Insights into the structure and substrate interactions of the P-glycoprotein multidrug transporter from spectroscopic studies.
The P-glycoprotein multidrug transporter is a 170-kDa efflux pump which exports a diverse group of natural products, chemotherapeutic drugs, and hydrophobic peptides across the plasma membrane, driven by ATP hydrolysis. The transporter has been proposed to interact with its drug substrates within the membrane environment; however, much remains to be learned about the nature and number of the drug binding site(s). The two nucleotide binding domains are responsible for ATP binding and hydrolysis, which is coupled to drug movement across the membrane. In recent years, P-glycoprotein has been purified and functionally reconstituted in amounts large enough to allow biophysical studies. The use of spectroscopic techniques has led to insights into both its secondary and tertiary structure, and its interaction with nucleotides and drugs. In this review, we will summarise what has been learned by application to purified P-glycoprotein of fluorescence spectroscopy, circular dichroism spectroscopy and infra-red spectroscopy.
Sharom
F J
FJ
Guelph-Waterloo Centre for Graduate Work in Chemistry and Biochemistry, Department of Chemistry and Biochemistry, University of Guelph, Guelph, Ont., Canada. sharom@chembio.uoguelph.ca
Liu
R
R
Romsicki
Y
Y
Lu
P
P
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry* / Q000302:isolation & purification; D000255:Adenosine Triphosphate / Q000737:chemistry; D000817:Anilino Naphthalenesulfonates; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism; D002942:Circular Dichroism; D047908:Intracellular Signaling Peptides and Proteins; D008051:Lipid Bilayers / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D012995:Solubility; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D013379:Substrate Specificity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000817:Anilino Naphthalenesulfonates; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008051:Lipid Bilayers; C089765:NUBP1 protein, human; D004364:Pharmaceutical Preparations; C021310:2-(4'-maleimidylanilino)naphthalene-6-sulfonic acid; D000255:Adenosine Triphosphate