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2nz9

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[[Image:2nz9.jpg|left|200px]]
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{{STRUCTURE_2nz9| PDB=2nz9 | SCENE= }}
{{STRUCTURE_2nz9| PDB=2nz9 | SCENE= }}
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'''Crystal structure of botulinum neurotoxin type A complexed with monoclonal antibody AR2'''
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===Crystal structure of botulinum neurotoxin type A complexed with monoclonal antibody AR2===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 17173035 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17173035}}
==About this Structure==
==About this Structure==
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[[Category: Neurotoxin]]
[[Category: Neurotoxin]]
[[Category: Protein antibody complex]]
[[Category: Protein antibody complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:06:41 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 16:44:18 2008''

Revision as of 13:44, 27 July 2008

Image:2nz9.png

Template:STRUCTURE 2nz9

Crystal structure of botulinum neurotoxin type A complexed with monoclonal antibody AR2

Template:ABSTRACT PUBMED 17173035

About this Structure

2NZ9 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 Jul 27 16:44:18 2008

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