Insights into enzymic catalysis from studies on dihydrofolate reductases

Stephen J. Benkovic, Joseph A. Adams, Carol A. Fierke, Adel M. Naylor

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The role of DHFR in the maintenance of cellular DNA has sparked wide interest in the structure and dynamics of this enzyme. Kinetic studies of specific amino acid replacements on the enzyme isolated from E. coli has proved useful in the detailing of hydrophobic and ionic interactions both proximal and distal to the site of chemical transformation (e. g. Phe-31, Leu-54 and Arg-44). Despite the low sequence homology shared by the E. coli and L. easei enzymes, the free energy profiles are surprisingly comparable. This probably is the result of the high degree of structural similarity of the active site surfaces, but the deleterious effects of subtle replacements (e. g. Leu-54-Ile) at strictly conserved amino acids underscore the latters unique role in attaining the required catalytic efficiency for the enzyme.

Original languageEnglish (US)
Pages (from-to)37-43
Number of pages7
JournalPteridines
Volume1
Issue number1
DOIs
StatePublished - Feb 1989

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Clinical Biochemistry

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    Benkovic, S. J., Adams, J. A., Fierke, C. A., & Naylor, A. M. (1989). Insights into enzymic catalysis from studies on dihydrofolate reductases. Pteridines, 1(1), 37-43. https://doi.org/10.1515/pteridines.1989.1.1.37