2ipu
From Proteopedia
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| - | [[Image:2ipu.jpg|left|200px]] | + | [[Image:2ipu.jpg|left|200px]] |
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| - | '''PFA1 Fab fragment complexed with Abeta 1-8 peptide''' | + | {{Structure |
| + | |PDB= 2ipu |SIZE=350|CAPTION= <scene name='initialview01'>2ipu</scene>, resolution 1.650Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=ACM:ACETAMIDE'>ACM</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''PFA1 Fab fragment complexed with Abeta 1-8 peptide''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2IPU is a [ | + | 2IPU is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IPU OCA]. |
==Reference== | ==Reference== | ||
| - | Molecular basis for passive immunotherapy of Alzheimer's disease., Gardberg AS, Dice LT, Ou S, Rich RL, Helmbrecht E, Ko J, Wetzel R, Myszka DG, Patterson PH, Dealwis C, Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15659-64. Epub 2007 Sep 25. PMID:[http:// | + | Molecular basis for passive immunotherapy of Alzheimer's disease., Gardberg AS, Dice LT, Ou S, Rich RL, Helmbrecht E, Ko J, Wetzel R, Myszka DG, Patterson PH, Dealwis C, Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15659-64. Epub 2007 Sep 25. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17895381 17895381] |
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: wwddd]] | [[Category: wwddd]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:32:14 2008'' |
Revision as of 15:32, 20 March 2008
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| , resolution 1.650Å | |||||||
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| Ligands: | and | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
PFA1 Fab fragment complexed with Abeta 1-8 peptide
Overview
Amyloid aggregates of the amyloid-beta (Abeta) peptide are implicated in the pathology of Alzheimer's disease. Anti-Abeta monoclonal antibodies (mAbs) have been shown to reduce amyloid plaques in vitro and in animal studies. Consequently, passive immunization is being considered for treating Alzheimer's, and anti-Abeta mAbs are now in phase II trials. We report the isolation of two mAbs (PFA1 and PFA2) that recognize Abeta monomers, protofibrils, and fibrils and the structures of their antigen binding fragments (Fabs) in complex with the Abeta(1-8) peptide DAEFRHDS. The immunodominant EFRHD sequence forms salt bridges, hydrogen bonds, and hydrophobic contacts, including interactions with a striking WWDDD motif of the antigen binding fragments. We also show that a similar sequence (AKFRHD) derived from the human protein GRIP1 is able to cross-react with both PFA1 and PFA2 and, when cocrystallized with PFA1, binds in an identical conformation to Abeta(1-8). Because such cross-reactivity has implications for potential side effects of immunotherapy, our structures provide a template for designing derivative mAbs that target Abeta with improved specificity and higher affinity.
About this Structure
2IPU is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
Reference
Molecular basis for passive immunotherapy of Alzheimer's disease., Gardberg AS, Dice LT, Ou S, Rich RL, Helmbrecht E, Ko J, Wetzel R, Myszka DG, Patterson PH, Dealwis C, Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15659-64. Epub 2007 Sep 25. PMID:17895381
Page seeded by OCA on Thu Mar 20 17:32:14 2008
Categories: Mus musculus | Protein complex | Dealwis, C. | Gardberg, A S. | ACM | GOL | Abeta | Cdr | Immune system | Wwddd
