Hydrogen bonds and proton transfer in general-catalytic transition-state stabilization in enzyme catalysis.
The question of the nature of the proton bridge involved in general acid-base catalysis in both enzymic and non-enzymic systems is considered in the light of long-known but insufficiently appreciated work of Jencks and his coworkers and of more recent results from neutron-diffraction crystallography and NMR spectroscopic studies, as well as results from isotope-effect investigations. These lines of inquiry lead toward the view that the bridging proton, when between electronegative atoms, is in a stable potential at the transition state, not participating strongly in the reaction-coordinate motion. Furthermore they suggest that bond order is well-conserved at unity for bridging protons, and give rough estimates of the degree to which the proton will respond to structural changes in its bonding partners. Thus if a center involved in general-catalytic bridging becomes more basic, the proton is expected to move toward it while maintaining a unit total bond order. For a unit increase in the pK of a bridging partner, the other partner is expected to acquire about 0.06 units of negative charge. The implications are considered for charge distribution in enzymic transition states as the basicity of catalytic residues changes in the course of molecular evolution or during progress along a catalytic pathway.
Schowen
K B
KB
Department of Chemistry and Higuchi Biosciences Center, 115 Simons Laboratories, University of Kansas, Lawrence 66045, USA.
Limbach
H H
HH
Denisov
G S
GS
Schowen
R L
RL
D002384:Catalysis; D003461:Crystallography; D004798:Enzymes / Q000737:chemistry*; D006860:Hydrogen Bonding; D007554:Isotopes; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008962:Models, Theoretical; D018892:Proton-Motive Force; D011522:Protons; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D004798:Enzymes; D007554:Isotopes; D011522:Protons