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Literature summary 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

Activating Compound

EC Number Activating Compound Comment Organism Structure
7.6.2.1 cholesterol the transport activity of P-glycoprotein is elevated by about 40% cholesterol Cricetulus griseus
7.6.2.1 verapamil a P-glycoprotein modulator known to stimulate ATPase activity in a biphasic manner at micromolar concentrations Cricetulus griseus

Inhibitors

EC Number Inhibitors Comment Organism Structure
7.6.2.1 cholesterol the transport activity of P-glycoprotein decreases by about 20% cholesterol Cricetulus griseus
7.6.2.1 methyl-beta-cyclodextrin transport of 0.001 mM tetramethylrosamine is essentially abolished by 1 mM methyl-beta-cyclodextrin, and transport of 0.005 mM H33342 is almost completely inhibited by 5 mM methyl-beta-cyclodextrin Cricetulus griseus
7.6.2.2 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
7.6.2.2 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]

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

Localization

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

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
7.6.2.2 Mg2+
-
Cricetulus griseus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
7.6.2.2 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

EC Number Organism UniProt Comment Textmining
7.6.2.1 Cricetulus griseus
-
-
-
7.6.2.2 Cricetulus griseus
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
7.6.2.1 concanavalin A-Sepharose 4B affinity column chromatography and Sephadex G50 gel filtration Cricetulus griseus
7.6.2.2 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

EC Number Source Tissue Comment Organism Textmining
7.6.2.1 CHRB30 cell
-
Cricetulus griseus
-
7.6.2.2 carcinoma cell
-
Cricetulus griseus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
7.6.2.1 ATP + H2O + H33342/out
-
Cricetulus griseus ADP + phosphate + H33342/in
-
?
7.6.2.1 ATP + H2O + phosphatidylcholine/out
-
Cricetulus griseus ADP + phosphate + phosphatidylcholine/in
-
?
7.6.2.1 ATP + H2O + tetramethylrosamine/out
-
Cricetulus griseus ADP + phosphate + tetramethylrosamine/in
-
?
7.6.2.2 ATP + H2O + daunorubicin/in
-
Cricetulus griseus ADP + phosphate + daunorubicin/out
-
?
7.6.2.2 ATP + H2O + H33342/in
-
Cricetulus griseus ADP + phosphate + H33342/out
-
?
7.6.2.2 ATP + H2O + progesterone/in
-
Cricetulus griseus ADP + phosphate + progesterone/out
-
?
7.6.2.2 ATP + H2O + rhodamine 123/in
-
Cricetulus griseus ADP + phosphate + rhodamine 123/out
-
?
7.6.2.2 ATP + H2O + tetramethylrosamine/in
-
Cricetulus griseus ADP + phosphate + tetramethylrosamine/out
-
?
7.6.2.2 ATP + H2O + vinblastine/in
-
Cricetulus griseus ADP + phosphate + vinblastine/out
-
?
7.6.2.2 ATP + H2O + xenobiotic/in
-
Cricetulus griseus ADP + phosphate + xenobiotic/out
-
?
7.6.2.2 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

EC Number Synonyms Comment Organism
7.6.2.1 ABCB1
-
Cricetulus griseus
7.6.2.1 P-glycoprotein functions as an ATP-powered multidrug efflux pump for amphipathic molecules Cricetulus griseus
7.6.2.2 P-glycoprotein
-
Cricetulus griseus
7.6.2.2 P-glycoprotein multidrug efflux pump
-
Cricetulus griseus
7.6.2.2 Pgp
-
Cricetulus griseus

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
7.6.2.2 20
-
ATP and substrate binding affinity assays at Cricetulus griseus
7.6.2.2 37
-
ATPase assay at Cricetulus griseus

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
7.6.2.2 7.4 8.1 assay at, dependent on the solubility of participating components of the reconstituting proteoliposomes Cricetulus griseus

Cofactor

EC Number Cofactor Comment Organism Structure
7.6.2.2 ATP
-
Cricetulus griseus