Thioester hydrolysis by matrix metalloproteinases.
Substrate specificity studies from this laboratory suggested that Ac-Pro-Leu-Ala-Nva-TrpNH2, and its thioester derivative, Ac-Pro-Leu-Ala-SNva-TrpNH2, would be substrates for stromelysin (SLN). In this paper, we report that both peptides are efficiently hydrolyzed not only by SLN but also by two other matrix metalloproteinases, collagenase and gelatinase, and by the bacterial metalloproteinase thermolysin. The pH-dependence of kc/Km for the SLN-catalyzed hydrolysis of Ac-Pro-Leu-Ala-SNva-TrpNH2 is identical to pH-dependencies for peptide hydrolysis and suggests no major mechanistic differences between thioester and amide hydrolysis by SLN.
Stein
R L
RL
Department of Enzymology, Merck Research Laboratories, Rahway, New Jersey 07065.
Izquierdo-Martin
M
M
D000595:Amino Acid Sequence; D003013:Clostridium / Q000201:enzymology; D017364:Collagenases / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008433:Mathematics; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000378:metabolism*; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013820:Thermolysin / Q000378:metabolism
D009842:Oligopeptides; D011994:Recombinant Proteins; D013438:Sulfhydryl Compounds; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D013820:Thermolysin