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Antibody C219 recognizes an a-helical epitope on P-glycoprotein

Proceedings of the National Academy of Sciences of the United States of America 96(24): 679-84

Antibody C219 recognizes an a-helical epitope on P-glycoprotein

The structure of the variable fragment (Fv) of the anti-P-glycoprotein C219 antibody in complex with an epitope derived from the nucleotide binding domain (NBD) of P-glycoprotein was characterized. P-glycoprotein is an ATP-binding cassette transporter that mediates the ATP-driven efflux of drugs from multidrug-resistant cancer cells and HIV-infected cells. X-ray crystallography at 2.4 A provided significant information on the molecular recognition of the cytosolic domains of P-glycoprotein by the antibody. In addition, the findings indicate a structural basis for cross-reactivity of C219, the inhibition of the ATP-driven drug-efflux pump, and binding of drugs to P-glycoprotein.

Accession: 009770353

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