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Literature summary for 7.6.2.2 extracted from

  • Eckford, P.D.; Sharom, F.J.
    Interaction of the P-glycoprotein multidrug efflux pump with cholesterol: effects on ATPase activity, drug binding and transport (2008), Biochemistry, 47, 13686-13698.
    View publication on PubMed
Search for more literature for 7.6.2.2

Inhibitors

Inhibitors Comment Organism Structure
cholesterol presence of cholesterol in the bilayer modulates the basal and drug-stimulated ATPase activity of reconstituted Pgp in vesicles. Both the ability of drugs to bind to the protein and the drug transport and phospholipid flippase functions of Pgp are also affected by cholesterol. The effects of cholesterol on drug binding affinity are unrelated to the size of the compound. Increasing cholesterol content greatly alters the partitioning of hydrophobic drug substrates into the membrane, which may account for some of the effects of cholesterol on Pgp-mediated drug transport Cricetulus griseus
methyl-beta-cyclodextrin over 85% inhibition of ATPase at 10 mM, about 55% inhibition of the lipid flippase at 10 mM Cricetulus griseus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information dissociation constants of transported substrates, effect of cholesterol on ATP and drug binding to reconstituted Pgp, overview Cricetulus griseus

Localization

Localization Comment Organism GeneOntology No. Textmining
cell surface of tumor cells Cricetulus griseus 9986
-
plasma membrane
-
 Cricetulus griseus 5886
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+
-
 Cricetulus griseus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + H2O + xenobiotic/in Cricetulus griseus expression at the tumor cell surface of P-glycoprotein, which functions as an ATP-powered multidrug efflux pump, is involved in multidrug resistance. It also shows lipid flippase activity ADP + phosphate + xenobiotic/out
-
 ?

Organism

Organism UniProt Comment Textmining
Cricetulus griseus
-
-
-

Purification (Commentary)

Purification (Comment) Organism
native P-gp by CHAPS-mediated extraction from plasma membrane, followed by concanavalin A affinity chromatography. Reconstitution in lipid proteoliposomes, that are further purified by gel filtration Cricetulus griseus

Source Tissue

Source Tissue Comment Organism Textmining
carcinoma cell
-
 Cricetulus griseus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + H2O + daunorubicin/in
-
 Cricetulus griseus ADP + phosphate + daunorubicin/out
-
 ?
ATP + H2O + H33342/in
-
 Cricetulus griseus ADP + phosphate + H33342/out
-
 ?
ATP + H2O + progesterone/in
-
 Cricetulus griseus ADP + phosphate + progesterone/out
-
 ?
ATP + H2O + rhodamine 123/in
-
 Cricetulus griseus ADP + phosphate + rhodamine 123/out
-
 ?
ATP + H2O + tetramethylrosamine/in
-
 Cricetulus griseus ADP + phosphate + tetramethylrosamine/out
-
 ?
ATP + H2O + vinblastine/in
-
 Cricetulus griseus ADP + phosphate + vinblastine/out
-
 ?
ATP + H2O + xenobiotic/in
-
 Cricetulus griseus ADP + phosphate + xenobiotic/out
-
 ?
ATP + H2O + xenobiotic/in expression at the tumor cell surface of P-glycoprotein, which functions as an ATP-powered multidrug efflux pump, is involved in multidrug resistance. It also shows lipid flippase activity Cricetulus griseus ADP + phosphate + xenobiotic/out
-
 ?

Synonyms

Synonyms Comment Organism
P-glycoprotein
-
 Cricetulus griseus
P-glycoprotein multidrug efflux pump
-
 Cricetulus griseus
Pgp
-
 Cricetulus griseus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
20
-
 ATP and substrate binding affinity assays at Cricetulus griseus
37
-
 ATPase assay at Cricetulus griseus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4 8.1 assay at, dependent on the solubility of participating components of the reconstituting proteoliposomes Cricetulus griseus

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Cricetulus griseus