Peptides, methionine, binding

Methionine 13 in S-peptide has been modified by oxidation to the sul-fone or by conversion to a sulfonium salt with either iodoacetic acid or iodoacetamide (138). There is a dramatic lowering of the peptide-protein binding constant for all of the derivatives, but the complexes when formed appear to have nearly normal catalytic activity. The X-ray structure does not appear to permit the normal sulfur location with the sulfonium salts. Sterically, Met 13 can be moved by rotation about the carbon a-carbon / bond so that the residue sticks out into the solvent. This can be done without any major change in the conformation of the rest of the peptide. Thus the active site could be maintained undisturbed while the contribution of Met 13 to the S-peptide S-protein association would be lacking. 

Fig. 13. The binding sites of calcium in (a) parvalbumin (41a), (b) annexin (41) and (c) calmodulin (42). The drawings show two bidentate carboxylates coordinated to Ca2 in the EF-hand site of parvalbumin, and one bidentate carboxylate coordinated to Ca2 in annexin and calmodulin. All the donor atoms coordinated to the calciums are oxygen donor atoms from carboxylates of asp = aspartate, or glu = glutamate, or else peptide carbonyl oxygens from gly = glycine or met = methionine. Redrawn after Refs. (41-42).

Fragments of the peptide hormone p-lipotropin have been found to show similar binding to opiate receptors. These molecules, the endorphins, show profound CNS activity in experimental animals. It is of interest that one of these, p-endorphin, incorporates in its chain the exact sequence of amino acids that constitutes methionine enkaphalin. 

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