2nz9
From Proteopedia
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| , resolution 3.79Å | |||||||
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| Ligands: | , | ||||||
| Activity: | Bontoxilysin, with EC number 3.4.24.69 | ||||||
| Related: | 2NYY
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of botulinum neurotoxin type A complexed with monoclonal antibody AR2
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
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 Mon Mar 31 04:10:32 2008
