Methionine oxidation in human growth hormone and human chorionic somatomammotropin. Effects on receptor binding and biological activities.
The oxidation of the methionine residues of human growth hormone (hGH) and human chorionic somatomammotropin (hCS) to methionine sulfoxide by hydrogen peroxide has been studied. The kinetics of oxidation of individual methionine residues has been measured by reverse-phase high pressure liquid chromatography tryptic peptide mapping. Met-170 is completely resistant to oxidation in both hormones. The other 3 methionine residues in hCS (Met-64, Met-96, and Met-179) have markedly different reaction rates. Oxidation of the methionine residues does not appear to cause gross conformational changes in either hGH or hCS, as judged by CD and 1H NMR spectroscopy. Oxidation of Met-14 and Met-125 in hGH has little effect on affinity of the hormone for lactogenic receptors or on its potency in the Nb2 rat lymphoma in vitro bioassay for lactogenic hormones. The oxidation of Met-64 and/or Met-179 in hCS reduces profoundly both its affinity for lactogenic receptors and its in vitro biological potency. It is inferred by induction that residues 64 and/or 179 are critical for the binding of both hGH and hCS to lactogenic receptors and the expression of lactogenic biological activity.
D000818:Animals; D002460:Cell Line; D005260:Female; D013006:Growth Hormone / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide; D008223:Lymphoma; D008321:Mammary Glands, Animal / Q000378:metabolism; D008715:Methionine / Q000031:analogs & derivatives; D051379:Mice; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000032:analysis; D010449:Peptide Mapping; D010928:Placental Lactogen / Q000378:metabolism* / Q000494:pharmacology; D011487:Protein Conformation; D018000:Receptors, Peptide; D011981:Receptors, Prolactin / Q000378:metabolism*; D011986:Receptors, Somatotropin / Q000378:metabolism*
D010446:Peptide Fragments; D018000:Receptors, Peptide; D011981:Receptors, Prolactin; D011986:Receptors, Somatotropin; C028202:placental lactogen receptor; D013006:Growth Hormone; D010928:Placental Lactogen; D008715:Methionine; D006861:Hydrogen Peroxide; C013111:methionine sulfoxide