190 LINUS PAULING 



importance in forming hydrogen bonds with carboxyHc groups. I wonder 

 whether tyrosine has not another particular importance in proteins. Tyrosine 

 has been accused, at least, for a long time of being responsible for the specificity 

 of proteins. For instance, tyrosine-free gelatin is not antigenic. I wonder 

 whether tyrosine actually has not a special strategic position in proteins be- 

 cause of its content of an aromatic ring. I suppose that Dr. Pressman's dia- 

 grams are over-simplifications and that he may mean that a benzene ring of 

 the aromatic inhibitors may actually fit somehow and lie closely parallel to 

 the benzene ring of tyrosine molecules. These would be London forces and not 

 van der Waals forces. 



Chairman Pauling: Perhaps I could say a word about the first question. 

 Why does the solubility of proteins change so rapidly with small changes in 

 structure? We might think that the solubility of a protein may be determined 

 by complementariness in structure of one part of the surface to another part 

 so that the molecules would tend to clamp onto one another and, since this 

 complementariness in structure can be destroyed by such a small change as 

 hydrogen to methyl, producing steric interference, the addition of oxygen atoms 

 might well cause just as great an interference. We have thought that it was a 

 special complementariness in structure of this sort that caused sickle-cell 

 anemia hemoglobin to have such low solubility, and that it was interference 

 with complementariness on oxygenation that caused the oxyhemoglobin to be 

 soluble again. This seems to me to be a satisfactory explanation. 



Dr. Anfinsen: I would like to say something about tyrosine. I did not 

 mean to imply that tyrosine has been proved to be involved in the active center 

 of ribonuclease. The only evidence for such involvement is the fact that 3 tyro- 

 sine hydroxyl-carboxyl interactions do seem to exist in this protein, and that 

 one of them appears to be ruptured during limited pepsin digestion, at a rate 

 paralleling both the loss of activity and the appearance of a free tetrapeptide 

 fragment. 



I suppose that I should also say a word about Dr. Pauling's earlier remarks. 

 There is now considerable evidence that the complete native protein structure 

 is not entirely essential in catalytic activity, not just in ribonuclease but in 

 other proteins as well. Although the resonating, macromolecular picture is 

 certainly intriguing and fun to think about, it seems worthwhile to consider the 

 possibility that small regions of proteins might serve adequately as catalytic 

 centers and that the size and complication of protein structure might have 

 developed for evolutionary reasons other than purely catalytic ones. 



Chairman Pauling: I think that in my discussion of enzymes I suggested 

 that the active region of an enzyme might be about the same size as the com- 

 bining region of one of the anti-haptenic antibodies, which is not very big. It 

 is a very little spot on a protein molecule. Then we may ask: What is the need 

 for the rest of the protein molecule? Some of it is needed in order to provide 



