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Literature summary for 3.1.3.48 extracted from

  • Hengge, A.C.
    Kinetic isotope effects in the characterization of catalysis by protein tyrosine phosphatases (2015), Biochim. Biophys. Acta, 1854, 1768-1775 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.1.3.48

Protein Variants

Protein Variants Comment Organism
D356N site-directed mutagenesis, a general acid mutant, catalytically inactive mutant, altered kinetic isotopic effects compared to wild-type Yersinia sp.
R409K site-directed mutagenesis, the kcat for the R409K mutant of YopH is lower by four orders of magnitude and kinetic isotopic effects resemble those for the general acid mutant D356N Yersinia sp.
W179F site-directed mutagenesis, the mutation in PTP1B causes only a minor reduction in kcat of about 2fold at pH 5.5, and the pH-rate profile remains fully bell-shaped. The kinetic isotopic effects are similar to those of the wild-type PTP1B showing that general acid catalysis remains effective. The affinity of the competitive inhibitors tungstate and molybdate for the active site is not affected by the W179F mutation. Crystal structures of the W179F mutant of PTP1B show the availability of both the normal loop open and closed positions, consistent with the kinetic results Homo sapiens
W354A site-directed mutagenesis, the more drastic mutation to alanine in this position (W354A) results in a further reduction in rate compared to W354F, a full flattening of the basic limb of the pH-rate profile, and kinetic isotopic effects that are consistent with total loss of general acid catalysis. The W354A mutant cannot be crystallized, but the kinetic and kinetic isotopic effect data suggest that the WPD loop positioning is more compromised than in mutant W354F, and not even partial neutralization of the leaving group is possible Yersinia sp.
W354F site-directed mutagenesis, the mutation in YopH results in a decrease in kcat by two orders of magnitude, loss of the basic limb of the pH-rate profile, and kinetic isotopic effects consistent with the leaving group departing as the anion, the mutant hsows an impaired general acid catalysis. The WPD loop in this mutant is immobile, fixed in a quasi-open position that leaves the Asp 356 side chain too far from the active site to effectively protonate the leaving group. The intermediate position of the WPD-loop in the W354F mutant evidently permits an intervening water molecule, bridging the aspartic acid and the substrate, to partially neutralize the leaving group during 4-nitrophenyl phosphate catalysis. The W354F mutation in YopH reduces the binding affinity for tungstate by about 6fold Yersinia sp.

Inhibitors

Inhibitors Comment Organism Structure
molybdate competitive inhibition Homo sapiens
molybdate competitive inhibition Yersinia sp.
tungstate competitive inhibition Homo sapiens
tungstate competitive inhibition Yersinia sp.

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information kinetic isotope effects. In the Stp reaction protonation of the leaving group lags behind P-O bond cleavage, evidenced by the small normal 15(V/K) values indicating a partial negative charge on the leaving group, as well as the more normal 18(V/K)bridge KIEs. The active form of the substrate is the dianion Schizosaccharomyces pombe
additional information
-
 additional information kinetic isotope effects. In the VHZ reaction protonation of the leaving group lags behind P-O bond cleavage, evidenced by the small normal 15(V/K) values indicating a partial negative charge on the leaving group, as well as the more normal 18(V/K)bridge KIEs. The active form of the substrate is the dianion Homo sapiens
additional information
-
 additional information kinetic isotope effects. The active form of the substrate is the dianion Yersinia sp.
additional information
-
 additional information kinetic isotope effects. The active form of the substrate is the dianion Homo sapiens
additional information
-
 additional information kinetic isotope effects. The active form of the substrate is the dianion Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol
-
 Schizosaccharomyces pombe 5829
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
[a protein]-tyrosine phosphate + H2O Yersinia sp.
-
 [a protein]-tyrosine + phosphate
-
 ?
[a protein]-tyrosine phosphate + H2O Homo sapiens
-
 [a protein]-tyrosine + phosphate
-
 ?
[a protein]-tyrosine phosphate + H2O Mus musculus
-
 [a protein]-tyrosine + phosphate
-
 ?
[a protein]-tyrosine phosphate + H2O Schizosaccharomyces pombe
-
 [a protein]-tyrosine + phosphate
-
 ?
[a protein]-tyrosine phosphate + H2O Schizosaccharomyces pombe ATCC 24843
-
 [a protein]-tyrosine + phosphate
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens P18031
-
-
Homo sapiens P51452
-
-
Homo sapiens Q9BVJ7
-
-
Mus musculus P35821
-
-
Schizosaccharomyces pombe P41893
-
-
Schizosaccharomyces pombe ATCC 24843 P41893
-
-
Yersinia sp.
-
-
-

Reaction

Reaction Comment Organism Reaction ID
[a protein]-tyrosine phosphate + H2O = [a protein]-tyrosine + phosphate for both alkyl and aryl substrates, including the activated substrate 4-nitrophenyl phosphate with its particularly good leaving group, general acid catalysis in PTPs is highly efficient and fully neutralizes the leaving group in the transition state. Mutating the conserved aspartic acid to glutamine causes the expected reductions in rate of several orders of magnitude and loss of the basic limb in pH-rate profiles, kinetic isotope effects, general acid catalysis mechanism, overview Yersinia sp.
a
[a protein]-tyrosine phosphate + H2O = [a protein]-tyrosine + phosphate for both alkyl and aryl substrates, including the activated substrate 4-nitrophenyl phosphate with its particularly good leaving group, general acid catalysis in PTPs is highly efficient and fully neutralizes the leaving group in the transition state. Mutating the conserved aspartic acid to glutamine causes the expected reductions in rate of several orders of magnitude and loss of the basic limb in pH-rate profiles, kinetic isotope effects, general acid catalysis mechanism, overview Homo sapiens
a
[a protein]-tyrosine phosphate + H2O = [a protein]-tyrosine + phosphate for both alkyl and aryl substrates, including the activated substrate 4-nitrophenyl phosphate with its particularly good leaving group, general acid catalysis in PTPs is highly efficient and fully neutralizes the leaving group in the transition state. Mutating the conserved aspartic acid to glutamine causes the expected reductions in rate of several orders of magnitude and loss of the basic limb in pH-rate profiles, kinetic isotope effects, general acid catalysis mechanism, overview Mus musculus
a
[a protein]-tyrosine phosphate + H2O = [a protein]-tyrosine + phosphate for both alkyl and aryl substrates, including the activated substrate 4-nitrophenyl phosphate with its particularly good leaving group, general acid catalysis in PTPs is highly efficient and fully neutralizes the leaving group in the transition state. Mutating the conserved aspartic acid to glutamine causes the expected reductions in rate of several orders of magnitude and loss of the basic limb in pH-rate profiles, kinetic isotope effects, general acid catalysis mechanism, overview Schizosaccharomyces pombe
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information human protein VHR is a dual specificity protein phosphatase 3, that also exhibits serine/threonine phosphatase activity, EC 3.1.3.16 Homo sapiens ?
-
 ?
additional information PTP1 is a classical PTP with a deep active site pocket suited for phosphotyrosine, that also efficiently hydrolyzes other phosphorylated phenols Mus musculus ?
-
 ?
additional information PTP1B is a classical PTP with a deep active site pocket suited for phosphotyrosine, that also efficiently hydrolyzes other phosphorylated phenols Homo sapiens ?
-
 ?
additional information Stp1 is a low molecular weight cytosolic acid phosphatase or phosphotyrosine protein phosphatase Schizosaccharomyces pombe ?
-
 ?
additional information VHZ is an atypical PTP, with the deep active site of classical PTPs but several structural differences, including an immobile loop bearing the general acid Homo sapiens ?
-
 ?
additional information YopH is a classical PTP with a deep active site pocket suited for phosphotyrosine, that also efficiently hydrolyzes other phosphorylated phenols Yersinia sp. ?
-
 ?
additional information Stp1 is a low molecular weight cytosolic acid phosphatase or phosphotyrosine protein phosphatase Schizosaccharomyces pombe ATCC 24843 ?
-
 ?
[a protein]-tyrosine phosphate + H2O
-
 Yersinia sp. [a protein]-tyrosine + phosphate
-
 ?
[a protein]-tyrosine phosphate + H2O
-
 Homo sapiens [a protein]-tyrosine + phosphate
-
 ?
[a protein]-tyrosine phosphate + H2O
-
 Mus musculus [a protein]-tyrosine + phosphate
-
 ?
[a protein]-tyrosine phosphate + H2O
-
 Schizosaccharomyces pombe [a protein]-tyrosine + phosphate
-
 ?
[a protein]-tyrosine phosphate + H2O
-
 Schizosaccharomyces pombe ATCC 24843 [a protein]-tyrosine + phosphate
-
 ?

Synonyms

Synonyms Comment Organism
dual specificity protein phosphatase 23 UniProt Homo sapiens
dual specificity protein phosphatase 3 UniProt Homo sapiens
LDP-3 UniProt Homo sapiens
low molecular mass dual specificity phosphatase 3 UniProt Homo sapiens
Low molecular weight phosphotyrosine protein phosphatase UniProt Schizosaccharomyces pombe
More cf. EC 3.1.3.16 Homo sapiens
protein tyrosine phosphatase
-
 Yersinia sp.
protein tyrosine phosphatase
-
 Homo sapiens
protein tyrosine phosphatase
-
 Mus musculus
protein tyrosine phosphatase
-
 Schizosaccharomyces pombe
protein-tyrosine phosphatase
-
 Yersinia sp.
protein-tyrosine phosphatase
-
 Homo sapiens
protein-tyrosine phosphatase
-
 Mus musculus
protein-tyrosine phosphatase
-
 Schizosaccharomyces pombe
PTP
-
 Yersinia sp.
PTP
-
 Homo sapiens
PTP
-
 Mus musculus
PTP
-
 Schizosaccharomyces pombe
PTP1
-
 Mus musculus
PTP1B
-
 Homo sapiens
PTPN1
-
 Mus musculus
Stp1
-
 Schizosaccharomyces pombe
VHR
-
 Homo sapiens
VHZ
-
 Homo sapiens
YopH
-
 Yersinia sp.

General Information

General Information Comment Organism
evolution the enzyme is a member of the PTP superfamily. The Trp residue is highly conserved in the PTP family and is one of the residues in the flexible loop that bears the general acid Homo sapiens
evolution the enzyme is a member of the PTP superfamily. The Trp residue is highly conserved in the PTP family and is one of the residues in the flexible loop that bears the general acid Mus musculus
evolution the enzyme is a member of the PTP superfamily. The Trp residue is highly conserved in the PTP family and is one of the residues in the flexible loop that bears the general acid Schizosaccharomyces pombe
evolution the enzyme is a member of the PTP superfamily. The Trp residue, W179 in PTP1B, is highly conserved in the PTP family and is one of the residues in the flexible loop that bears the general acid Homo sapiens
evolution the enzyme is a member of the PTP superfamily. The Trp residue, W354 in YopH, is highly conserved in the PTP family and is one of the residues in the flexible loop that bears the general acid Yersinia sp.
additional information phosphatases do not alter the transition state for phosphoryl transfer Homo sapiens
additional information phosphatases do not alter the transition state for phosphoryl transfer Mus musculus
additional information phosphatases do not alter the transition state for phosphoryl transfer Schizosaccharomyces pombe
additional information phosphatases do not alter the transition state for phosphoryl transfer. Active site structure and WPD loop analysis Yersinia sp.
additional information phosphatases do not alter the transition state for phosphoryl transfer. Active site structure and WPD loop analysis. Slowlier loop dynamics in PTP1B may reflect its key physiological roles in which turnover rates must meet the requirements of other activities in the cell Homo sapiens