Session III DISCUSSION 



S. E. Bresler (U.S.S.R.): 



Comment on the Papers of Pauling and Synge 



I shall deal with what appears to me to be an extremely important aspect of the problem 

 of proteins, namely the relation between structure and function. It is known that each 

 protein fulfils a definite functional task (or number of tasks) in the organism. Enzymic 

 activity is a typical example of a very important function. Evidence collected during 

 recent years shows that the enzymic activity does not reside in the macromolecule of 

 protein as a whole, but in a part of it known as the reactive centre. This was demonstrated 

 by experiments in which it was shown that fragments of the molecule of comparatively 

 low molecular weight, produced by proteolysis, possessed quite a considerable degree 

 of enzymic activity. I have carried out similar experiments (in conjunction with GUkina 

 and Frenkel) on aldolase and chymotrypsin. We carried out the separation of the active 

 fragments from the protein by means of an ultracentrifuge in a special preparative 

 cell. This allowed us to assign an upper limit to the molecular weight of the active par- 

 ticles. It was found to be of the order of 2000-3000 (i.e. to contain, on the average, 

 20-30 amino acid residues). A similar result was obtained at the same time by Gertrude 

 Pearlman using pepsin. She used dialysis to separate the active particles from the protein. 

 Finally, a little later on, Linderstrem-Lang and Anfinsen and their colleagues came to the 

 same conclusion about ribonuclease. This all shows that the enzymic function of the 

 protein is inherent in relatively small regions of the macromolecule. The structure of 

 the active centre is certainly strictly determinate. It often happens that the other parts of 

 the molecule can undergo profound chemical changes (in particular decomposition) 

 without any radical disturbance of the functional properties. These facts correspond with 

 important observations in other fields. Fraenkel-Conrat has shown that, in virus infections, 

 ribonucleic acid particles, having a molecular weight of the order of 200,000-300,000, are 

 infective. These particles contain within themselves the whole of the information required 

 for synthesizing the specific viral protein. As the mean molecular weight of the Unks in 

 the poljmucleotide chain is of the order of 400, the infective particles of ribonucleic acid 

 must contain about 500 Unks. It is clear that several Unks of the nucleotide chain must 

 correspond to one amino acid Unk in the polypeptide chain. This follows from the fact 

 that the order of succession of about 20 different amino acids is recorded by means of 

 4 different nucleotides (cf. the correspondence between the ordinary alphabet and the 

 alphabet of the Morse code). We do not yet know the nature of the code and so we cannot 

 say exactly how many nucleotide groups are needed to specify one amino acid group. 

 From logical considerations we may assume that the number is 2-3. A polynucleotide 

 chain of 500 Unks would therefore contain information about the structure of a polj^eptide 

 chain of 150-200 Unks, i.e. a protein having a molecular weight of the order of only 

 15,000-22,000. Again, we see that what is needed for the manifestation of fxmctional 

 activity need not be the whole protein (the protein part of the tobacco mosaic virus has a 

 molecular weight of about 2,000,000) but only some relatively small fragments of it. It is 

 natural to suppose that the structure of the molecule is strictly determinate only within 

 the limits of these functionally active fragments. In the other parts of the macromolecule 

 of the protein one might expect that there would only be a certain statistical mean arrange- 

 ment exhibiting certain common architectural features which confer stability on the pro- 

 tein, such as a large number of hydrogen bonds, a considerable number of hydrated 

 groups etc. There is nothing surprising in such a view of the case. We must not forget that 

 the proteins of contemporary Uving things which we have studied are the products of a 

 long process of evolution. As the evolutionary changes of organisms proceeded, some 

 proteins might retain their functions while others changed theirs, i.e. there has been a 



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