Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 3.1.3.48 extracted from

  • Brandao, T.A.; Hengge, A.C.; Johnson, S.J.
    Insights into the reaction of protein tyrosine phosphatase 1B. Crystal structures for transition-state analogs of both catalytic steps (2010), J. Biol. Chem., 285, 15874-15883.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
drug development the enzyme is a target for inhibitor design Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
two transition-state analogues, by sitting drop vapor diffusion method, 4°C, mixing of 0.002 ml of protein solution, containing native PTPB1, peptide DADEYL, and Na3VO4 in 10 mM Tris, pH 7.5, 25 mM NaCl, 0.2 mM EDTA, and 3 mM DTT, with 0.0005 ml of sucrose 30% v/v solution, and 0.003 ml of precipitant solution, containing 0.1 M HEPES, pH 7.5, 0.2 M magnesium acetate and 15-17% PEG 8000, 3 days, X-ray diffraction structure determination and analysis at 2.25-2.3 A resolution Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
vanadate the equatorial vanadate oxygen atoms bind to the P-loop and assumes a trigonal bipyramidal geometry in both transition state analogue structures, with very similar apical O-O distances, binding structure, overview Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.58
-
4-nitrophenyl phosphate pH 5.5, 25°C Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P18031
-
-

Reaction

Reaction Comment Organism Reaction ID
[a protein]-tyrosine phosphate + H2O = [a protein]-tyrosine + phosphate ping-pong mechanism, catalysis proceeds through a two-step mechanism involving a phosphocysteine intermediate. In the first step, a nucleophilic cysteine thiolate attacks the phosphate ester moiety of the substrate, resulting in formation of a phosphoenzyme intermediate with release of the peptidyl tyrosine. The second step occurs via attack of water on the phosphoenzyme intermediate, and yields the final products inorganic phosphate and the regenerated enzyme. The central binding site for the substrate is the P-loop, a region at the bottom of a pocket that includes the nucleophilic cysteine and backbone amide groups oriented in a horseshoe fashion, catalytic cycle, detailed overview Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
4-nitrophenyl phosphate + H2O
-
Homo sapiens 4-nitrophenol + phosphate
-
?
additional information formation and structure of a transition state analogue for the first catalytic step comprising a ternary complex between the catalytic cysteine of PTP1B, vanadate, and the peptide DADEYL, a fragment of a physiological substrate, overview. The equatorial vanadate oxygen atoms bind to the P-loop, and the apical positions are occupied by the peptide tyrosine oxygen and by the PTP1B cysteine sulfur atom. The vanadate assumes a trigonal bipyramidal geometry in both transition state analogue structures, with very similar apical O-O distances, denoting similar transition states for both phosphoryl transfer steps Homo sapiens ?
-
?

Subunits

Subunits Comment Organism
More PTPB1 possesses a P-loop, a WPD-loop, a Q-loop, a Lys-loop, and a pTyr-recognition loop, that show conformational changes during formation of the transition state Homo sapiens

Synonyms

Synonyms Comment Organism
protein tyrosine phosphatase 1B
-
Homo sapiens
PTP1B
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
assay at Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
24.4
-
4-nitrophenyl phosphate pH 5.5, 25°C Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
5.5
-
assay at Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.024
-
4-nitrophenyl phosphate pH 5.5, 25°C Homo sapiens