Compared action of neutrophil proteinase 3 and elastase on model substrates. Favorable effect of S'-P' interactions on proteinase 3 catalysts.
Neutrophil proteinase 3 (Pr3) and elastase (NE) may cause lung tissue destruction in emphysema and cystic fibrosis. These serine proteinases have similar P(1) specificities. We have compared their catalytic activity using acyl-tetrapeptide-p-nitroanilides, which occupy the S(5)-S'(1) subsites of their substrate binding site, and intramolecularly quenched fluorogenic heptapeptides, which bind at S(5)-S'(4). Most p-nitroanilide substrates are turned over slowly by Pr3 as compared with NE. These differences disappear with the fluorogenic heptapeptides, some of which are hydrolyzed even faster by Pr3 than by NE. Elongation of substrates strongly increases the catalytic efficiency of Pr3, whereas it has little effect on NE catalysis. These different sensitivities to S'-P' interactions show that Pr3 and NE are not interchangeable enzymes despite their similar P(1) specificity.
Koehl
Catherine
C
Laboratoire d'Enzymologie, INSERM U392, Université Louis Pasteur de Strasbourg, 67400 Illkirch, France.
Knight
C Graham
CG
Bieth
Joseph G
JG
D000595:Amino Acid Sequence; D002384:Catalysis; D014890:Granulomatosis with Polyangiitis; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D019272:Leukocyte Elastase / Q000378:metabolism*; D053146:Myeloblastin; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D013379:Substrate Specificity
D009842:Oligopeptides; D012697:Serine Endopeptidases; D019272:Leukocyte Elastase; D053146:Myeloblastin