Protein Variants | Comment | Organism |
---|---|---|
P87C/A122C | mutant asPTP1B, design of non-natural allosteric-inhibition sites in PTPs, in which a tricysteine moiety is engineered within the PTP catalytic domain at a conserved location outside of the active site. Introduction of the tricysteine motif, which does not exist in any wild-type PTP, serves to sensitize target PTPs to inhibition by a biarsenical compound, providing a generalizable strategy for the generation of allosterically sensitized (as) PTPs. The potency, selectivity, and kinetics of asPTP inhibition can be significantly improved by exploring the inhibitory action of a range of biarsenical compounds that differ in interarsenical distance, steric bulk, and electronic structure | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
2-[4,5-bis(1,3,2-dithiarsolan-2-yl)-6-hydroxy-3-oxo-3H-xanthen-9-yl]benzoic acid | i.e. FlAsH | Homo sapiens | |
4,6-bis(1,3,2-dithiarsolan-2-yl)-7-hydroxy-3H-phenoxazin-3-one | i.e. ReAsH | Homo sapiens | |
5-(1,3,2-dithiarsolan-2-yl)-2-[(1E,3E)-3-[5-(1,3,2-dithiarsolan-2-yl)-3,3-dimethyl-1-(4-sulfobutyl)-1,3-dihydro-2H-indol-2-ylidene]prop-1-en-1-yl]-3,3-dimethyl-1-(4-sulfobutyl)-3H-indol-1-ium | i.e. AsCy3, 70% inhibition at 250 nM AsCy3, AsCy3 is capable of specifically and potently inhibiting mutant enzyme asPTP1B in the presence of a complex proteome, while AsCy3 does not inhibit wild-type PTP1B activity in a cell lysate | Homo sapiens | |
5-(1,3,2-dithiarsolan-2-yl)-2-[(1E,3E,5E)-5-[5-(1,3,2-dithiarsolan-2-yl)-3,3-dimethyl-1-(4-sulfobutyl)-1,3-dihydro-2H-indol-2-ylidene]penta-1,3-dien-1-yl]-3,3-dimethyl-1-(4-sulfobutyl)-3H-indol-1-ium | i.e. AsCy5 | Homo sapiens | |
additional information | design of non-natural allosteric-inhibition sites in PTPs, in which a tricysteine moiety is engineered within the PTP catalytic domain at a conserved location outside of the active site. Introduction of the tricysteine motif, which does not exist in any wild-type PTP, serves to sensitize target PTPs to inhibition by a biarsenical compound, providing a generalizable strategy for the generation of allosterically sensitized (as) PTPs. Biarsenical reagents as enzyme inhibitors, overview. Enzyme asPTP catalytic domains have differing biarsenical sensitivities, with some being most potently inhibited by biarsenical compounds with large interarsenical distances, whereas others prefer compounds with relatively small interarsenical distances. AsCy3 is an optimized inhibitor of of engineered enzyme asPTP1B | Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | Michaelis-Menten kinetics | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
DADE(pY)LIPQQG + H2O | Homo sapiens | a physiological phosphopeptide substrate of enzyme PTP1B | DADEYLIPQQG + phosphate | - |
? | |
[a protein]-tyrosine phosphate + H2O | Homo sapiens | - |
[a protein]-tyrosine + phosphate | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P18031 | - |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
4-nitrophenyl phosphate + H2O | - |
Homo sapiens | 4-nitrophenol + phosphate | - |
? | |
DADE(pY)LIPQQG + H2O | a physiological phosphopeptide substrate of enzyme PTP1B | Homo sapiens | DADEYLIPQQG + phosphate | - |
? | |
DADE(pY)LIPQQG + H2O | a phosphopeptide substrate of enzyme PTP1B and the modified enzyme asPTP1B. asPTP1B dephosphorylates DADE(pY)LIPQQG at a rate that is only slightly lower than the rate of dephosphorylation induced by wild-type PTP1B | Homo sapiens | DADEYLIPQQG + phosphate | - |
? | |
[a protein]-tyrosine phosphate + H2O | - |
Homo sapiens | [a protein]-tyrosine + phosphate | - |
? |
Synonyms | Comment | Organism |
---|---|---|
protein tyrosine phosphatase | - |
Homo sapiens |
protein tyrosine phosphatase 1B | - |
Homo sapiens |
PTP | - |
Homo sapiens |
PTP1B | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7 | - |
assay at | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
physiological function | the phosphatase PTP1B is a key regulator of insulin and leptin signaling | Homo sapiens |