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Literature summary for 7.6.2.2 extracted from

  • Kimura, Y.; Kioka, N.; Kato, H.; Matsuo, M.; Ueda, K.
    Modulation of drug-stimulated ATPase activity of human MDR1/P-glycoprotein by cholesterol (2007), Biochem. J., 401, 597-605.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 7.6.2.2

Activating Compound

Activating Compound Comment Organism Structure
campesterol enhances paclitaxel-stimulated ATPase activity of enzyme Homo sapiens
cholesterol presence of cholesterol in liposomes increases the binding affinity of small drug substrates with molecular masses below 500 Da, does not affect that of drugs with molecular mass of between 800 and 900 Da, and suppresses that of valinomycin with a molecular mass greater than 1000. Cholesterol enhances paclitaxel-stimulated ATPase activity of enzyme Homo sapiens
sitosterol enhances paclitaxel-stimulated ATPase activity of enzyme Homo sapiens
stigmasterol enhances paclitaxel-stimulated ATPase activity of enzyme Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
expression in insect cells Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
cholesterol presence of cholesterol in liposomes increases the binding affinity of small drug substrates with molecular masses below 500 Da, does not affect that of drugs with molecular mass of between 800 and 900 Da, and suppresses that of valinomycin with a molecular mass greater than 1000 Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0009
-
 ATP pH 7.5, 37°C, paclitaxel-stimulated ATPase activity, presence of 20% ergosterol Homo sapiens
0.001
-
 ATP pH 7.5, 37°C, paclitaxel-stimulated ATPase activity, presence of 20% campesterol Homo sapiens
0.001
-
 nicardipine/in pH 7.5, 37°C, presence of 20% cholesterol Homo sapiens
0.0011
-
 ATP pH 7.5, 37°C, paclitaxel-stimulated ATPase activity, presence of 20% sitosterol Homo sapiens
0.0013
-
 paclitaxel pH 7.5, 37°C, presence of 5% cholesterol Homo sapiens
0.0013
-
 vinblastine/in pH 7.5, 37°C, presence of 5% cholesterol Homo sapiens
0.0014
-
 paclitaxel pH 7.5, 37°C Homo sapiens
0.0014
-
 ATP pH 7.5, 37°C, paclitaxel-stimulated ATPase activity Homo sapiens
0.0014
-
 ATP pH 7.5, 37°C, paclitaxel-stimulated ATPase activity, presence of 20% stigmasterol Homo sapiens
0.0015
-
 nicardipine/in pH 7.5, 37°C, presence of 5% cholesterol Homo sapiens
0.0016
-
 ATP pH 7.5, 37°C, paclitaxel-stimulated ATPase activity, presence of 20% cholesterol Homo sapiens
0.0016
-
 paclitaxel pH 7.5, 37°C, presence of 20% cholesterol Homo sapiens
0.0016
-
 vinblastine/in pH 7.5, 37°C, presence of 20% cholesterol Homo sapiens
0.0017
-
 vinblastine/in pH 7.5, 37°C Homo sapiens
0.0022
-
 verapamil pH 7.5, 37°C, presence of 20% cholesterol Homo sapiens
0.0022
-
 valinomycin/in pH 7.5, 37°C, presence of 5% cholesterol Homo sapiens
0.0025
-
 valinomycin/in pH 7.5, 37°C Homo sapiens
0.0026
-
 nicardipine/in pH 7.5, 37°C Homo sapiens
0.0027
-
 vincristine pH 7.5, 37°C, presence of 5% cholesterol Homo sapiens
0.0035
-
 valinomycin/in pH 7.5, 37°C, presence of 20% cholesterol Homo sapiens
0.0037
-
 vincristine pH 7.5, 37°C Homo sapiens
0.0038
-
 verapamil pH 7.5, 37°C, presence of 5% cholesterol Homo sapiens
0.0039
-
 vincristine pH 7.5, 37°C, presence of 20% cholesterol Homo sapiens
0.0041
-
 verapamil pH 7.5, 37°C Homo sapiens
0.007
-
 rhodamine B pH 7.5, 37°C, presence of 20% cholesterol Homo sapiens
0.009
-
 rhodamine B pH 7.5, 37°C, presence of 5% cholesterol Homo sapiens
0.01
-
 rhodamine 123 pH 7.5, 37°C, presence of 20% cholesterol Homo sapiens
0.014
-
 rhodamine B pH 7.5, 37°C Homo sapiens
0.016
-
 rhodamine 123 pH 7.5, 37°C, presence of 5% cholesterol Homo sapiens
0.021
-
 rhodamine 123 pH 7.5, 37°C Homo sapiens
0.076
-
 digoxin pH 7.5, 37°C, presence of 20% cholesterol Homo sapiens
0.12
-
 digoxin pH 7.5, 37°C, presence of 5% cholesterol Homo sapiens
0.181
-
 digoxin pH 7.5, 37°C Homo sapiens
0.394
-
 dexamethasone pH 7.5, 37°C, presence of 20% cholesterol Homo sapiens
0.527
-
 dexamethasone pH 7.5, 37°C, presence of 5% cholesterol Homo sapiens
0.826
-
 dexamethasone pH 7.5, 37°C Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens the drug substrate binding site of isoform MDR1/P-glycoprotein may best fit to drugs with a molecular mass of between 800 and 900 Da, and cholesterol may support the recognition of smaller drugs by adjusting the drug-binding site ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
 isoform MDR1/P-glycoprotein
-

Purification (Commentary)

Purification (Comment) Organism
recombinant protein, reconstitution in proteoliposomes containing varying concentrations of cholesterol Homo sapiens

Renatured (Commentary)

Renatured (Comment) Organism
reconstitution of purified recombinant protein in proteoliposomes containing varying concentrations of cholesterol Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + H2O
-
 Homo sapiens ADP + phosphate
-
 ?
ATP + H2O + nicardipine/in
-
 Homo sapiens ADP + phosphate + nicardipine/out
-
 ?
ATP + H2O + valinomycin/in
-
 Homo sapiens ADP + phosphate + valinomycin/out
-
 ?
ATP + H2O + vinblastine/in
-
 Homo sapiens ADP + phosphate + vinblastine/out
-
 ?
dexamethasone/in + ATP + H2O
-
 Homo sapiens dexamethasone/out + ADP + phosphate
-
 ?
digoxin/in + ATP + H2O
-
 Homo sapiens digoxin/out + ADP + phosphate
-
 ?
additional information the drug substrate binding site of isoform MDR1/P-glycoprotein may best fit to drugs with a molecular mass of between 800 and 900 Da, and cholesterol may support the recognition of smaller drugs by adjusting the drug-binding site Homo sapiens ?
-
 ?
nicardipine/in + ATP + H2O
-
 Homo sapiens nicardipine/out + ADP + phosphate
-
 ?
paclitaxel/in + ATP + H2O
-
 Homo sapiens paclitaxel/out + ADP + phosphate
-
 ?
rhodamine 123/in + ATP + H2O
-
 Homo sapiens rhodamine 123/out + ADP + phosphate
-
 ?
rhodamine B/in + ATP + H2O
-
 Homo sapiens rhodamine B/out + ADP + phosphate
-
 ?
valinomycin/in + ATP + H2O
-
 Homo sapiens valinomycin/out + ADP + phosphate
-
 ?
verapamil/in + ATP + H2O
-
 Homo sapiens verapamil/out + ADP + phosphate
-
 ?
vinblastine/in + ATP + H2O
-
 Homo sapiens vinblastine/out + ADP + phosphate
-
 ?
vincristine/in + ATP + H2O
-
 Homo sapiens vincristine/out + ADP + phosphate
-
 ?