INHIBITION OF SUCCINATE DEHYDROGENASE 43 



different distances apart. Since malonate is usually bound more tightly 

 than succinate, and much more than oxalate, it is reasonable to assume an 

 intercationic distance approximating the intercarboxylate distance in mal- 

 onate. It is by no means necessary that the substrate in its free configu- 

 ration exactly fits the enzyme site. Pauling (1946, 1948) has suggested, 

 " an active region of the surface of the enzyme... is closely complementary 

 in structure not to the substrate molecule itself, in its normal configuration, 

 but rather to the substrate molecule in a strained configuration, correspond- 

 ing to the activated complex for the reaction catalyzed by the enzyme." 

 Now, the fact that malonate fits the active site well does not mean that the 

 enzyme cationic groups are the same distance apart as the carboxylate 

 groups (3.28 A). The calculations above indicate a distance of 4.3 A 

 between carboxylate and cationic groups and thus, depending on the 

 geometry of the binding, the cationic groups could be much farther apart 

 than 3.28 A. Extreme situations are shown in Fig. 1-7, where the intercat- 



FiG. 1-7. Representations for the ex- 

 treme situa/tions in the interaction of 

 malonate with the two cationic groups 

 on the surface of succinate dehydro- 

 genase. In both cases (A and B) the 

 interaction distances and the energies 

 between the ionic groups are the same. 



ionic distance may vary from 3.28 to 13.1 A, approximately the same energy 

 of binding being expected in either case. Situation A is not very likely 

 because it is improbable that protein cationic groups would occur so close, 

 and, furthermore, in this case oxalate might be expected to bind quite well. 

 Also, situation B would provide more opportunity for succinate to be dehy- 

 drogenated at the enzyme surface. Of course, the enzyme surface at the 



