Implications for Enzymic Catalysis from Free-energy Reaction Coordinate Profiles
This extract was created in the absence of an abstract.
Excerpt
The power of pre-steady-state techniques employing stopped-flow and rapid-quench methods or of steady-state measurements combining isotope-effect techniques has provided a number of examples of free-energy reaction profiles for differing enzymes; dihydrofolate reductase (Fierke et al. 1987), DNA polymerase I (Kuchta et al. 1987), mechanochemical ATPases (Johnson 1985), and triosephosphate isomerase (Albery and Knowles 1976a). Such detailed descriptions have provided impressive, valuable insights into the coupling between the overall thermodynamic free-energy change for the given reaction and specific steps in the kinetic sequence for enzyme turnover (Jencks 1986) and have furnished predictions about the relationship between the ground- and transition-state levels for enzyme-ligand complexes for enzymes operating at high catalytic efficiency as a consequence of evolution (Albery and Knowles 1976b, 1977; Chin 1983; Stackhouse et al. 1985). In this paper, we describe the free-energy reaction rate profiles for these enzymes; Escherichia coli dihydrofolate reductase (DHFR), the Klenow fragment of DNA polymerase...
