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Science 4 March 1988:
Vol. 239. no. 4844, pp. 1105 - 1110
DOI: 10.1126/science.3125607
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Articles

Science, Vol 239, Issue 4844, 1105-1110
Copyright © 1988 by American Association for the Advancement of Science

articles

Insights into enzyme function from studies on mutants of dihydrofolate reductase

SJ Benkovic, CA Fierke, and AM Naylor

Department of Chemistry, Pennsylvania State University, University Park 16802.

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.


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