THE STRUfTURE OF GLOBULAR PROTEINS 9 



References 



Pauling, L., Corey, R. B., and Branson, H. R., Proc. iiat. Acad. Sci., Wash. 



37, 205 (1951). 



Bodo, G., Dintzis, H. M., Kendrew, J. C, and WyckofF, H. W., Proc. row Soc. 



A 253, 70 (1959)- 



Kendrew, J. C, Dickerson, R. E., Strandberg, B. E., Hart, R. G., Davies, D. R., 



Phillips, D. C, and Shore, V. C, Nature, Loud. 185, 422 (i960). 



Perutz, M. F., Rossmann, M. G., Cullis, A. P., Muirhead, H., Will, G., and 



North, A. C. T., Nature, Land. 185, 416 (i960). 



Discussion 



TisELius : Is it possible by comparing the structure, derived by your crystallo- 

 graphic methods, of reduced and oxidized haemoglobin or myoglobin to get any 

 hints about any structural changes which would accompany the combination with 

 oxygen ? 



Kendrew : A crystal of met-myoglobin can very easily be converted into the 

 reduced form by diffusing into it a solution of sodium dithionite and watching the 

 colour change. The crystal is quite unharmed by this procedure, and its X-ray 

 pattern is virtually identical with that of met-myoglobin. If the same experiment is 

 performed with haemoglobin, the result is quite different; haemoglobin crystals 

 on reduction fall to pieces, and if one begins with a solution of reduced haemoglobin 

 and adds salt the crystals which are formed are quite different from those of met- 

 haemoglobin. The simplest hypothesis which would explain these results is that 

 during oxygenation the haemoglobin molecule changes shape, the sub-units moving 

 relative to one another : in myoglobin no such change could occur because there are 

 no sub-units. This idea is purely speculative at present, but my colleague Dr. 

 Perutz is now beginning a study of crystals of reduced haemoglobin with the object 

 of discovering exactly what differences there are between its structure and that of 

 met-haemoglobin. 



Chan'CE: It is obvious that Dr. Kendrew "s results are important not only for 

 those interested in the mechanism of oxygenation but also for those interested in 

 the mechanism of haemoprotein action where the histidine group connected to the 

 iron is of special importance. I have one question which is prompted by Philip 

 George, as to how certain one may be that this link is histidine ; how well does 

 histidine fit the electron densities near the iron atom ? A second question is the 

 interesting electron-dense material on the other side of the water molecule, which 

 leads one to wonder in the reactions of the ferrimyoglobin which is really what we 

 are talking about, the way which you would speculate that this material will inter- 

 fere with ligands for the oxygen atom ? 



Kendrew: At the present resolution of our Fourier synthesis of myoglobin, 

 namely 2 A, it is not possible to be absolutely certain of the identity of the haem- 

 linked side chain in myoglobin, but it is very probably histidine. As an alternative 

 we have tried to build a model of lysine into the electron density, but for several 

 reasons this solution seems very unsatisfactory. 



With regard to the group on the other side of the haem group, we are in more 

 difficulty. We think it probable that this residue also is histidine, but there is a 



