PROTEIN STRUCTURE 



To interpret such patterns will be a formidable task in 

 which as yet almost no progress has been made. The observed 

 sequences appear to be compatible with the view that any one 

 of the amino acid residues may be placed next to any other, in 

 substances which nature is capable of producing. However, 

 some of the observed sequences suggest that similar or identical 

 side-chain residues appear to be bunched together more fre- 

 quently than would be expected on a random basis. Perhaps 

 significant, for instance, is the aromatic side-chain sequence 

 Phe.Phe.Tyr. in residues 24-26 of theB chain of insulin. The 

 presence of three alanine residues and one valine in the hexa- 

 peptide derived from ovalbumin represents a striking predomi- 

 nance of nonpolar side chains in this short series. Three hydroxy- 

 amino acid residues — two aliphatic and one aromatic — appear at 

 the iV- terminal end of the chain of jS-corticotropin. The 

 sequence Lys.Lys.Arg.Arg, containing four successive positively 

 charged side chains, occurs in residues 15-18 of this substance. 

 Indeed all the nine positively charged groups in /^-corticotropin, 

 including the iV-terminal ammonium group of serine, are located 

 between positions 1 and 21 ; all but one of the seven negatively 

 charged groups, including the C- terminal phenylalanine, lie 

 between positions 25 and 39. The molecule may thus be 

 considered as consisting of a positively charged segment in one 

 half, and a negatively charged segment in the other. Biological 

 studies show that the former — including also the hydroxyl side 

 chains on residues 1, 2, and 3 — is essential to hormone activity; 

 the latter, at least the last 1 5 residues, is nonessential. 



Finally we may mention evidence on a rather different 

 level — the distribution of sulfhydryl groups in horse hemoglobin. 

 The importance of these groups for the oxygen affinity of hemo- 

 globin was first shown by the work of Riggs (89). Binding of 

 the sulfhydryls by a mercurial modifies both the oxygen affinity 

 and the heme-heme interactions, and the effects are reversible 

 on removing the mercurial. Ingram (51) has recently shown in 

 a careful study that four sulfhydryl groups are readily titrated 

 with silver ions in the native hemoglobin; however, these four 



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