Rapid inactivation of inhibitor () by elastase

Baumstark, John S.; Lee, Catherine Ting; Luby, Robert

doi:10.1016/0005-2744(77)90254-6

Cited by 45 publications

(14 citation statements)

References 16 publications

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“…The complexes than that described in these studies have weak appearance been reported previously (11,12). These complexes were seen with higher molar ratios of enzyme to in-K. Chan, University hibitor, and they may be formed by degradation of the higher molecular weight complexes by elastase mole-cules which were transiently diverted to the cleavage site which results in inactive alpha-l-antitrypsin.…”

Section: Resultssupporting

confidence: 55%

“…In previous work, we (11) and others (12) have re-ported that a number of complexes of different molecular weight form between alpha-l-antitrypsin and pancreatic elastase which can be demonstrated on polyacrylamide disc-gel electropherograms in sodium dodecyl sulfate (SDS-PAG).1 In the experiments reported herein, we describe conditions under which a complex was sufficiently stable to be isolated. The enzyme and inhibitor components were then separated from each other and characterized.…”

Section: Introductionmentioning

confidence: 85%

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Mechanism of Inhibition of Porcine Elastase by Human Alpha-1-Antitrypsin

James¹,

Cohen²

1978

J. Clin. Invest.

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A B S T R A C T The interaction of the human plasma protein, alpha-l-antitrypsin, with porcine pancreatic elastase was studied by isolating and characterizing their reaction products. Native alpha-l-antitrypsin has a mass ratio (Mr) of54,000, an amino-terminal glx, and a carboxy-terminal lys residue. The elastase used has an Mr-of 26,400 and an amino-terminal val residue. When the two proteins are combined at inhibitor excess, two major products resuilt. One of the products is a complex of the enzyme and inhibitor with amino-terminal ser and val residues, which indicates that a peptide has been removed from the amino-terminal end of the inhibitor. The second product is a modified form of alpha-l-antitrypsin with an Mr of 51,300, an aminoterminal glx residue and a carboxy-terminal thr-leu dipeptide. It has no inhibitory activity against elastase. The components of the isolated complex can be split at high pH in the presence of diisopropyl fluorophosphate, which results in a catalytically inactive enzyme with the same Mr and amino-terminal residue as the native enzyme, and a large fragment of alpha-lantitrypsin (alpha-l-antitrypsin*). This fragment has an Mr of 50,100, an amino-terminal ser residue and a carboxy-terminal thr-leu dipeptide. Based on these data, the following hypothesis is proposed. Elastase can attack alpha-l-antitrypsin at either oftwo major sites. If it attacks first at the carboxy side of the thr-leu dipeptide, located in the carboxy-terminal portion of the inhibitor, the alpha-l-antitrypsin is cleaved into two fragments with loss ofinhibitory activity and absence of complex formation. If, however, the elastase first attacks an x-ser bond near the amino-terminal end ofthe inhibitor, the elastase then reacts with alpha-iantitrypsin at the same leu moiety to form a stable complex with complete inhibition of the enzyme.

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Section: Resultssupporting

confidence: 55%

Section: Introductionmentioning

confidence: 85%

Mechanism of Inhibition of Porcine Elastase by Human Alpha-1-Antitrypsin

James¹,

Cohen²

1978

J. Clin. Invest.

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“…The detachment assay is thus a more sensitive measure of injury, since it detects both lethal, lytic injury and sublethal or nonlytic detachment. Catalase 100,ug/ml + SOD 20,ug/ml (36) 10.4+3.0…”

Section: Resultsmentioning

confidence: 99%

“…The subcellular location ofthe cell-detaching activity (36,37). Finally, neutral proteases bound to substrate on the endothelial cell surface might be temporarily protected from inactivation by a2-macroglobulin since the initial reaction of proteases with this inhibitor is competitive with respect to substrate (24).…”

Section: Resultsmentioning

confidence: 99%

Neutrophil-mediated endothelial injury in vitro mechanisms of cell detachment.

Harlan¹,

Killen²,

Harker³

et al. 1981

J. Clin. Invest.

412

152

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“…For this reason the investigation of oxidative [3,4] or proteolytic [5][6][7][8][9][10][11][12][13] inactivation of oq-PI by bacterial or human proteinases becomes an important feature in the regulation of elastic fiber turnover of the lung.…”

Section: Methodsmentioning

confidence: 99%

Inactivation of human plasma α₁‐proteinase inhibitor by human PMN leucocyte collagenase

1990

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Highly purified human polymorphonuclear leucocyte collagenase cleaved human e-l-proteinase inhibitor (~I-PI) at the carboxyl site of Phe asz (PT). The inhibitor was thereby rapidly inactivated and generated a primary degradation product as shown by reverse-phase HPLC and N-terminal sequencing. Prolonged incubation of the modified inhibitor with polymorphonuclear leucocyte collagenase led to the generation of a secondary degradation product with additional cleavage at the carboxyl site of Pro 3s7 (Pz).

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Rapid inactivation of inhibitor () by elastase

Cited by 45 publications

References 16 publications

Mechanism of Inhibition of Porcine Elastase by Human Alpha-1-Antitrypsin

Mechanism of Inhibition of Porcine Elastase by Human Alpha-1-Antitrypsin

Neutrophil-mediated endothelial injury in vitro mechanisms of cell detachment.

Inactivation of human plasma α₁‐proteinase inhibitor by human PMN leucocyte collagenase

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Rapid inactivation of inhibitor () by elastase

Cited by 45 publications

References 16 publications

Mechanism of Inhibition of Porcine Elastase by Human Alpha-1-Antitrypsin

Mechanism of Inhibition of Porcine Elastase by Human Alpha-1-Antitrypsin

Neutrophil-mediated endothelial injury in vitro mechanisms of cell detachment.

Inactivation of human plasma α1‐proteinase inhibitor by human PMN leucocyte collagenase

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Inactivation of human plasma α₁‐proteinase inhibitor by human PMN leucocyte collagenase