This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
2ap2
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:2ap2.gif|left|200px]] | [[Image:2ap2.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_2ap2", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | | | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), |
| - | | | + | or leave the SCENE parameter empty for the default display. |
| - | + | --> | |
| - | + | {{STRUCTURE_2ap2| PDB=2ap2 | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''SINGLE CHAIN FV OF C219 IN COMPLEX WITH SYNTHETIC EPITOPE PEPTIDE''' | '''SINGLE CHAIN FV OF C219 IN COMPLEX WITH SYNTHETIC EPITOPE PEPTIDE''' | ||
| Line 27: | Line 24: | ||
[[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
