2nz9: Difference between revisions
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[[Image:2nz9.jpg|left|200px]] | [[Image:2nz9.jpg|left|200px]] | ||
'''Crystal structure of botulinum neurotoxin type A complexed with monoclonal antibody AR2''' | {{Structure | ||
|PDB= 2nz9 |SIZE=350|CAPTION= <scene name='initialview01'>2nz9</scene>, resolution 3.79Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=CA:CALCIUM ION'>CA</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] | |||
|GENE= | |||
}} | |||
'''Crystal structure of botulinum neurotoxin type A complexed with monoclonal antibody AR2''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2NZ9 is a [ | 2NZ9 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NZ9 OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17173035 17173035] | ||
[[Category: Bontoxilysin]] | [[Category: Bontoxilysin]] | ||
[[Category: Clostridium botulinum]] | [[Category: Clostridium botulinum]] | ||
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[[Category: protein antibody complex]] | [[Category: protein antibody complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:53:08 2008'' | ||
Revision as of 18:53, 20 March 2008
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| , resolution 3.79Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Bontoxilysin, with EC number 3.4.24.69 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of botulinum neurotoxin type A complexed with monoclonal antibody AR2
OverviewOverview
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 StructureAbout this Structure
2NZ9 is a Single protein structure of sequence from Clostridium botulinum. Full crystallographic information is available from OCA.
ReferenceReference
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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