2nyy: Difference between revisions

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[[Image:2nyy.jpg|left|200px]]
{{Seed}}
[[Image:2nyy.png|left|200px]]


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{{STRUCTURE_2nyy|  PDB=2nyy  |  SCENE=  }}  
{{STRUCTURE_2nyy|  PDB=2nyy  |  SCENE=  }}  


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




==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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{{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]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 10:05:48 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 15:58:26 2008''

Revision as of 12:58, 28 July 2008

File:2nyy.png

Template:STRUCTURE 2nyy

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

Template:ABSTRACT PUBMED 17173035

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

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