238 ANNUAL REPORT SMITHSONIAN INSTITUTION, 1950 



It is my opinion that the general problem of the nature of specific 

 biological forces has thus been solved, and that with the extension 

 of our knowledge of the detailed atomic structure of proteins and other 

 biological substances we may hope that this understanding will permit 

 a more effective attack to be made on many of the problems of biology 

 and medicine. 



NATURE OF ENZYMES 



I should like now to discuss a closely related question : the nature 

 of enzymes and of catalysts in general. In order to function, the liv- 

 ing cell carries out many specific chemical reactions that do not take 

 place when the reactants are simply mixed with one another. These 

 reactions occur in nature because there are present molecules of a 

 specific catalyst, the enzyme appropriate to the reaction. I believe 

 that an enzyme has a structure closely similar to that found for anti- 

 bodies, but with one important difference, namely, that the surface 

 configuration of the enzyme is not so closely complementary to its 

 specific substrate as is that of an antibody to its homologous antigen, 

 but is instead complementary to an unstable molecule with only 

 transient existence, the "activated complex," for the reaction that is 

 catalyzed by the enzyme. 



The mode of action of an enzyme would then be the following : the 

 enzyme would show a small power of attraction for the substrate 

 molecule or molecules, which would become attached to it in its active 

 surface region. This substrate molecule, or these molecules, would 

 then be strained by the forces of attraction for the enzyme, which 

 would tend to deform it into the configuration of the activated com- 

 plex, for which the power of attraction by the enzyme is the greatest. 

 The activated complex would then, under the influence of ordinary- 

 thermal agitation, either reassume the configuration corresponding 

 to the reactants, or assume the configuration corresponding to the 

 products. The assumption made above that the enzyme has a con- 

 figuration complementary to the activated complex, and accordingly 

 has the strongest power of attraction for the activated complex, means 

 that the activation energy for the reaction is less in the presence of 

 the enzyme than in its absence, and accordingly that the reaction 

 would be speeded up by the enzyme. My colleague Prof. Carl Nie- 

 mann and I are carrying out experiments on inhibition of enzyme 

 activity designed to test this postulate, by the search for inhibitors 

 that have a greater power of combination with the enzyme than have 

 the substrate molecules themselves. This method of attack should, 

 indeed, provide us with information about the nature of the active 

 region of the enzyme, if we accept the postulate that it is complemen- 

 tary to the configuration of the strong inhibitors. 



