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Structural Studies of Catalytic Antibodies

Stevens, Raymond C. and Hsieh-Wilson, Linda C. and Santarsiero, Bernard D. and Wedemayer, Gary J. and Spiller, Ben and Wang, Leo H. and Barnes, Dwight and Ulrich, Helle D. and Patten, Phillip A. and Romesberg, Floyd E. and Schultz, Peter G. (1996) Structural Studies of Catalytic Antibodies. Israel Journal of Chemistry, 36 (2). pp. 121-132. ISSN 0021-2148. http://resolver.caltech.edu/CaltechAUTHORS:20150520-093646814

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Abstract

A panel of catalytic antibodies which catalyze ester hydrolysis, transesterification, porphyrin metallation, Diels-Alder, and redox reactions has been selected for crystallographic study. While these examples are only a handful of the catalytic antibodies generated to date, they represent distinct and important aspects of antibody catalysis. Since the first reports of catalysis, a great deal of progress has been made with respect to the scope, selectivity, and efficiency of antibody catalysis and strategies for generating catalytic antibodies. However, it is clear that further progress in the field will benefit greatly from a detailed understanding of the molecular interactions occurring in the combining site. High-resolution crystallographic data should allow the importance of general base catalysis, entropy effects, electrophilic catalysis, and transition-state stabilization to be evaluated. Antibody and enzyme active sites have been shown to share considerable structural and mechanistic similarity, and ongoing structure-function studies of catalytic antibodies may enhance our understanding of the mechanisms and evolution of enzymatic catalysis. Structural studies of antibodies which perform a biological or highly selective reactions should enhance our ability to generate catalysts for important synthetic applications. Finally, the combination of high-resolution crystallographic analysis with rational mutagenesis should provide a basis for engineering antibodies with enhanced properties.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1002/ijch.199600018DOIArticle
http://onlinelibrary.wiley.com/doi/10.1002/ijch.199600018/abstractPublisherArticle
ORCID:
AuthorORCID
Hsieh-Wilson, Linda C.0000-0001-5661-1714
Additional Information:© 1996 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Special Issue: Catalytic Antibodies. (Received 11 September 1996 and in revisedform 25 September 1996). We are grateful for financial support for this work from the National Institutes of Health (Grant No. ROI AI24695) and the Director, Office of Energy Research, Division of Material Sciences and Division of Energy Biosciences, Office of General Life Sciences, Structural Biology Division, of the U.S. Department of Energy under Contract No. DE-AC03-76SF00098. P.G.S. is a Howard Hughes Medical Institute Investigator. L.C.H.-W. thanks the National Science Foundation and American Chemical Society for predoctoral fellowships. G.J.W. has received a post-doctoral fellowship from the Howard Hughes Medical Institute. We are grateful for synchrotron beamtime from the Stanford Synchrotron Radiation Laboratory, Beamline 7-1.
Funders:
Funding AgencyGrant Number
NIHROI AI24695
Department of Energy (DOE)DE-AC03-76SF00098
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NSF Predoctoral FellowshipUNSPECIFIED
American Chemical SocietyUNSPECIFIED
Record Number:CaltechAUTHORS:20150520-093646814
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20150520-093646814
Official Citation:Stevens, R. C., Hsieh-Wilson, L. C., Santarsiero, B. D., Wedemayer, G. J., Spiller, B., Wang, L. H., Barnes, D., Ulrich, H. D., Patten, P. A., Romesberg, F. E. and Schultz, P. G. (1996), Structural Studies of Catalytic Antibodies. Isr. J. Chem., 36: 121–132. doi: 10.1002/ijch.199600018
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:57694
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:20 May 2015 23:14
Last Modified:07 Nov 2017 23:16

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