Influence of the carboxyl terminus of luteinizing hormone-releasing hormone and bradykinin on hydrolysis by brain endo-oligopeptidases.
A homogeneous preparation of endo-oligopeptidase A from rabbit brain cleaves luteinizing hormone-releasing hormone (less than Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) at the Tyr-Gly bond only after the removal of Gly-NH2 from the COOH-terminal position of the molecule. The influence of the carboxyl terminus on hydrolysis by brain endo-oligopeptidases was studied using bradykinin as a model substrate. The substitution of the carboxyl group of bradykinin by the amide reduces by 2.5-fold the rate of Phe-Ser bond hydrolysis by endo-oligopeptidase A but has no effect on the rate of hydrolysis of the Pro-Phe bond by endo-oligopeptidase B. On the other hand, the deletion of Phe-Arg from the COOH-terminal portion of bradykinin makes the peptide resistant to hydrolysis by endo-oligopeptidase A whereas it increases by 5-fold the rate of hydrolysis of the Pro-Gly bond by endo-oligopeptidase B.
D000595:Amino Acid Sequence; D000818:Animals; D001920:Bradykinin / Q000378:metabolism*; D001921:Brain / Q000201:enzymology; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006868:Hydrolysis; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011817:Rabbits; D013379:Substrate Specificity
D007987:Gonadotropin-Releasing Hormone; D010450:Endopeptidases; D007703:Peptidyl-Dipeptidase A; D003546:Cysteine Endopeptidases; C028307:endopeptidase B; D001920:Bradykinin