2ap2
From Proteopedia
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| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ap2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ap2 OCA], [http://www.ebi.ac.uk/pdbsum/2ap2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ap2 RCSB]</span> | ||
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[[Category: single chain fv]] | [[Category: single chain fv]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:55:27 2008'' |
Revision as of 22:55, 30 March 2008
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| , resolution 2.4Å | |||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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
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