Author: CINZIA BOFFA
P-glycoprotein (P-glycoprotein: multidrug-resistance and a superfamily of membrane-associated transport proteins. 1989)
Structure of P-Glycoprotein (Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. 2009)
The first crystal structure of a mammalian P-glycoprotein
Biochemical stucture of Pgp
Pgp is composed by:
Protein Aminoacids Percentage
- Eject out of cells a large variety of cytotoxic substances using energy derived by ATP-hydrolysis;
- This protein is present in healty cells (Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. 1987) and it is upregulated within tumor cells of individuals with increased resistance to chemiotherapy treatment (Expression of multidrug resistance proteins in prostate cancer is related with cell sensitivity to chemotherapeutic drugs. 2009";
- Pgp substrates include cytotoxic agents, the anthracyclines,the Vinca alkaloids, the taxanes and epipodofilotoxins and among the new antitumoral drugs, Imatinib (Functional consequence of MDR1 expression on Imatinib intracellular concentrations. 2003) and Gemtuzumab (Multidrug-resistance phenotype and clinical responses to Gentuzumab ozogamicin. 2001).
The anthracyclines (eg doxorubicin, daunorubicin and epirubicin) are some of the drugs most frequently used in the treatment of tumors (Analysis of drug transport kinetics in multidrug-resistant cells: implications for drug action. 2001).
Function of P-Glycoprotein
This transmembrane protein forms a pore to remove drug from the cell with an ATP-dependent mechanism. The energy is obtained by ATP hydrolysis; the binding of substrate to C-terminal stimulates the hydolysis of ATP into ADP + Pi that induce a Pgp conformational change resulting in a decrease of affinity for the substrate, which is tranferred first to the N-terminal site and then released outside the cell (The power of the pump: mechanisms of action of P-glycoprotein (ABCB1). 2006).