2nz9
From Proteopedia
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|PDB= 2nz9 |SIZE=350|CAPTION= <scene name='initialview01'>2nz9</scene>, resolution 3.79Å | |PDB= 2nz9 |SIZE=350|CAPTION= <scene name='initialview01'>2nz9</scene>, resolution 3.79Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2nyy|2NYY]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2nz9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nz9 OCA], [http://www.ebi.ac.uk/pdbsum/2nz9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2nz9 RCSB]</span> | ||
}} | }} | ||
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[[Category: Arndt, J W.]] | [[Category: Arndt, J W.]] | ||
[[Category: Stevens, R C.]] | [[Category: Stevens, R C.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: ZN]] | ||
[[Category: botulinum]] | [[Category: botulinum]] | ||
[[Category: fab]] | [[Category: fab]] | ||
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[[Category: protein antibody complex]] | [[Category: protein antibody complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:10:32 2008'' |
Revision as of 01:10, 31 March 2008
| |||||||
| , resolution 3.79Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Bontoxilysin, with EC number 3.4.24.69 | ||||||
| Related: | 2NYY
| ||||||
| 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
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