2nyy

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[[Image:2nyy.jpg|left|200px]]
[[Image:2nyy.jpg|left|200px]]
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{{Structure
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The line below this paragraph, containing "STRUCTURE_2nyy", creates the "Structure Box" on the page.
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|SITE=
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|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
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{{STRUCTURE_2nyy| PDB=2nyy | SCENE= }}
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|RELATEDENTRY=[[2nz9|2NZ9]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2nyy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nyy OCA], [http://www.ebi.ac.uk/pdbsum/2nyy PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2nyy RCSB]</span>
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'''Crystal structure of botulinum neurotoxin type A complexed with monoclonal antibody CR1'''
'''Crystal structure of botulinum neurotoxin type A complexed with monoclonal antibody CR1'''
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[[Category: Arndt, J W.]]
[[Category: Arndt, J W.]]
[[Category: Stevens, R C.]]
[[Category: Stevens, R C.]]
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[[Category: botulinum]]
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[[Category: Botulinum]]
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[[Category: fab]]
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[[Category: Fab]]
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[[Category: neurotoxin]]
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[[Category: Neurotoxin]]
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[[Category: protein antibody complex]]
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[[Category: Protein antibody complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:05:48 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:10:24 2008''
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Revision as of 07:05, 4 May 2008

Image:2nyy.jpg

Template:STRUCTURE 2nyy

Crystal structure of botulinum neurotoxin type A complexed with monoclonal antibody CR1


Overview

Broadening antibody specificity without compromising affinity should facilitate detection and neutralization of toxin and viral subtypes. We used yeast display and a co-selection strategy to increase cross-reactivity of a single chain (sc) Fv antibody to botulinum neurotoxin type A (BoNT/A). Starting with a scFv that binds the BoNT/A1 subtype with high affinity (136 pM) and the BoNT/A2 subtype with low affinity (109 nM), we increased its affinity for BoNT/A2 1,250-fold, to 87 pM, while maintaining high-affinity binding to BoNT/A1 (115 pM). To find the molecular basis for improved cross-reactivity, we determined the X-ray co-crystal structures of wild-type and cross-reactive antibodies complexed to BoNT/A1 at resolutions up to 2.6 A, and measured the thermodynamic contribution of BoNT/A1 and A2 amino acids to wild-type and cross-reactive antibody binding. The results show how an antibody can be engineered to bind two different antigens despite structural differences in the antigen-antibody interface and may provide a general strategy for tuning antibody specificity and cross-reactivity.

About this Structure

2NYY is a Single protein structure of sequence from Clostridium botulinum. Full crystallographic information is available from OCA.

Reference

Molecular evolution of antibody cross-reactivity for two subtypes of type A botulinum neurotoxin., Garcia-Rodriguez C, Levy R, Arndt JW, Forsyth CM, Razai A, Lou J, Geren I, Stevens RC, Marks JD, Nat Biotechnol. 2007 Jan;25(1):107-16. Epub 2006 Dec 17. PMID:17173035 Page seeded by OCA on Sun May 4 10:05:48 2008

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