2ap2
From Proteopedia
|
SINGLE CHAIN FV OF C219 IN COMPLEX WITH SYNTHETIC EPITOPE PEPTIDE
Overview
The ABC transporter, P-glycoprotein, is an integral membrane protein that, mediates the ATP-driven efflux of drugs from multidrug-resistant cancer, and HIV-infected cells. Anti-P-glycoprotein antibody C219 binds to both of, the ATP-binding regions of P-glycoprotein and has been shown to inhibit, its ATPase activity and drug binding capacity. C219 has been widely used, in a clinical setting as a tumor marker, but recent observations of, cross-reactivity with other proteins, including the c-erbB2 protein in, breast cancer cells, impose potential limitations in detecting, P-glycoprotein. We have determined the crystal structure at a resolution, of 2.4 A of the variable fragment of C219 in complex with an epitope, peptide derived from the nucleotide binding domain of P-glycoprotein. The, 14-residue peptide adopts an amphipathic alpha-helical conformation, a, secondary structure not previously observed in structures of, antibody-peptide complexes. Together with available biochemical data, the, crystal structure of the C219-peptide complex indicates the molecular, basis of the cross-reactivity of C219 with non-multidrug, resistance-associated proteins. Alignment of the C219 epitope with the, recent crystal structure of the ATP-binding subunit of histidine permease, suggests a structural basis for the inhibition of the ATP and drug binding, capacity of P-glycoprotein by C219. The results provide a rationale for, the development of C219 mutants with improved specificity and affinity, that could be useful in antibody-based P-glycoprotein detection and, therapy in multidrug resistant cancers.
About this Structure
2AP2 is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
Reference
Antibody C219 recognizes an alpha-helical epitope on P-glycoprotein., van Den Elsen JM, Kuntz DA, Hoedemaeker FJ, Rose DR, Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13679-84. PMID:10570132
Page seeded by OCA on Sun Nov 18 09:47:31 2007
