Inactivation of protease inhibitors and lysozyme by hypochlorous acid: role of side-chain oxidation and protein unfolding in loss of biological function

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Inactivation of protease inhibitors and lysozyme by hypochlorous acid : role of side-chain oxidation and protein unfolding in loss of biological function. / Hawkins, Clare Louise; Davies, Michael Jonathan.

In: Chemical Research in Toxicology, Vol. 18, No. 10, 10.2005, p. 1600-10.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Hawkins, CL & Davies, MJ 2005, 'Inactivation of protease inhibitors and lysozyme by hypochlorous acid: role of side-chain oxidation and protein unfolding in loss of biological function', Chemical Research in Toxicology, vol. 18, no. 10, pp. 1600-10. https://doi.org/10.1021/tx050207b

APA

Hawkins, C. L., & Davies, M. J. (2005). Inactivation of protease inhibitors and lysozyme by hypochlorous acid: role of side-chain oxidation and protein unfolding in loss of biological function. Chemical Research in Toxicology, 18(10), 1600-10. https://doi.org/10.1021/tx050207b

Vancouver

Hawkins CL, Davies MJ. Inactivation of protease inhibitors and lysozyme by hypochlorous acid: role of side-chain oxidation and protein unfolding in loss of biological function. Chemical Research in Toxicology. 2005 Oct;18(10):1600-10. https://doi.org/10.1021/tx050207b

Author

Hawkins, Clare Louise ; Davies, Michael Jonathan. / Inactivation of protease inhibitors and lysozyme by hypochlorous acid : role of side-chain oxidation and protein unfolding in loss of biological function. In: Chemical Research in Toxicology. 2005 ; Vol. 18, No. 10. pp. 1600-10.

Bibtex

@article{d45068db5a68426288a6ac84c2906561,
title = "Inactivation of protease inhibitors and lysozyme by hypochlorous acid: role of side-chain oxidation and protein unfolding in loss of biological function",
abstract = "Excessive or misplaced activation of leukocytes causes host tissue damage which has been implicated in diseases such as atherosclerosis and chronic inflammation. This may arise via either the generation of oxidants such as hypochlorous acid (HOCl) by the heme enzyme myeloperoxidase, the action of released enzymes including lysozyme and proteases, or a combination of these two activities. Thus, oxidant-mediated inactivation of protease inhibitors that modulate tissue proteolysis by the released enzymes may exacerbate protease-induced degradation of host tissue. The role of myeloperoxidase-derived oxidants, such as HOCl, in the inactivation of Kunitz-type inhibitors and lysozyme is not well-characterized and is the subject of the current study. Exposure of both trypsin inhibitor and lysozyme to low molar excesses of HOCl compared to protein is shown to result in loss of function. With trypsin inhibitor, this loss of activity is associated with the selective oxidation of Trp, Tyr, and His residues, which results in protein unfolding and the disruption of complex formation with active trypsin. Oxidation of Met residues, a major target for HOCl, or the active site Arg, does not appear to play a key role in this loss of activity. In contrast, with lysozyme, oxidation of Met residues to Met sulfoxide appears to be the major process resulting in loss of enzyme activity. With both proteins, inactivation occurs in a time-dependent manner, consistent with both direct oxidation by HOCl and secondary reactions of protein chloramines formed from amine groups (e.g., from Lys and His) playing a role in loss of activity.",
keywords = "Animals, Chloramines, Enzyme Stability, Hypochlorous Acid, Muramidase, Oxidants, Oxidation-Reduction, Protease Inhibitors, Protein Conformation, Protein Denaturation, Protein Folding, Soybeans, Time Factors, Trypsin Inhibitors",
author = "Hawkins, {Clare Louise} and Davies, {Michael Jonathan}",
year = "2005",
month = "10",
doi = "10.1021/tx050207b",
language = "English",
volume = "18",
pages = "1600--10",
journal = "Chemical Research in Toxicology",
issn = "0893-228X",
publisher = "American Chemical Society",
number = "10",

}

RIS

TY - JOUR

T1 - Inactivation of protease inhibitors and lysozyme by hypochlorous acid

T2 - role of side-chain oxidation and protein unfolding in loss of biological function

AU - Hawkins, Clare Louise

AU - Davies, Michael Jonathan

PY - 2005/10

Y1 - 2005/10

N2 - Excessive or misplaced activation of leukocytes causes host tissue damage which has been implicated in diseases such as atherosclerosis and chronic inflammation. This may arise via either the generation of oxidants such as hypochlorous acid (HOCl) by the heme enzyme myeloperoxidase, the action of released enzymes including lysozyme and proteases, or a combination of these two activities. Thus, oxidant-mediated inactivation of protease inhibitors that modulate tissue proteolysis by the released enzymes may exacerbate protease-induced degradation of host tissue. The role of myeloperoxidase-derived oxidants, such as HOCl, in the inactivation of Kunitz-type inhibitors and lysozyme is not well-characterized and is the subject of the current study. Exposure of both trypsin inhibitor and lysozyme to low molar excesses of HOCl compared to protein is shown to result in loss of function. With trypsin inhibitor, this loss of activity is associated with the selective oxidation of Trp, Tyr, and His residues, which results in protein unfolding and the disruption of complex formation with active trypsin. Oxidation of Met residues, a major target for HOCl, or the active site Arg, does not appear to play a key role in this loss of activity. In contrast, with lysozyme, oxidation of Met residues to Met sulfoxide appears to be the major process resulting in loss of enzyme activity. With both proteins, inactivation occurs in a time-dependent manner, consistent with both direct oxidation by HOCl and secondary reactions of protein chloramines formed from amine groups (e.g., from Lys and His) playing a role in loss of activity.

AB - Excessive or misplaced activation of leukocytes causes host tissue damage which has been implicated in diseases such as atherosclerosis and chronic inflammation. This may arise via either the generation of oxidants such as hypochlorous acid (HOCl) by the heme enzyme myeloperoxidase, the action of released enzymes including lysozyme and proteases, or a combination of these two activities. Thus, oxidant-mediated inactivation of protease inhibitors that modulate tissue proteolysis by the released enzymes may exacerbate protease-induced degradation of host tissue. The role of myeloperoxidase-derived oxidants, such as HOCl, in the inactivation of Kunitz-type inhibitors and lysozyme is not well-characterized and is the subject of the current study. Exposure of both trypsin inhibitor and lysozyme to low molar excesses of HOCl compared to protein is shown to result in loss of function. With trypsin inhibitor, this loss of activity is associated with the selective oxidation of Trp, Tyr, and His residues, which results in protein unfolding and the disruption of complex formation with active trypsin. Oxidation of Met residues, a major target for HOCl, or the active site Arg, does not appear to play a key role in this loss of activity. In contrast, with lysozyme, oxidation of Met residues to Met sulfoxide appears to be the major process resulting in loss of enzyme activity. With both proteins, inactivation occurs in a time-dependent manner, consistent with both direct oxidation by HOCl and secondary reactions of protein chloramines formed from amine groups (e.g., from Lys and His) playing a role in loss of activity.

KW - Animals

KW - Chloramines

KW - Enzyme Stability

KW - Hypochlorous Acid

KW - Muramidase

KW - Oxidants

KW - Oxidation-Reduction

KW - Protease Inhibitors

KW - Protein Conformation

KW - Protein Denaturation

KW - Protein Folding

KW - Soybeans

KW - Time Factors

KW - Trypsin Inhibitors

U2 - 10.1021/tx050207b

DO - 10.1021/tx050207b

M3 - Journal article

VL - 18

SP - 1600

EP - 1610

JO - Chemical Research in Toxicology

JF - Chemical Research in Toxicology

SN - 0893-228X

IS - 10

ER -

ID: 129671613