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Preorganization and protein dynamics in enzyme catalysis
- Source :
- The Chemical Record. 2:24-36
- Publication Year :
- 2002
- Publisher :
- Wiley, 2002.
-
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. © 2002 The Japan Chemical Journal Forum and John Wiley & Sons, Inc." Chem Rec 2: 24–36, 2002
- Subjects :
- chemistry.chemical_classification
Binding Sites
biology
Protein Conformation
Chemistry
Stereochemistry
General Chemical Engineering
Protein dynamics
Active site
General Chemistry
Biochemistry
Catalysis
Enzymes
Enzyme catalysis
Reaction coordinate
Alcohol Oxidoreductases
Kinetics
Motion
Enzyme
Models, Chemical
Dihydrofolate reductase
Materials Chemistry
biology.protein
Dynamic motion
Subjects
Details
- ISSN :
- 15280691 and 15278999
- Volume :
- 2
- Database :
- OpenAIRE
- Journal :
- The Chemical Record
- Accession number :
- edsair.doi.dedup.....ce6207194afce12fe899c8c433e50ea8