Interaction of Organic Molecules with 

 Proteins 



I. M. Klotz 



Northwestern University, Evanston, III. 



IN CONTRAST TO THE PRECEDING PAPER I should like to revcrt to the chemi- 

 cal level, instead of the quantum mechanical level, in describing some of 

 the interactions of organic molecules with proteins. 



Studies of these interactions with proteins other than the immune glob- 

 ulins have been carried out particularly intensively in the last 10 or so years, 

 and I think one can say without exaggeration that almost every factor which 

 one can possibly think of which might affect the strength of these interactions 

 has been examined to some extent, by somebody. I do not think it would be 

 profitable just to describe the wide variety of factors which are known to be 

 able to affect the strength of these complexes, even though that might be of in- 

 terest, let us say, to an enzymologist searching about for some possible models, 

 relatively simple models, with which to explain particular effects which he 

 may have observed. 



Instead, it seems to me more appropriate in a symposium of this type to 

 pick a few factors which show specificity of varying degrees and to see to what 

 extent we can account for and understand these specificities in terms of the 

 molecular structure of the participants. 



It has helped me, at least in picking and trying to interpret these phenomena, 

 to think of the effects of the factors which can affect the stability of the protein 

 complex with the small molecule as either residing in the environment outside 

 of the protein or being an expression of the protein structure itself. So what I 

 am going to do is pick two or three examples of each type: extrinsic factors 

 where even in the outside environment of the protein one can find specificities; 

 and intrinsic factors which will show certain similarities and dissimilarities, as 

 you will see, with the interactions with immune globulins. 



Let me proceed, then, first to take one or two examples which demonstrate 

 the effect of the environment on the strength of a protein complex. 



In the first figure (Fig. 1), largely for purposes of orientation, I would like 

 just to remind you that, if we represent a protein molecule schematically by a 

 sphere, protein molecules, particularly serum albumin, beta lactoglobulin 

 and to some extent, casein, can form complexes with organic molecules, which 

 I have indicated schematically as a smaller sized molecule (even though, from 

 some of the specific examples which you have seen, these can be fairly large). 



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