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| - | [[Image:2ap2.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_2ap2| PDB=2ap2 | SCENE= }} | | {{STRUCTURE_2ap2| PDB=2ap2 | SCENE= }} |
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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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| - | ==Overview==
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| - | 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. | + | The line below this paragraph, {{ABSTRACT_PUBMED_10570132}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10570132 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_10570132}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: P-glycoprotein]] | | [[Category: P-glycoprotein]] |
| | [[Category: Single chain fv]] | | [[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 Mon Jul 28 23:38:00 2008'' |
Revision as of 20:38, 28 July 2008
Template:STRUCTURE 2ap2
SINGLE CHAIN FV OF C219 IN COMPLEX WITH SYNTHETIC EPITOPE PEPTIDE
Template:ABSTRACT PUBMED 10570132
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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