8 J. C. KENDREW 



In the Fourier synthesis the side-chains can be seen as dense regions 

 emerging from the hehcal main chain at intervals corresponding to the 

 parameters of the a-hehx. A close examination of these regions often 

 makes it possible to identify a side-chain with certainty; in other cases 

 some ambiguity remains but the choice of side-chain can be reduced to 

 two or three. At the present resolution about one-third of the side-chains 

 can be identified with certainty, and another third with fairly high prob- 

 ability. It now becomes possible to correlate these X-ray results with the 

 preliminary data obtained by Dr. A. Edmundson who is engaged in 

 working out the amino acid sequence of myoglobin by chemical methods. 

 He has broken down the molecule into short peptides by tryptic digestion, 

 and has determined the composition, and in a few cases the internal 

 sequence, of these peptides. By comparing his results with our own it has 

 proved possible to place almost all the tryptic peptides along the polypep- 

 tide chain, and the order of peptides thus ascribed corresponds with the 

 order which has in a few cases been suggested by Edmundson on the basis 

 of a preliminary examination of the chymotryptic digest. A few discrepan- 

 cies remain, but although the amino acid sequence has not yet been com- 

 pletely determined, its main features are now beyond doubt. We are now 

 engaged in an attempt to increase the resolution of the X-ray results 

 still further, and we hope that the remaining ambiguities will then be 

 removed. 



Large molecules are often built up of sub-units, whose spatial arrange- 

 ment may be called the quaternary structure. At this level of organization 

 we return once more to simplicity and symmetry. Thus recent X-ray 

 studies of haemoglobin by Perutz and his collaborators [4], resulting in a 

 three-dimensional Fourier synthesis with a resolution of 5.5 A, have 

 shown that in this protein the four sub-units are arranged in the most 

 symmetrical manner possible, namely at the vertices of a tetrahedron. 

 Another very remarkable result has also emerged, namely that each of the 

 four sub-units, consisting of a single polypeptide chain together with a 

 haem group, very closely resembles the molecule of myoglobin in tertiary 

 structure. 



In still bigger molecules, such as the viruses, the number of sub- 

 units may be very large, nevertheless their arrangement is highly regular. 

 For example in tobacco mosaic virus there are about 2000 sub-units 

 arranged in the form of a helix ; in the spherical viruses the sub-units are 

 arranged on the surface of regular or semi-regular polyhedra. 



Thus we are now beginning to get a first glance at the general nature 

 of protein structure at all levels of complexity. It seems certain that 

 during the next 4 years these preliminary glimpses will lead to a detailed 

 picture of the structure of proteins which will give an immense impetus 

 to biochemistry generally, and indeed in many respects transform it. 



