P glycoprotein

P-glycoprotein (also known as permeability glycoprotein, or P-gp) is a well-characterized protein that functions as a cell membrane transporter. It is encoded by the MDR1 gene in humans. P-glycoprotein plays a crucial role in limiting drug absorption and distribution, as well as facilitating the excretion of drugs from the cells.

Structure

P-glycoprotein belongs to the ATP-binding cassette transporter superfamily. It is a 170-kDa protein that consists of two homologous halves, each containing six transmembrane domains and an ATP-binding site. The two halves are linked by a flexible linker region.

Function

P-glycoprotein acts as an ATP-dependent efflux pump, which expels substances out of the cells. It has broad substrate specificity and can transport a wide range of structurally diverse compounds out of the cells, including chemotherapeutic agents, steroids, immunosuppressants, HIV protease inhibitors, and many others.

Clinical significance

P-glycoprotein has significant clinical implications, particularly in pharmacology and oncology. Overexpression of P-glycoprotein can lead to multidrug resistance in cancer cells, which is a major obstacle in the successful treatment of many types of cancer. In addition, P-glycoprotein also affects the pharmacokinetics of many drugs and can cause drug-drug interactions.

Research

Research on P-glycoprotein has provided valuable insights into the mechanisms of multidrug resistance and has led to the development of several strategies to overcome this problem. These include the use of P-glycoprotein inhibitors, modulation of P-glycoprotein expression, and the design of drugs that are not substrates for this transporter.