PROTEIN STRUCTURE 



deduced by Sanger to be present in the original peptide chains 

 of insuhn. However, the complete and careful amino acid 

 analyses by Harfenist (46) on these insulins are in full accord 

 with the values to be expected from the structural formulas of 

 Sanger and his associates. The fitting together of a great mass 

 of circumstantial evidence leaves little doubt of the general 

 correctness of the inferred sequences. The great difficulties 

 that attended the determination of the positions of the disulfide 

 linkages, due to the ease of disulfide interchange reactions, appear 



CHj-S— S-CHj 



I 7 I 30_ 



s s 



\ f 



CHj CH2 ^^^^ 



^^ I 7 19 30 



Fig. 1 . Outline of the structure of beef, hog, and sheep insulins. 

 The glycyl (A) chain, with 21 residues, and the phenylalanyl (B) 

 chain, with 30 residues, both have the same orientation, with the free 

 terminal a-amino groups at the left-hand side of the diagram. The 

 sequence of residues 3 to 14 inclusive of the A chain is shown in more 

 detail in Figure 2, and the complete sequences in both chains are given 

 in the text. Possible configurations of the insulin molecule in space are 

 discussed later. 



to have been overcome, with decisive evidence in favor of the 

 cross linkage of the A and B chains at two points, the third disul- 

 fide linkage serving to bridge residues 6 and 11 of the A chain 

 (21,91a,91b,93). The final proof of structure by synthesis in 

 the laboratory may still be a long way off", but the greatness of 

 the achievement is not thereby diminished. 



The outline of the inferred structure of the insulins is given 

 in Figure 1, and the sequences in the A and B chains are given 

 in detail below. It is remarkable that the complete sequence of 

 amino acid residues in the B chain is identical for all three 

 species of insulin; the same is true in the A chain except for 

 residues 8, 9, and 10, which lie within the intrachain disulfide 



379 



