The primary structure of human urogastrone.
Urogastrone is a potent inhibitor of gastric acid secretion which is present in human urine. Its existence has been known for over 30 years but it has only recently been isolated in a sufficiently pure form for detailed structural studies to be undertaken. Two separate polypeptides beta- and gamma-urogastrone were isolated. The structures were established by carrying out enzymic degradations of S-carboxymethyl and S-carboxamidomethyl derivatives with trypsin, chymotrypsin, thermolysin and a protease derived from the fungus Armillaria mellea. Sequences of the smaller peptides thus obtained were determined by the dansyl Edman method. Partial acid hydrolysis of urogastrone itself gave fragments containing single intact disulphide bonds, and oxidation then allowed the direction of individual bonds to be established. Beta-Urogastrone was shown to be a 53-amino acid residue polypeptide containing three disulphide bonds, and gamma-urogastrone had an identical sequence but lacked the C-terminal arginine residue. Urogastrone was subsequently found to be structurally related to mouse epidermal growth factor in that 37 of the 53 residues were commonly located in each polypeptide. Furthermore, as both peptides has similar effects upon gastric acid secretion and upon epidermal growth, urogastrone was also a human epidermal growth factor. The 16 variable residues were spread across the molecule, all apart from two were compatible with single base changes in the triplet condons, and the overall effect was to make uorgastrone more acidic than EGF. The smallest biologically active unit has not been defined but at least six residues can be removed from the C-terminus without causing a reduction in potency.
D000595:Amino Acid Sequence; D055598:Chemical Phenomena; D002621:Chemistry; D002918:Chymotrypsin; D004220:Disulfides; D004815:Epidermal Growth Factor / Q000302:isolation & purification / Q000502:physiology; D005768:Gastrointestinal Hormones / Q000502:physiology; D006801:Humans; D006868:Hydrolysis; D010084:Oxidation-Reduction; D010447:Peptide Hydrolases; D013820:Thermolysin; D014357:Trypsin
D004220:Disulfides; D005768:Gastrointestinal Hormones; D004815:Epidermal Growth Factor; D010447:Peptide Hydrolases; D002918:Chymotrypsin; D014357:Trypsin; D013820:Thermolysin