Preorganization and protein dynamics in enzyme catalysis

P. T.Ravi Rajagopalan, Stephen Benkovic

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Recently, an alternative has been offered to the concept of transition state (TS) stabilization as an explanation for rate enhancements in enzyme-catalyzed reactions. Instead, most of the rate increase has been ascribed to preorganization of the enzyme active site to bind substrates in a geometry close to that of the TS, which then transit the activation barrier impelled by motions along the reaction coordinate. The question as to how an enzyme achieves such preorganization and concomitant TS stabilization as well as potential coupled motions along the reaction coordinate leads directly to the role of protein dynamic motion. Dihydrofolate reductase (DHFR) is a paradigm in which the role of dynamics in catalysis continues to be unraveled by a wealth of kinetic, structural, and computational studies. DHFR has flexible loop regions adjacent to the active site whose motions modulate passage through the kinetically preferred pathway. The participation of residues distant from the DHFR active site in enhancing the rate of hydride transfer, however, is unanticipated and may signify the importance of long range protein motions. The general significance of protein dynamics in understanding other biological processes is briefly discussed.

Original languageEnglish (US)
Pages (from-to)24-36
Number of pages13
JournalChemical Record
Volume2
Issue number1
DOIs
StatePublished - Jan 1 2002

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Tetrahydrofolate Dehydrogenase
Catalysis
Enzymes
Proteins
Catalytic Domain
Stabilization
Biological Phenomena
Hydrides
Articular Range of Motion
Chemical activation
Kinetics
Geometry
Substrates
Oxidoreductases

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry
  • Chemical Engineering(all)
  • Materials Chemistry

Cite this

Rajagopalan, P. T.Ravi ; Benkovic, Stephen. / Preorganization and protein dynamics in enzyme catalysis. In: Chemical Record. 2002 ; Vol. 2, No. 1. pp. 24-36.
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Preorganization and protein dynamics in enzyme catalysis. / Rajagopalan, P. T.Ravi; Benkovic, Stephen.

In: Chemical Record, Vol. 2, No. 1, 01.01.2002, p. 24-36.

Research output: Contribution to journalArticle

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