342 2. ANALOCxS OF ENZYME REACTION COMPONENTS 



Table 2-16 

 Inhibition of Pig Kidney d-Amino Acid Oxidase by Aromatic Acids " 



Inhibitor 



Ki Relative — AF oi binding 



(mM) (kcal/mole) 



2-Chloromethyl-5-hydroxy-l,4-pyrone 



Kojate 



TO-Toluate 



Pjrrrole-2-carboxylate 



Benzoate 



Furan-2 -acrylate 



p-Toluate 



Nicotinate 



Cinnamate 



Furan-2-carboxylate 



l,2-Pyrone-5-carboxylate (coumalate) 



Indole-3-acetate 



Hydrocinnamate 



Phenylacetate 



l,4-Pyrone-2,6-dicarboxylate (chelidonate) 



o-Toluate 



"The substrate is DL-alanine and the pH 8.0-8.3. (Data from J. R. Klein, 1953, 1957.) 



data on aliphatic and heterocyclic carboxylates (Table 2-17). Some of the 

 conclusions regarding relations between structure and inhibition derived 

 from these investigations will be summarized. 



(1) A negatively charged anionic group is necessary for activity. This is 

 seen from the lack of inhibition by benzamide, nicotinamide, and cinnama- 

 mide. It is likely that the COO" group of the inhibitors reacts with the en- 

 zyme cationic site normally reacting with the amino acid C00~ group. A 

 SO3"" group can replace the COO" but is less effective. 



(2) Klein has emphasized the importance of a positive charge at a distance 

 from the COO" group approximating the separation in amino acids. Most 

 of the potent inhibitors can be written in structures possessing such a 

 positive charge by virtue of resonance effects. Benzoate, for example, 

 resonates between the following structures: 



- -J- 



/ \ / / \ 



v>\ ^% 



