BARBARA W. LOW AND JOHN T. EDSALL 



combine quite firmly with two, and only two, mercury atoms. 

 Evidently each mercury forms a bond between a pair of sulf- 

 hydryl groups, by a reaction similar to that which occurs in 

 serum mercaptalbumin when two mercaptalbumin molecules 

 are linked through their sulfhydryl groups by a mercury atom 

 (36,39,50). Hence these sulfhydryl groups of hemoglobin must 

 exist in pairs, the members of each pair being very close to- 

 gether. The x-ray work of Bragg and Perutz (18) on these 

 mercurial derivatives, which give crystals isomorphous with 

 those of the original hemoglobin, indicates that the two pairs of 

 sulfhydryl groups are arranged symmetrically around the two- 

 fold axis of the hemoglobin molecule. In addition to these four 

 sulfhydryl groups, which are titratable with silver ions in the 

 native hemoglobin, two more become titratable when the hemo- 

 globin is denatured; Ingram has produced evidence that these 

 two additional groups are geometrically closely associated with 

 the other pairs, so that there are in effect two clusters of sulf- 

 hydryls in the hemoglobin molecule, each consisting of three 

 — SH groups. These groups, therefore, are not distributed at 

 random in the molecule but are closely concentrated within 

 two very narrow regions. There is of course as yet no evidence 

 that these sets of associated groups are members of the same 

 peptide chain; they may be in different chains, but packed 

 close together for geometrical reasons. Nevertheless this is a 

 striking example of the clustering together of like groups within 

 certain very limited portions of a large and complex molecule. 



It is tempting to say that the presence of adjoining sets of 

 similar residues in the sequences of peptide chains was to be 

 expected — that protein molecules are built to do a job, and that 

 the doing of that job requires the concentration of certain sets of 

 side-chain groups — charged groups, or hydroxyl groups, or 

 perhaps nonpolar groups — within a relatively limited region. 

 Probably there is more than a germ of truth in this conception, 

 but the idea as naively stated here is certainly too simple. The 

 order of residues in the sequence of a peptide chain does not in 

 itself specify their spatial relations. If, for example, the chain is 



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