Electrostatic effects of bound NADH and NAD+ on ionizing groups in liver alcohol dehydrogenase.
A simple point charge model has been used to estimate the effect of electrostatic interactions of bound NADH and NAD+ on ionizing groups in liver alcohol dehydrogenase. The results provide clear evidence that the much-discussed effects of pH on coenzyme binding in the pH range 7-10 are predominantly of electrostatic origin and attributable to ionization of the water molecule which is bound at the active-site zinc ion. Ionization of Lys-228 is proposed to account for the proton-dependent destabilization of the enzyme X NADH and enzyme X NAD+ complexes which has been reported to occur above a pKa of 10.4.
D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000818:Animals; D004563:Electrochemistry; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D011485:Protein Binding
D009243:NAD; D000426:Alcohol Dehydrogenase