Crystallographic studies of myoglobin 



J. C. KENDREW 



Medical Research Council Unit for Molecular Biology, 

 Cavendish Laboratory, University of Cambridge 



This paper is an outline of recent developments in X-ray studies of the 

 structure of myoglobin. These studies have been undertaken in our labora- 

 tory and in the Royal Institution at London with a number of colleagues, 

 past and present, including M. M. Bluhm, G. Bodo, H. M. Dintzis, V. M. 

 Ingram, J. Kraut, R. G. Parrish, P. J. Pauling, D. C, Phillips, Mary Pinkerton, 

 Helen Scouloudi, and H. Wyckoff. Several similar projects are under way 

 in other laboratories, all having the object of determining the structure of 

 a globular protein purely by X-ray methods; they are concerned with a 

 variety of proteins, notably haemoglobin, insulin, and ribonuclease. Although 

 the methods they use, and the stage they have reached, vary from project 

 to project, the myoglobin programme may be taken as typical of them all. 

 Until four years ago no one knew, even in principle, how structures as com- 

 plex as proteins could be solved; but Perutz's successful application of the 

 so-called method of isomorphous replacement to haemoglobin^ resolved a 

 deadlock in the subject by indicating a secure, though difficult, line of ad- 

 vance. Since then the potentialities of this method in protein crystallography 

 have been explored, and it has been used to obtain several two-dimensional 

 electron density projections of protein crystals (haemoglobin of horse- and 

 ox;^ myoglobin of sperm whale"* and seal;^ ribonuclease).^-'^ Gradually it 

 has become clear that the only way of exploiting the new method usefully 

 is to extend it to three dimensions : for a three-dimensional electron density 

 map, whatever its limitations as to resolution and accuracy, would at least 

 completely avoid the overlapping of atoms which makes projections of com- 

 plex structures (including all those just enumerated) impossible to inter- 

 pret. In most of the crystalline protein projects the possibility of extending 

 the analysis to three dimensions is being explored at the present time. This 

 paper will show that at any rate in myoglobin such extension is possible in 

 principle, although we have not yet collected all the necessary experimental 

 data, nor are we yet certain what resolving power will be needed to reveal 

 recognizable features of the structure. 



