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26-10 Fab-digoxin complex: Affinity and specificity due to surface complementarity

Jeffrey, Philip D. and Strong, Roland K. and Sieker, Larry C. and Chang, Chieh Ying Y. and Campbell, Robert L. and Petsko, Gregory A. and Haber, Edgar and Margolies, Michael N. and Sheriff, Steven (1993) 26-10 Fab-digoxin complex: Affinity and specificity due to surface complementarity. Proceedings of the National Academy of Sciences of the United States of America, 90 (21). pp. 10310-10314. ISSN 0027-8424. PMCID PMC47764.

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We have determined the three-dimensional structures of the antigen-binding fragment of the anti-digoxin monoclonal antibody 26-10 in the uncomplexed state at 2.7 Å resolution and as a complex with digoxin at 2.5 Å resolution. Neither the antibody nor digoxin undergoes any significant conformational changes upon forming the complex. Digoxin interacts primarily with the antibody heavy chain and is oriented such that the carbohydrate groups are exposed to solvent and the lactone ring is buried in a deep pocket at the bottom of the combining site. Despite extensive interactions between antibody and antigen, no hydrogen bonds or salt links are formed between 26-10 and digoxin. Thus the 26-10-digoxin complex is unique among the known three-dimensional structures of antibody-antigen complexes in that specificity and high affinity arise primarily from shape complementarity.

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Additional Information:© 1993 National Academy of Sciences. Communicated by David R. Davies, June 24, 1993. We thank Drs. Joel Schildbach, Robert Bruccoleri, and Jiri Novotny for helpful discussions and Dr. Martha Ludwig for the use of her data collection facility. This work was supported in part by National Institutes of Health Grants PO1-HL19259 and RO1-HL47415.
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Issue or Number:21
PubMed Central ID:PMC47764
Record Number:CaltechAUTHORS:20141216-113004558
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Official Citation:26-10 Fab-digoxin complex: affinity and specificity due to surface complementarity P D Jeffrey, R K Strong, L C Sieker, C Y Chang, R L Campbell, G A Petsko, E Haber, M N Margolies, and S Sheriff PNAS 1993 90 (21) 10310-10314
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52869
Deposited By: Ruth Sustaita
Deposited On:16 Dec 2014 19:56
Last Modified:04 Jun 2020 19:45

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