Insights into enzyme function from studies on mutants of dihydrofolate reductase

S. J. Benkovic, C. A. Fierke, A. M. Naylor

Research output: Contribution to journalArticlepeer-review

132 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1105-1110
Number of pages6
JournalScience
Volume239
Issue number4844
DOIs
StatePublished - 1988

All Science Journal Classification (ASJC) codes

  • General

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