P-glycoproteins
P-glycoproteins were discovered as large cell membrane proteins overproduced in cancer cells resistant to a diverse set of hydrophobic drugs, so-called multidrug-resistant (MDR) cells.
P-glycoproteins were initially thought to affect the permeability of cells to drugs, but they were later found to act as pumps able to extrude drugs from cells at the cost of ATP hydrolysis.
P-glycoproteins belong to a class of vectorial transport proteins known as the ATP-binding cassette transporter proteins.
The cystic fibrosis transmembrane conductance regulator (CFTR) (MIM.602421) is a member of the family but functions as a chloride channel and has no known active transport function.
Defense against xenobiotics may be a major natural function of these P-glycoproteins.
The P-glycoproteins have 2 homologous halves, each with 6 hydrophobic segments adjacent to a consensus sequence for nucleotide binding. The hydrophobic segments may form a membrane channel, whereas the nucleotide binding site may be involved in energization of drug transport.