Crystal structure of a chimeric Fab′ fragment of an antibody binding tumour cells

R. L. Brady*, D. J. Edwards, R. E. Hubbard, J. S. Jiang, G. Lange, S. M. Roberts, R. J. Todd, J. R. Adair, J. S. Emtage, D. J. King, D. C. Low

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

52 Citations (Scopus)


The crystal structure of a chimeric Fab′ fragment of a monoclonal antibody is presented. The Fab′ comprises the murine light chain and heavy chain variable domains of the carcinoma-binding antibody B72.3 fused to the constant domain of human κ, and the first constant domain and hinge domain of human γ4, respectively. A model for the Fab′ has been determined by molecular replacement and refined to a resolution of 3·1 Å with an R-factor of 17·6%. The additional residues that distinguish a Fab′ from a Fab fragment are seen to be disordered in the crystals. The H3 hypervariable loop is short and adopts a sharp hairpin turn in a conformation that results from an interaction between the lysine side-chain of H93 and the main-chain carbonyl group of H96. The remaining hypervariable loops display conformations similar to those predicted from the canonical structures approach, although loop H2 is apparently displaced by a salt-bridge formed between H55 Asp and the neighbouring H73 Lys. These and other features of the structure likely to be important in grafting the hypervariable loops to an otherwise human framework are discussed.

Original languageEnglish
Pages (from-to)253-264
Number of pages12
JournalJournal of Molecular Biology
Issue number1
Publication statusPublished - 5 Sep 1992


  • antibody
  • antibody humanization
  • Fab′ fragment
  • molecular replacement
  • protein crystallography


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