Recombinant Human PGP protein

P-Glycoprotein (P-gp), encoded by the *ABCB1* gene, is a well-studied ATP-binding cassette (ABC) transporter first identified in 1976 for its role in multidrug resistance (MDR) in cancer. Overexpressed in tumor cells, P-gp actively effluxes chemotherapeutic agents, reducing intracellular drug accumulation and diminishing treatment efficacy. Its discovery revolutionized understanding of cellular detoxification mechanisms and drug transport. Structurally, P-gp consists of two homologous halves, each containing a transmembrane domain (TMD) for substrate recognition and a cytosolic nucleotide-binding domain (NBD) for ATP hydrolysis. This configuration enables ATP-driven translocation of diverse substrates, including anticancer drugs, antibiotics, and toxins.

Recombinant P-gp production, achieved via heterologous expression systems like mammalian cells (e.g., HEK293), insect cells, or yeast, allows detailed functional and structural studies. Escherichia coli-based systems are less common due to challenges in folding this large (~170 kDa), complex membrane protein. Purification typically involves affinity chromatography tags (e.g., His-tag) followed by reconstitution into lipid bilayers or detergent micelles for in vitro assays. Recombinant P-gp is pivotal in screening modulators to overcome MDR, analyzing drug-transporter interactions, and deciphering molecular mechanisms of ATP-coupled transport. Recent cryo-EM structures of human P-gp have revealed conformational changes during its transport cycle, informing drug design strategies. Beyond oncology, P-gp influences pharmacokinetics by limiting blood-brain barrier penetration or intestinal absorption of drugs, making its recombinant form essential for predicting drug disposition and toxicity. Ongoing research focuses on optimizing expression platforms, elucidating substrate specificity, and developing targeted inhibitors to enhance therapeutic outcomes.