Quantifying energetic contributions to ground state destabilization.
Vibrational spectroscopy has identified that in many cases, substrate association with enzyme active sites results in significant bond polarization. This bond polarization can be attributed to a combination of desolvation, conformational restriction, and true polarization by the local electric field. Quantum chemical calculations permit the extent of polarization to be quantified both in terms of partial charge and energy. The changes in vibrational frequency that occur during the binding process necessarily result in equilibrium isotope effects. The equilibrium isotope effect on association is one feature that differentiates isotope effects on k(cat) and k(cat)/K(m). An improved chemical understanding of the changes that occur on substrate binding will help elucidate the role of substrate activation in enzyme catalysis.
Anderson
Vernon E
VE
Department of Biochemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4935, USA. vea@case.edu
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D004746:Enoyl-CoA Hydratase / Q000737:chemistry* / Q000378:metabolism*; D004795:Enzyme Stability; D006860:Hydrogen Bonding; D007535:Isomerases / Q000737:chemistry* / Q000378:metabolism*; D007554:Isotopes; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism*; D063994:Peroxisomal Bifunctional Enzyme; D011487:Protein Conformation; D011789:Quantum Theory; D013057:Spectrum Analysis / Q000379:methods; D013059:Spectrum Analysis, Raman; D013379:Substrate Specificity; D013816:Thermodynamics; D014732:Vibration
D007554:Isotopes; D009097:Multienzyme Complexes; D015094:3-Hydroxyacyl CoA Dehydrogenases; D004746:Enoyl-CoA Hydratase; D063994:Peroxisomal Bifunctional Enzyme; D007535:Isomerases