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Literature summary extracted from

  • Korntner, S.; Pomorski, A.; Krezel, A.; Bishop, A.C.
    Optimized allosteric inhibition of engineered protein tyrosine phosphatases with an expanded palette of biarsenical small molecules (2018), Bioorg. Med. Chem., 26, 2610-2620 .
    View publication on PubMedView publication on EuropePMC

Protein Variants

EC Number Protein Variants Comment Organism
3.1.3.48 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

EC Number Inhibitors Comment Organism Structure
3.1.3.48 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
3.1.3.48 4,6-bis(1,3,2-dithiarsolan-2-yl)-7-hydroxy-3H-phenoxazin-3-one i.e. ReAsH Homo sapiens
3.1.3.48 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
3.1.3.48 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
3.1.3.48 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]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
3.1.3.48 additional information
-
 additional information Michaelis-Menten kinetics 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 DADE(pY)LIPQQG + H2O Homo sapiens a physiological phosphopeptide substrate of enzyme PTP1B DADEYLIPQQG + phosphate
-
 ?
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
-
-

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 DADE(pY)LIPQQG + H2O a physiological phosphopeptide substrate of enzyme PTP1B Homo sapiens DADEYLIPQQG + phosphate
-
 ?
3.1.3.48 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
-
 ?
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

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
3.1.3.48 37
-
 assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
3.1.3.48 7
-
 assay at Homo sapiens

General Information

EC Number General Information Comment Organism
3.1.3.48 physiological function the phosphatase PTP1B is a key regulator of insulin and leptin signaling Homo sapiens