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Literature summary extracted from
- Abietane-type diterpenoids inhibit protein tyrosine phosphatases by stabilizing an inactive enzyme conformation (2018), Biochemistry, 57, 5886-5896 .
No PubMed abstract available
Cloned(Commentary)
| EC Number | Cloned (Comment) | Organism |
|---|---|---|
| 3.1.3.48 | gene PTP1B, recombinant expression of C-terminally His-tagged wild-type and mutant enzymes (PTP1B residues 1-321) in Escherichia coli strain BL21(DE3) | Homo sapiens |
Protein Variants
| EC Number | Protein Variants | Comment | Organism |
|---|---|---|---|
| 3.1.3.48 | A122F | site-directed mutagenesis, affects inhibition by abietic acid and 2-[(carboxycarbonyl)amino]-4,5,6,7-tetrahydro-thieno[2,3-c]-pyridine-3-carboxylic acid | Homo sapiens |
| 3.1.3.48 | A122S | site-directed mutagenesis, affects inhibition by abietic acid | Homo sapiens |
| 3.1.3.48 | A189S | site-directed mutagenesis, affects inhibition by 3-(3,5-dibromo-4-hydroxybenzoyl)-2-ethylbenzofuran-6-sulfonic acid-[4-(thiazol-2-ylsulfamyl)phenyl]-amide and 2-[(carboxycarbonyl)amino]-4,5,6,7-tetrahydro-thieno[2,3-c]-pyridine-3-carboxylic acid | Homo sapiens |
| 3.1.3.48 | C92A | site-directed mutagenesis, affects inhibition by abietic acid and 2-[(carboxycarbonyl)amino]-4,5,6,7-tetrahydro-thieno[2,3-c]-pyridine-3-carboxylic acid | Homo sapiens |
| 3.1.3.48 | F135Y | site-directed mutagenesis, affects inhibition by abietic acid, 3-(3,5-dibromo-4-hydroxybenzoyl)-2-ethylbenzofuran-6-sulfonic acid-[4-(thiazol-2-ylsulfamyl)phenyl]-amide, and 2-[(carboxycarbonyl)amino]-4,5,6,7-tetrahydro-thieno[2,3-c]-pyridine-3-carboxylic acid | Homo sapiens |
| 3.1.3.48 | F182Y | site-directed mutagenesis, affects inhibition by abietic acid and 2-[(carboxycarbonyl)amino]-4,5,6,7-tetrahydro-thieno[2,3-c]-pyridine-3-carboxylic acid | Homo sapiens |
| 3.1.3.48 | F196Y | site-directed mutagenesis, affects inhibition by abietic acid and 2-[(carboxycarbonyl)amino]-4,5,6,7-tetrahydro-thieno[2,3-c]-pyridine-3-carboxylic acid | Homo sapiens |
| 3.1.3.48 | F280Y | site-directed mutagenesis, does not affect abietane-type diterpenoids as inhibitors | Homo sapiens |
| 3.1.3.48 | G259S | site-directed mutagenesis, affects inhibition by 2-[(carboxycarbonyl)amino]-4,5,6,7-tetrahydro-thieno[2,3-c]-pyridine-3-carboxylic acid | Homo sapiens |
| 3.1.3.48 | H175A | site-directed mutagenesis, affects inhibition by abietic acid and 2-[(carboxycarbonyl)amino]-4,5,6,7-tetrahydro-thieno[2,3-c]-pyridine-3-carboxylic acid | Homo sapiens |
| 3.1.3.48 | R112A | site-directed mutagenesis, affects inhibition by abietic acid, 3-(3,5-dibromo-4-hydroxybenzoyl)-2-ethylbenzofuran-6-sulfonic acid-[4-(thiazol-2-ylsulfamyl)phenyl]-amide, and 2-[(carboxycarbonyl)amino]-4,5,6,7-tetrahydro-thieno[2,3-c]-pyridine-3-carboxylic acid | Homo sapiens |
| 3.1.3.48 | V113T | site-directed mutagenesis, does not affect abietane-type diterpenoids as inhibitors | Homo sapiens |
| 3.1.3.48 | Y152A/Y153A | site-directed mutagenesis, the mutation attenuates allosteric communication between the C-terminus and the WPD loop, affects inhibition by abietic acid, 3-(3,5-dibromo-4-hydroxybenzoyl)-2-ethylbenzofuran-6-sulfonic acid-[4-(thiazol-2-ylsulfamyl)phenyl]-amide, and 2-[(carboxycarbonyl)amino]-4,5,6,7-tetrahydro-thieno[2,3-c]-pyridine-3-carboxylic acid | Homo sapiens |
Inhibitors
| EC Number | Inhibitors | Comment | Organism | Structure |
|---|---|---|---|---|
| 3.1.3.48 | 2-[(carboxycarbonyl)amino]-4,5,6,7-tetrahydro-thieno[2,3-c]-pyridine-3-carboxylic acid | i.e. TCS401, binds to the active site | Homo sapiens |  |
| 3.1.3.48 | 3-(3,5-dibromo-4-hydroxybenzoyl)-2-ethylbenzofuran-6-sulfonic acid-[4-(thiazol-2-ylsulfamyl)phenyl]-amide | i.e. BBR | Homo sapiens | |
| 3.1.3.48 | abietic acid | a nonpolar inhibitor and weak mixed-type inhibitor of PTP1B, inhibits the enzyme by binding to its active site in a nonsubstrate-like manner that stabilizes the catalytically essential WPD loop in an inactive conformation, modelling of enzyme binding. Upon binding to the active site, abietic acid forms a hydrogen bond with R221 that weakens a bond between R221 and E115 and prevents the formation of a hydrogen bond between W179 and R221 that forms when the WPD loop closes | Homo sapiens | |
| 3.1.3.48 | continentalic acid | modelling of enzyme binding | Homo sapiens | |
| 3.1.3.48 | dehydroabietic acid | modelling of enzyme binding | Homo sapiens | |
| 3.1.3.48 | dihydroabietic acid | modelling of enzyme binding | Homo sapiens | |
| 3.1.3.48 | isopimaric acid | modelling of enzyme binding | Homo sapiens | |
| 3.1.3.48 | additional information | abietane-type diterpenoids inhibit protein tyrosine phosphatases by stabilizing an inactive enzyme conformation. Abietane-type diterpenoids, a biologically active class of phytometabolites with largely nonpolar structures, are used for the development of pharmaceutically relevant PTP inhibitors. Minor changes in the structures of abietane-type diterpenoids (e.g. the addition of hydrogens) can improve potency (i.e. lower IC50) by several fold. Trodusquemine and benzofuran derivatives bind to C-terminal allosteric sites that attenuate WPD loop dynamics. Mechanisms of inhibition, dynamic docking, modelling, overview | Homo sapiens |
KM Value [mM]
| EC Number | KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|---|
| 3.1.3.48 | additional information | - |
additional information | Michaelis-Menten kinetic modeling | Homo sapiens |
Natural Substrates/ Products (Substrates)
| EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 3.1.3.48 | [a protein]-tyrosine phosphate + H2O | Homo sapiens | - |
[a protein]-tyrosine + phosphate | - |
? | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 3.1.3.48 | Homo sapiens | P18031 | - |
- |
Purification (Commentary)
| EC Number | Purification (Comment) | Organism |
|---|---|---|
| 3.1.3.48 | recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography | Homo sapiens |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 3.1.3.48 | 4-nitrophenyl phosphate + H2O | - |
Homo sapiens | 4-nitrophenol + phosphate | - |
? | |
| 3.1.3.48 | [a protein]-tyrosine phosphate + H2O | - |
Homo sapiens | [a protein]-tyrosine + phosphate | - |
? | |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 3.1.3.48 | protein tyrosine phosphatase | - |
Homo sapiens |
| 3.1.3.48 | protein tyrosine phosphatase 1B | - |
Homo sapiens |
| 3.1.3.48 | PTP | - |
Homo sapiens |
| 3.1.3.48 | PTP1B | - |
Homo sapiens |
General Information
| EC Number | General Information | Comment | Organism |
|---|---|---|---|
| 3.1.3.48 | physiological function | protein tyrosine phosphatase 1B is a negative regulator of insulin signaling | Homo sapiens |
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