Oxidized Mucus Proteinase Inhibitor: a Fairly Potent Neutrophil Elastase Inhibitor

Overview

Journal Biochem J

Specialty Biochemistry

Date 1994 Oct 1

PMID 7945266

Citations 8

Authors

C Boudier

J G Bieth

Affiliations

Soon will be listed here.

Abstract

N-chlorosuccinimide oxidizes one of the methionine residues of mucus proteinase inhibitor with a second-order rate constant of 1.5 M-1.s-1. Cyanogen bromide cleavage and NH2-terminal sequencing show that the modified residue is methionine-73, the P'1 component of the inhibitor's active centre. Oxidation of the inhibitor decreases its neutrophil elastase inhibitory capacity but does not fully abolish it. The kinetic parameters describing the elastase-oxidized inhibitor interaction are: association rate constant kass. = 2.6 x 10(5) M-1.s-1, dissociation rate constant kdiss. = 2.9 x 10(-3) s-1 and equilibrium dissociation constant Ki = 1.1 x 10(-8) M. Comparison with the native inhibitor indicates that oxidation decreases kass. by a factor of 18.8 and increases kdiss. by a factor of 6.4, and therefore leads to a 120-fold increase in Ki. Yet, the oxidized inhibitor may still act as a potent elastase inhibitor in the upper respiratory tract where its concentration is 500-fold higher than Ki, i.e. where the elastase inhibition is pseudo-irreversible. Experiments in vitro with fibrous human lung elastin, the most important natural substrate of elastase, support this view: 1.35 microM elastase is fully inhibited by 5-6 microM oxidized inhibitor whether the enzyme-inhibitor complex is formed in the presence or absence of elastin and whether elastase is pre-adsorbed on elastin or not.

Citing Articles

Discrimination of Methionine Sulfoxide and Sulfone by Human Neutrophil Elastase.

Leahy D, Grant C, Jackson A, Duff A, Tardiota N, Van Haeften J Molecules. 2021; 26(17).

PMID: 34500777 PMC: 8434204. DOI: 10.3390/molecules26175344.

Sivelestat sodium hydrate inhibits neutrophil migration to the vessel wall and suppresses hepatic ischemia-reperfusion injury.

Sakai S, Tajima H, Miyashita T, Nakanuma S, Makino I, Hayashi H Dig Dis Sci. 2013; 59(4):787-94.

PMID: 24318803 DOI: 10.1007/s10620-013-2963-8.

Role of elastases in the pathogenesis of chronic obstructive pulmonary disease: implications for treatment.

Demkow U, Van Overveld F Eur J Med Res. 2010; 15 Suppl 2:27-35.

PMID: 21147616 PMC: 4360323. DOI: 10.1186/2047-783x-15-s2-27.

Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in human diseases.

Korkmaz B, Horwitz M, Jenne D, Gauthier F Pharmacol Rev. 2010; 62(4):726-59.

PMID: 21079042 PMC: 2993259. DOI: 10.1124/pr.110.002733.

Functional study of elafin cleaved by Pseudomonas aeruginosa metalloproteinases.

Guyot N, Bergsson G, Butler M, M Greene C, Weldon S, Kessler E Biol Chem. 2010; 391(6):705-16.

PMID: 20370321 PMC: 3396147. DOI: 10.1515/BC.2010.066.

References

Gast A, Anderson W, Probst A, Nick H, Thompson R, Eisenberg S . Pharmacokinetics and distribution of recombinant secretory leukocyte proteinase inhibitor in rats. Am Rev Respir Dis. 1990; 141(4 Pt 1):889-94. DOI: 10.1164/ajrccm/141.4_Pt_1.889. View

Matheson N, Wong P, Schuyler M, Travis J . Interaction of human alpha-1-proteinase inhibitor with neutrophil myeloperoxidase. Biochemistry. 1981; 20(2):331-6. DOI: 10.1021/bi00505a016. View

Eisenberg S, Hale K, Heimdal P, Thompson R . Location of the protease-inhibitory region of secretory leukocyte protease inhibitor. J Biol Chem. 1990; 265(14):7976-81. View

Rice W, Weiss S . Regulation of proteolysis at the neutrophil-substrate interface by secretory leukoprotease inhibitor. Science. 1990; 249(4965):178-81. DOI: 10.1126/science.2371565. View

Padrines M, Bieth J . Elastin decreases the efficiency of neutrophil elastase inhibitors. Am J Respir Cell Mol Biol. 1991; 4(2):187-93. DOI: 10.1165/ajrcmb/4.2.187. View

Vogelmeier C, Hubbard R, Fells G, Schnebli H, Thompson R, Fritz H . Anti-neutrophil elastase defense of the normal human respiratory epithelial surface provided by the secretory leukoprotease inhibitor. J Clin Invest. 1991; 87(2):482-8. PMC: 295108. DOI: 10.1172/JCI115021. View

Bohm B, Deutzmann R, Burkhardt H . Purification of a serine-proteinase inhibitor from human articular cartilage. Identity with the acid-stable proteinase inhibitor of mucous secretions. Biochem J. 1991; 274 ( Pt 1):269-73. PMC: 1149948. DOI: 10.1042/bj2740269. View

Rudolphus A, Kramps J, Dijkman J . Effect of human antileucoprotease on experimental emphysema. Eur Respir J. 1991; 4(1):31-9. View

Strandberg L, Lawrence D, Johansson L, Ny T . The oxidative inactivation of plasminogen activator inhibitor type 1 results from a conformational change in the molecule and does not require the involvement of the P1' methionine. J Biol Chem. 1991; 266(21):13852-8. View

10.

Boudier C, Holle C, Bieth J . Stimulation of the elastolytic activity of leukocyte elastase by leukocyte cathepsin G. J Biol Chem. 1981; 256(20):10256-8. View

11.

Gauthier F, Fryksmark U, Ohlsson K, Bieth J . Kinetics of the inhibition of leukocyte elastase by the bronchial inhibitor. Biochim Biophys Acta. 1982; 700(2):178-83. DOI: 10.1016/0167-4838(82)90095-4. View

12.

Tian W, Tsou C . Determination of the rate constant of enzyme modification by measuring the substrate reaction in the presence of the modifier. Biochemistry. 1982; 21(5):1028-32. DOI: 10.1021/bi00534a031. View

13.

Tournier J, Jacquot J, SADOUL P, Bieth J . Noncompetitive enzyme immunoassay for the measurement of bronchial inhibitor in biological fluids. Anal Biochem. 1983; 131(2):345-50. DOI: 10.1016/0003-2697(83)90181-1. View

14.

Ohlsson M, Rosengren M, Tegner H, Ohlsson K . Quantification of granulocyte elastase inhibitors in human mixed saliva and in pure parotid secretion. Hoppe Seylers Z Physiol Chem. 1983; 364(9):1323-8. DOI: 10.1515/bchm2.1983.364.2.1323. View

15.

POWERS J, Boone R, Carroll D, Gupton B, Kam C, Nishino N . Reaction of azapeptides with human leukocyte elastase and porcine pancreatic elastase. New inhibitors and active site titrants. J Biol Chem. 1984; 259(7):4288-94. View

16.

Kramps J, Franken C, Dijkman J . ELISA for quantitative measurement of low-molecular-weight bronchial protease inhibitor in human sputum. Am Rev Respir Dis. 1984; 129(6):959-63. DOI: 10.1164/arrd.1984.129.6.959. View

17.

Bieth J . In vivo significance of kinetic constants of protein proteinase inhibitors. Biochem Med. 1984; 32(3):387-97. DOI: 10.1016/0006-2944(84)90046-2. View

18.

Seemuller U, Arnhold M, Fritz H, Wiedenmann K, Machleidt W, Heinzel R . The acid-stable proteinase inhibitor of human mucous secretions (HUSI-I, antileukoprotease). Complete amino acid sequence as revealed by protein and cDNA sequencing and structural homology to whey proteins and Red Sea turtle proteinase inhibitor. FEBS Lett. 1986; 199(1):43-8. DOI: 10.1016/0014-5793(86)81220-0. View

19.

Thompson R, Ohlsson K . Isolation, properties, and complete amino acid sequence of human secretory leukocyte protease inhibitor, a potent inhibitor of leukocyte elastase. Proc Natl Acad Sci U S A. 1986; 83(18):6692-6. PMC: 386575. DOI: 10.1073/pnas.83.18.6692. View

20.

Stetler G, Brewer M, Thompson R . Isolation and sequence of a human gene encoding a potent inhibitor of leukocyte proteases. Nucleic Acids Res. 1986; 14(20):7883-96. PMC: 311822. DOI: 10.1093/nar/14.20.7883. View