ABSTRACT
I. The Problem of Enzyme Catalysis .................................................................................. 766
A. Magnitudes of Catalytic Accelerations by Enzymes .............................................. 766
B. Transition-State Stabilization and Catalysis............................................................ 767
C. H-Bonds as a Means of Transition-State Stabilization ........................................... 768
D. Beyond the Transition-State Theory of Catalysis ................................................... 770
II. Structure and Strength of H-Bonds ................................................................................. 771
A. The Concept of H-Bond Strength............................................................................ 771
B. Categorization of H-Bonds ...................................................................................... 772
C. Some Probes of Hydrogen Bonds............................................................................ 772
1. NMR Approaches.............................................................................................. 773
2. Theoretical Studies of H-Bonds........................................................................ 773
3. Thermochemical, Spectroscopic, and Structural Approaches .......................... 774
III. Isotope Effects in Hydrogen Bonding ............................................................................. 775
A. Simple H-Bonds ....................................................................................................... 775
B. Unusual H-Bonds ..................................................................................................... 776
C. Primary Catalytic H-Bonds...................................................................................... 776
D. Secondary Catalytic H-Bonds.................................................................................. 777
IV. Issues in H-Bonding and Enzyme Catalysis ................................................................... 777
A. Cautionary Notes on Mutations at H-Bonding Sites in Enzymes .......................... 777
1. H-Bonds in the Orientation of Ligands for Optimal Catalysis ........................ 777
2. The Catalytic Triad of Serine Hydrolases ........................................................ 779
B. Primary Catalytic H-Bonds...................................................................................... 781
C. Secondary Catalytic H-Bonds.................................................................................. 781
1. The Catalytic Triad of Serine Hydrolases ........................................................ 781
2. The Oxyanion Hole of Serine Hydrolases........................................................ 785
D. Conformational Changes Signaled by Proton Inventories ...................................... 787
V. Summary .......................................................................................................................... 788
References..................................................................................................................................... 789
The kinetics of enzyme-catalyzed reactions (Lescovac;
Segel;
see also the chapter in this volume
by Cleland) are characterized for the most part by two kinds of rate constants, customarily given the
notation k
(a first-order rate constant, dimensions sec
, corresponding to the circumstance in
which the enzyme is fully saturated by substrates, reaction intermediates, or products as ligands)
and k
=K
(a second-order rate constant, dimensions M
sec
, corresponding to the
circumstance in which some form of the enzyme is reacting with a free substrate molecule). To
measure the magnitude of the catalytic acceleration produced by an enzyme, each of these rate
constants can be compared to the rate constant of a reaction not involving an enzyme, often called
the “uncatalyzed reaction” or sometimes the “standard reaction”.