2nz9
From Proteopedia
(New page: 200px<br /> <applet load="2nz9" size="450" color="white" frame="true" align="right" spinBox="true" caption="2nz9, resolution 3.79Å" /> '''Crystal structure o...) |
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caption="2nz9, resolution 3.79Å" /> | caption="2nz9, resolution 3.79Å" /> | ||
'''Crystal structure of botulinum neurotoxin type A complexed with monoclonal antibody AR2'''<br /> | '''Crystal structure of botulinum neurotoxin type A complexed with monoclonal antibody AR2'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2NZ9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum] with ZN and CA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Bontoxilysin Bontoxilysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.69 3.4.24.69] Full crystallographic information is available from [http:// | + | 2NZ9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Bontoxilysin Bontoxilysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.69 3.4.24.69] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NZ9 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: protein antibody complex]] | [[Category: protein antibody complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:40:07 2008'' |
Revision as of 15:40, 15 February 2008
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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 with and as ligands. Active as Bontoxilysin, with EC number 3.4.24.69 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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