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The X-ray structure of an anti-tumour antibody in complex with antigen

Nature Structural Biology volume 2, pages 466–471 (1995)Cite this article

A Corrigendum to this article was published on 01 December 1996

Abstract

The crystal structures of the murine BR96 Fab and its human chimera have been determined in complex with the nonoate methyl ester derivative of Lewis Y (nLey) at 2.8 Å and 2.5 Å resolution, respectively. BR96 binds the carbohydrate in a large pocket which is formed by residues of all CDR loops except L2. The binding of the carbohydrate is mediated predominantly by aromatic residues in BR96. Analysis of the structure suggests that BR96 is capable of recognizing a structure larger than the Ley tetrasaccharide, providing a possible explanation for its high tumour selectivity. The structure provides a rationale for mutagenesis experiments that have resulted in BR96 CDR loop mutants with increased affinity for nLey and/or tumour cells.

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Author notes

  1. Philip D. Jeffrey

    Present address: Memorial Sloan-Kettering Cancer Center, Box 576, 1275 York Avenue, New York, New York, 10021, USA

Authors and Affiliations

  1. Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, New Jersey, 08543-4000, USA

    Philip D. Jeffrey, ChiehYing Y. Chang & Steven Sheriff

  2. Bristol-Myers Squibb Pharmaceutical Research Institute, 3005 First Avenue, Seattle, Washington, 98121, USA

    Jürgen Bajorath, Dale Yelton, Ingegerd Hellström & Karl Erik Hellström

Authors
  1. Philip D. Jeffrey
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  2. Jürgen Bajorath
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  3. ChiehYing Y. Chang
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  4. Dale Yelton
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  5. Ingegerd Hellström
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  6. Karl Erik Hellström
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  7. Steven Sheriff
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Jeffrey, P., Bajorath, J., Chang, C. et al. The X-ray structure of an anti-tumour antibody in complex with antigen. Nat Struct Mol Biol 2, 466–471 (1995). https://doi.org/10.1038/nsb0695-466

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