2b2x

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{{STRUCTURE_2b2x| PDB=2b2x | SCENE= }}
{{STRUCTURE_2b2x| PDB=2b2x | SCENE= }}
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'''VLA1 RdeltaH I-domain complexed with a quadruple mutant of the AQC2 Fab'''
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===VLA1 RdeltaH I-domain complexed with a quadruple mutant of the AQC2 Fab===
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==Overview==
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Improving the affinity of a high-affinity protein-protein interaction is a challenging problem that has practical applications in the development of therapeutic biomolecules. We used a combination of structure-based computational methods to optimize the binding affinity of an antibody fragment to the I-domain of the integrin VLA1. Despite the already high affinity of the antibody (Kd approximately 7 nM) and the moderate resolution (2.8 A) of the starting crystal structure, the affinity was increased by an order of magnitude primarily through a decrease in the dissociation rate. We determined the crystal structure of a high-affinity quadruple mutant complex at 2.2 A. The structure shows that the design makes the predicted contacts. Structural evidence and mutagenesis experiments that probe a hydrogen bond network illustrate the importance of satisfying hydrogen bonding requirements while seeking higher-affinity mutations. The large and diverse set of interface mutations allowed refinement of the mutant binding affinity prediction protocol and improvement of the single-mutant success rate. Our results indicate that structure-based computational design can be successfully applied to further improve the binding of high-affinity antibodies.
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(as it appears on PubMed at http://www.pubmed.gov), where 16597831 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16597831}}
==About this Structure==
==About this Structure==
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[[Category: Antibody-antigen complex]]
[[Category: Antibody-antigen complex]]
[[Category: Computational design]]
[[Category: Computational design]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:46:58 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 00:59:31 2008''

Revision as of 21:59, 27 July 2008

Image:2b2x.png

Template:STRUCTURE 2b2x

VLA1 RdeltaH I-domain complexed with a quadruple mutant of the AQC2 Fab

Template:ABSTRACT PUBMED 16597831

About this Structure

2B2X is a Single protein structure of sequence from Mus musculus and Rattus norvegicus. Full crystallographic information is available from OCA.

Reference

Affinity enhancement of an in vivo matured therapeutic antibody using structure-based computational design., Clark LA, Boriack-Sjodin PA, Eldredge J, Fitch C, Friedman B, Hanf KJ, Jarpe M, Liparoto SF, Li Y, Lugovskoy A, Miller S, Rushe M, Sherman W, Simon K, Van Vlijmen H, Protein Sci. 2006 May;15(5):949-60. Epub 2006 Apr 5. PMID:16597831

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