BARBARA W. LOW AND JOHN T. EDSALL 



the problem of protein structure is not still largely an enigma. 

 Detailed x-ray diffraction studies of protein crystals may one 

 day succeed in the determination of a detailed molecular 

 structure for some protein. The probable absence of regions 

 of ordered side-chain array — ordered, that is, in the crystalline 

 sense — makes it difficult to attack the remaining problems of 

 three-dimensional structure systematically. Scale models may 

 be helpful even though at this stage they are unfortunately not 

 able to indicate more than the stereochemical plausibility of a 

 trial structure. Electrostatic forces, van der Waals interactions, 

 and lyophobic effects, etc., cannot be or have not yet been built 

 into scale models. The models will not automatically fall into 

 place and throw the structure into its proper form. The kind 

 of information that such investigations do provide is illustrated 

 by the model studies of insulin based on the Sanger sequences 

 discussed below. 



Insulin 



The insulin molecule contains one A and one B chain (as 

 described on page 379), the molecular weight being 5734 for 

 beef insulin. The molecules associate in aqueous solution. At 

 /?H values of 2 to 3 the predominating species is a dimer of two 

 molecules. This 12,000 molecular weight unit is usually referred 

 to as the monomer solution unit since it has not been found 

 possible to dissociate insulin further in aqueous solution except 

 under special and unusual conditions (58). At higher j&H values 

 further association occurs and around j&H 6 to 7 a trimer unit 

 of molecular weight 36,000 predominates. 



At /)H 6 to 7 the insulin trimer unit of molecular weight 

 36,000 crystallizes from zinc-containing solutions (99). The 

 amount of zinc incorporated into the crystal may vary over a 

 wide range (25) and may be considerably less than 3 zinc atoms 

 per 36,000 unit. In zinc-free solutions at j&H 2.5 to 3.5 insulin 

 may be crystallized as the sulfate (63), selenate, citrate, or 

 formate. The unit of packing in the orthorhombic crystals of 

 acid insulin sulfate is the solution monomer containing 2 (A and 



420 



