobium leguminosarum | - |
- |
- |
EC Number | Purification (Comment) | Organism |
---|---|---|
3.5.1.108 | - |
Escherichia coli |
3.5.1.108 | - |
Helicobacter pylori |
3.5.1.108 | - |
Rhizobium leguminosarum |
EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|---|
3.5.1.108 | UDP-3-O-((R)-3-hydroxymyristoyl)-N-acetylglucosamine + H2O | - |
Escherichia coli | UDP-3-O-((R)-3-hydroxymyristoyl)-D-glucosamine + acetate | - |
? |
EC Number | Synonyms | Comment | Organism |
---|---|---|---|
3.5.1.108 | LpxC | - |
Escherichia coli |
3.5.1.108 | LpxC | - |
Helicobacter pylori |
3.5.1.108 | LpxC | - |
Rhizobium leguminosarum |
3.5.1.108 | UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase | - |
Escherichia coli |
3.5.1.108 | UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase | - |
Helicobacter pylori |
3.5.1.108 | UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase | - |
Rhizobium leguminosarum |
EC Number | Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|---|
3.5.1.108 | 30 | - |
assay at | Escherichia coli |
EC Number | pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|---|
3.5.1.108 | 7.4 | - |
assay at | Escherichia coli |
EC Number | Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|---|
3.5.1.108 | 0.054 | - |
5'-O-[(E)-(2,3,4-trihydroxybenzylidene)amino]uridine | - |
Escherichia coli |
EC Number | IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|---|
3.5.1.108 | additional information | - |
above 500 microM | Escherichia coli | 2,4-dihydroxy-benzaldehyde O-[5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl]-oxime | |
3.5.1.108 | additional information | - |
above 500 microM | Escherichia coli | 2,3-dihydroxy-benzaldehyde O-[5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl]-oxime | |
3.5.1.108 | additional information | - |
above 500 microM | Escherichia coli | 3,4,5-trihydroxy-benzaldehyde O-[5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl]-oxime | |
3.5.1.108 | 0.027 | - |
- |
Escherichia coli | 5'-O-[(E)-(2,3,4-trihydroxybenzylidene)amino]uridine | |
3.5.1.108 | 0.03 | - |
- |
Escherichia coli | 3,4-dihydroxy-benzaldehyde O-[5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl]-oxime | |
3.5.1.108 | 0.12 | - |
- |
Escherichia coli | N-(((2R,3R,4S,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)-2-((Z)-2,3,4-trihydroxybenzylideneaminooxy)acetamide |