Structural requirements for nucleophilic substrates of carboxypeptidase Y.
The composition and structural aspects of the amino and carboxylic acid groups required for incorporation into peptides by transpeptidation and inhibition of hydrolysis in carboxypeptidase Y-catalyzed reactions were studied. Separation of these two groups by even one carbon prevents incorporation by transpeptidation and does not inhibit incorporation of other amino acids into model peptides. Substitution of phosphonic or sulfonic acids for the carboxylic acid group also results in loss of incorporation by transpeptidation. Only the sulfonic acid analog of glycine causes inhibition of hydrolysis and this inhibition is lost when serine is included in the reaction. d-Serine is not incorporated by carboxypeptidase Y, and its presence in the reaction mixture does not inhibit the incorporation of the L-isomer.
Department of Chemistry, University of Nebraska-Lincoln 68588-0304.
W S
WS
Lewis
S M
SM
Schuster
D002268:Carboxypeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006868:Hydrolysis; D066298:In Vitro Techniques; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D063065:Organophosphonates / Q000494:pharmacology; D010458:Peptidyl Transferases / Q000378:metabolism; D012694:Serine / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013451:Sulfonic Acids / Q000494:pharmacology; D015091:beta-Alanine / Q000494:pharmacology
D009842:Oligopeptides; D063065:Organophosphonates; D013451:Sulfonic Acids; D015091:beta-Alanine; D012694:Serine; D010458:Peptidyl Transferases; D002268:Carboxypeptidases; C022633:serine carboxypeptidase; C045904:aminomethanesulfonic acid