Molecular recognition by a binary code.

Frederic A Fellouse; Bing Li; Deanne M Compaan; Andrew A Peden; Sarah G Hymowitz; Sachdev S Sidhu

doi:10.1016/j.jmb.2005.03.041

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Molecular recognition by a binary code.

Frederic A Fellouse·Bing Li·Deanne M Compaan·Andrew A Peden·Sarah G Hymowitz·Sachdev S Sidhu

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Abstract

Functional antibodies were obtained from a library of antigen-binding sites generated by a binary code restricted to tyrosine and serine. An antibody raised against human vascular endothelial growth factor recognized the antigen with high affinity (K(D)=60 nM) and high specificity in cell-based assays. The crystal structure of another antigen binding fragment in complex with its antigen (human death receptor DR5) revealed the structural basis for this minimalist mode of molecular recognition. Natural antigen-binding sites are enriched for tyrosine and serine, and we show that these amino acid residues are intrinsically well suited for molecular recognition. Furthermore, these results demonstrate that molecular recognition can evolve from even the simplest chemical diversity.

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Amino Acid Sequence Antibodies Antibody Specificity Antigens Binding Sites, Antibody Crystallography Humans Immunoglobulin Fab Fragments Molecular Conformation Molecular Sequence Data Peptide Library Protein Conformation Receptors, TNF-Related Apoptosis-Inducing Ligand Receptors, Tumor Necrosis Factor Serine Tyrosine Vascular Endothelial Growth Factor A Journal Article Research Support, U.S. Gov't, Non-P.H.S.

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Frederic A Fellouse, Bing Li, Deanne M Compaan, Andrew A Peden, Sarah G Hymowitz, Sachdev S Sidhu. 2005-04-01. Molecular recognition by a binary code.. https://doi.org/10.1016/j.jmb.2005.03.041

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