Role of the N-terminus of glutathione in the action of yeast glyoxalase I.
A number of S-substituted glutathiones and the corresponding N-substituted S-substituted analogues have been found to be linear competitive inhibitors of yeast glyoxalase I at 26 degrees C over the pH range 4.6-8.5. N-Acetylation of S-(p-bromobenzyl)glutathione weakens binding by 13.7-fold. N-benzoylation by 25.6-fold, N-trimethylacetylation by 53.3-fold and N-carbobenzoxylation by 7.8-fold, indicating a minor steric component in the binding at the N-site. The Ki-weakening effect of N-substitution of glutathione depends on the chemical nature of the S-substituent, indicating flexibility in the glutathione and/or glyoxalase I contributions to the binding site for glutathione derivatives. The effect of N-acylation on Ki is in accord with a charge interaction of the free enzyme with S-blocked glutathione in a region of reasonably high dielectric constant. There is a slight pH effect on Ki for S-(m-trifluoromethylbenzyl)glutathione but not for S-(p-bromobenzyl)glutathione.
D001665:Binding Sites; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008190:Lyases / Q000378:metabolism*; D013329:Structure-Activity Relationship
D008190:Lyases; D007791:Lactoylglutathione Lyase; D005978:Glutathione