2ap2
From Proteopedia
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'''SINGLE CHAIN FV OF C219 IN COMPLEX WITH SYNTHETIC EPITOPE PEPTIDE''' | '''SINGLE CHAIN FV OF C219 IN COMPLEX WITH SYNTHETIC EPITOPE PEPTIDE''' | ||
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[[Category: Elsen, J M.H Van Den.]] | [[Category: Elsen, J M.H Van Den.]] | ||
[[Category: Rose, D R.]] | [[Category: Rose, D R.]] | ||
| - | [[Category: | + | [[Category: C219]] |
| - | [[Category: | + | [[Category: Immunoglobulin]] |
| - | [[Category: | + | [[Category: Monoclonal antibody]] |
| - | [[Category: | + | [[Category: P-glycoprotein]] |
| - | [[Category: | + | [[Category: Single chain fv]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:18:31 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 16:18, 3 May 2008
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 Sat May 3 19:18:31 2008
