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Insights into Enzyme Function from Studies on Mutants of Dihydrofolate Reductase

Benkovic, S. J. and Fierke, C. A. and Naylor, A. M. (1988) Insights into Enzyme Function from Studies on Mutants of Dihydrofolate Reductase. Science, 239 (4844). pp. 1105-1110. ISSN 0036-8075. http://resolver.caltech.edu/CaltechAUTHORS:20150107-145134535

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Abstract

Kinetic analysis and protein mutagenesis allow the importance of individual amino acids in ligand binding and catalysis to be assessed. A kinetic analysis has shown that the reaction catalyzed by dihydrofolate reductase is optimized with respect to product flux, which in turn is predetermined by the active-site hydrophobic surface. Protein mutagenesis has revealed that specific hydrophobic residues contribute 2 to 5 kilocalories per mole to ligand binding and catalysis. The extent to which perturbations within this active-site ensemble may affect catalysis is discussed in terms of the constraints imposed by the energy surface for the reaction.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.3125607DOIArticle
http://www.sciencemag.org/content/239/4844/1105PublisherArticle
http://www.jstor.org/stable/1700579JSTORArticle
Additional Information:© 1988 American Association for the Advancement of Science. We thank J.-T. Chen, R. Mayer, K. Taira, K. Johnson, J. Andrews, C. Singh, K. Houk, and Y.-D. Wu for their help and involvement in this work. We also thank W. A. Goddard III for use of the computer graphics facility for graphical displays. This work was supported in part by NIH grant GM24129 and DOE-ECUT 49-242-E0403-0-3550. C.A.F. is a NIH postdoctoral fellow.
Funders:
Funding AgencyGrant Number
NIHGM24129
Department of Energy (DOE)49-242-E0403-0-3550
NIH Postdoctoral FellowshipUNSPECIFIED
Record Number:CaltechAUTHORS:20150107-145134535
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20150107-145134535
Official Citation:Insights into enzyme function from studies on mutants of dihydrofolate reductase SJ Benkovic, CA Fierke, and AM Naylor Science 4 March 1988: 239 (4844), 1105-1110. [DOI:10.1126/science.3125607]
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:53297
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:08 Jan 2015 02:44
Last Modified:08 Jan 2015 02:44

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