2nyy: Difference between revisions
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|PDB= 2nyy |SIZE=350|CAPTION= <scene name='initialview01'>2nyy</scene>, resolution 2.61Å | |PDB= 2nyy |SIZE=350|CAPTION= <scene name='initialview01'>2nyy</scene>, resolution 2.61Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[2nz9|2NZ9]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2nyy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nyy OCA], [http://www.ebi.ac.uk/pdbsum/2nyy PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2nyy RCSB]</span> | |||
}} | }} | ||
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[[Category: Arndt, J W.]] | [[Category: Arndt, J W.]] | ||
[[Category: Stevens, R C.]] | [[Category: Stevens, R C.]] | ||
[[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 04:10:24 2008'' | ||
Revision as of 01:10, 31 March 2008
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| 2nyy, resolution 2.61Å | |||||||||||||
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| Ligands: | CA, ZN | ||||||||||||
| Related: | 2NZ9
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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 CR1
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
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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