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Literature summary for 3.4.24.56 extracted from

  • Im, H.; Manolopoulou, M.; Malito, E.; Shen, Y.; Zhao, J.; Neant-Fery, M.; Sun, C.Y.; Meredith, S.C.; Sisodia, S.S.; Leissring, M.A.; Tang, W.J.
    Structure of substrate-free human insulin-degrading enzyme (IDE) and biophysical analysis of ATP-induced conformational switch of IDE (2007), J. Biol. Chem., 282, 25453-25463.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
ADP activates, the activating effect of ATP is greater than hat of ADP, which in turn is much greater than that of AMP Homo sapiens
AMP activates, the activating effect of ATP is greater than hat of ADP, which in turn is much greater than that of AMP Homo sapiens
ATP activates the wild-type enzyme by about 300%, mutant D426C/K899C by about 50%, ATP enhances IDE activity by inducing a direct conformational change within individual IDE molecules, overview. The activating effect of ATP is greater than that of ADP, which in turn is much greater than that of AMP. The activation of IDE by ATP might be attributable to non-specific solvent effects rather than to specific interactions with a bona fide nucleotide binding domain Homo sapiens
CTP
-
Homo sapiens
GTP
-
Homo sapiens
additional information purine nucleotide triphosphates are better activators than pyrimidine nucleotide triphosphates Homo sapiens
TTP
-
Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
expression of wild-type and mutant enzymes in HEK-293swe.3 cells, that stably expresses Myc-epitope tagged human APP-695 harboring the FAD-linked, socalled Swedish mutation Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
purified recombinant mutant E11Q in complex with peptide substrate, and substrate-free mutant Y831F, hanging drop vapour diffusion method, 0.001 ml of 15-20 mg/ml protein and 0.001 ml of crystallization solution, containing 10-13% PEGMME 5000, 100 mM HEPES, pH 7.0, 4-14% Tacsimate, and 10% dioxane, are mixed and equilibrated with 0.5 ml of well solution at 18 °C, 3-5 days, cryoprotection by 15-30% glycerol, X-ray diffraction structure determination and analysis at 2.8-3.0 A resolution, modeling Homo sapiens

Protein Variants

Protein Variants Comment Organism
D426C/K899C site-directed mutagenesis, hyperactive IDE mutation, the mutant shows increased activity, but reduced activationby ATP compared to the wild-type enzyme Homo sapiens
E111Q site-directed mutagenesis, inactive mutant Homo sapiens
Y831F site-directed mutagenesis, the mutant shows catalytic activity similar to the wild-type enzyme Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
1,10-phenanthroline
-
Homo sapiens
bacitracin the inhibitory effect in enhanced by ATP Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.025
-
amyloid beta-peptide1-40 recombinant wild-type enzyme, pH 7.4, 37°C Homo sapiens
0.027
-
amyloid beta-peptide1-40 recombinant mutant D426C/K899C, pH 7.4, 37°C Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Zn2+ a zinc metalloprotease, the catalytic water that is coordinated by a zinc ion also interacts with a glutamate residue, which serves as the general acid/base catalyst Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
amyloid beta-peptide + H2O Homo sapiens degradation, IDE has no effect on the secreted ectodomain of the amyloid precursor protein derivative generated by alpha-secretase ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P14735
-
-

Purification (Commentary)

Purification (Comment) Organism
wild-type and mutant enzymes Homo sapiens

Reaction

Reaction Comment Organism Reaction ID
Degradation of insulin, glucagon and other polypeptides. No action on proteins Glu111 serves as a base to activate a catalytic water molecule within the active site of the enzyme, mediating peptide hydrolysis, mutation of this residue to glutamine renders IDE inactive, the catalytic water that is coordinated by a zinc ion also interacts with a glutamate residue, which serves as the general acid/base catalyst, catalytic mechanism Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(7-methoxycoumarin-4-yl)acetyl-RPPGFSAFK-2,4-dinitrophenyl + H2O
-
Homo sapiens ?
-
?
amyloid beta-peptide + H2O degradation, IDE has no effect on the secreted ectodomain of the amyloid precursor protein derivative generated by alpha-secretase Homo sapiens ?
-
?
amyloid beta-peptide1-40 + H2O degradation Homo sapiens ?
-
?
o-aminobenzoic acid-GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl + H2O
-
Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
IDE
-
Homo sapiens
Insulin-degrading enzyme
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
22
-
assay at, substrate o-aminobenzoic acid-GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl Homo sapiens
37
-
assay at, substrates amyloid beta-peptide and (7-methoxycoumarin-4-yl)acetyl-RPPGFSAFK-2,4-dinitrophenyl Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
8
-
amyloid beta-peptide1-40 recombinant wild-type enzyme, pH 7.4, 37°C Homo sapiens
8
-
amyloid beta-peptide1-40 recombinant wild-type enzyme, pH 7.4, 37°C Triticum aestivum
20
-
amyloid beta-peptide1-40 recombinant mutant D426C/K899C, pH 7.4, 37°C Homo sapiens
20
-
amyloid beta-peptide1-40 recombinant mutant D426C/K899C, pH 7.4, 37°C Triticum aestivum

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.3
-
assay at, substrate (7-methoxycoumarin-4-yl)acetyl-RPPGFSAFK-2,4-dinitrophenyl Homo sapiens
7.4
-
assay at, substrates amyloid beta-peptide and o-aminobenzoic acid-GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.11
-
recombinant wild-type enzyme, in in presence of ATP Homo sapiens bacitracin
0.18
-
recombinant mutant D426C/K899C, in in presence of ATP Homo sapiens bacitracin
0.2
-
recombinant mutant D426C/K899C, in absence of ATP Homo sapiens bacitracin
0.4
-
recombinant wild-type enzyme, in absence of ATP Homo sapiens bacitracin