Site-specific hypochlorous acid-induced oxidation of recombinant human myoglobin affects specific amino acid residues and the rate of cytochrome b5-mediated heme reduction

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Site-specific hypochlorous acid-induced oxidation of recombinant human myoglobin affects specific amino acid residues and the rate of cytochrome b5-mediated heme reduction. / Szuchman-Sapir, Andrea J; Pattison, David I; Davies, Michael Jonathan; Witting, Paul K.

In: Free Radical Biology & Medicine, Vol. 48, No. 1, 01.01.2010, p. 35-46.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Szuchman-Sapir, AJ, Pattison, DI, Davies, MJ & Witting, PK 2010, 'Site-specific hypochlorous acid-induced oxidation of recombinant human myoglobin affects specific amino acid residues and the rate of cytochrome b5-mediated heme reduction', Free Radical Biology & Medicine, vol. 48, no. 1, pp. 35-46. https://doi.org/10.1016/j.freeradbiomed.2009.09.023

APA

Szuchman-Sapir, A. J., Pattison, D. I., Davies, M. J., & Witting, P. K. (2010). Site-specific hypochlorous acid-induced oxidation of recombinant human myoglobin affects specific amino acid residues and the rate of cytochrome b5-mediated heme reduction. Free Radical Biology & Medicine, 48(1), 35-46. https://doi.org/10.1016/j.freeradbiomed.2009.09.023

Vancouver

Szuchman-Sapir AJ, Pattison DI, Davies MJ, Witting PK. Site-specific hypochlorous acid-induced oxidation of recombinant human myoglobin affects specific amino acid residues and the rate of cytochrome b5-mediated heme reduction. Free Radical Biology & Medicine. 2010 Jan 1;48(1):35-46. https://doi.org/10.1016/j.freeradbiomed.2009.09.023

Author

Szuchman-Sapir, Andrea J ; Pattison, David I ; Davies, Michael Jonathan ; Witting, Paul K. / Site-specific hypochlorous acid-induced oxidation of recombinant human myoglobin affects specific amino acid residues and the rate of cytochrome b5-mediated heme reduction. In: Free Radical Biology & Medicine. 2010 ; Vol. 48, No. 1. pp. 35-46.

Bibtex

@article{dbac6b7592de446f9cb15b21008db1de,
title = "Site-specific hypochlorous acid-induced oxidation of recombinant human myoglobin affects specific amino acid residues and the rate of cytochrome b5-mediated heme reduction",
abstract = "Myeloperoxidase catalyzes the reaction of chloride ions with H(2)O(2) to yield hypochlorous acid (HOCl), which can damage proteins. Human myoglobin (HMb) differs from other Mbs by the presence of a cysteine residue at position 110 (Cys110). This study has (i) compared wild-type and a Cys110Ala variant of HMb to assess the influence of Cys110 on HOCl-induced amino acid modification and (ii) determined whether HOCl oxidation of HMb affects the rate of ferric heme reduction by cytochrome b(5). For wild-type HMb (HOCl:Mb ratio of 5:1 mol:mol), Cys110 was preferentially oxidized to a homodimeric or cysteic acid product-sulfenic/sulfinic acids were not detected. At a HOCl:Mb ratio 10:1 mol:mol, methionine (Met) oxidation was detected, and this was enhanced in the Cys110Ala variant. Tryptophan (Trp) oxidation was detected only in the Cys110Ala variant at the highest HOCl dose tested, with oxidation susceptibility following the order Cys>Met>Trp. Tyrosine chlorination was evident only in reactions between HOCl and the Cys110Ala variant and at a longer incubation time (24 h), consistent with the formation via chlorine-transfer reactions from preformed chloramines. HOCl-mediated oxidation of wild-type HMb resulted in a dose-dependent decrease in the observed rate constant for ferric heme reduction (approx two-fold at HOCl:Mb of 10:1 mol:mol). These data indicate that Cys110 influences the oxidation of HMb by HOCl and that oxidation of Cys, Met, and Trp residues is associated with a decrease in the one-electron reduction of ferric HMb by other proteins; such heme-Fe(3+) reduction is critical to the maintenance of function as an oxygen storage protein in tissues.",
keywords = "Amino Acids, Cytochromes b5, Heme, Humans, Hypochlorous Acid, Iron, Myoglobin, Oxidation-Reduction, Recombinant Proteins",
author = "Szuchman-Sapir, {Andrea J} and Pattison, {David I} and Davies, {Michael Jonathan} and Witting, {Paul K}",
note = "Crown Copyright 2009. Published by Elsevier Inc. All rights reserved.",
year = "2010",
month = "1",
day = "1",
doi = "10.1016/j.freeradbiomed.2009.09.023",
language = "English",
volume = "48",
pages = "35--46",
journal = "Free Radical Biology & Medicine",
issn = "0891-5849",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - Site-specific hypochlorous acid-induced oxidation of recombinant human myoglobin affects specific amino acid residues and the rate of cytochrome b5-mediated heme reduction

AU - Szuchman-Sapir, Andrea J

AU - Pattison, David I

AU - Davies, Michael Jonathan

AU - Witting, Paul K

N1 - Crown Copyright 2009. Published by Elsevier Inc. All rights reserved.

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Myeloperoxidase catalyzes the reaction of chloride ions with H(2)O(2) to yield hypochlorous acid (HOCl), which can damage proteins. Human myoglobin (HMb) differs from other Mbs by the presence of a cysteine residue at position 110 (Cys110). This study has (i) compared wild-type and a Cys110Ala variant of HMb to assess the influence of Cys110 on HOCl-induced amino acid modification and (ii) determined whether HOCl oxidation of HMb affects the rate of ferric heme reduction by cytochrome b(5). For wild-type HMb (HOCl:Mb ratio of 5:1 mol:mol), Cys110 was preferentially oxidized to a homodimeric or cysteic acid product-sulfenic/sulfinic acids were not detected. At a HOCl:Mb ratio 10:1 mol:mol, methionine (Met) oxidation was detected, and this was enhanced in the Cys110Ala variant. Tryptophan (Trp) oxidation was detected only in the Cys110Ala variant at the highest HOCl dose tested, with oxidation susceptibility following the order Cys>Met>Trp. Tyrosine chlorination was evident only in reactions between HOCl and the Cys110Ala variant and at a longer incubation time (24 h), consistent with the formation via chlorine-transfer reactions from preformed chloramines. HOCl-mediated oxidation of wild-type HMb resulted in a dose-dependent decrease in the observed rate constant for ferric heme reduction (approx two-fold at HOCl:Mb of 10:1 mol:mol). These data indicate that Cys110 influences the oxidation of HMb by HOCl and that oxidation of Cys, Met, and Trp residues is associated with a decrease in the one-electron reduction of ferric HMb by other proteins; such heme-Fe(3+) reduction is critical to the maintenance of function as an oxygen storage protein in tissues.

AB - Myeloperoxidase catalyzes the reaction of chloride ions with H(2)O(2) to yield hypochlorous acid (HOCl), which can damage proteins. Human myoglobin (HMb) differs from other Mbs by the presence of a cysteine residue at position 110 (Cys110). This study has (i) compared wild-type and a Cys110Ala variant of HMb to assess the influence of Cys110 on HOCl-induced amino acid modification and (ii) determined whether HOCl oxidation of HMb affects the rate of ferric heme reduction by cytochrome b(5). For wild-type HMb (HOCl:Mb ratio of 5:1 mol:mol), Cys110 was preferentially oxidized to a homodimeric or cysteic acid product-sulfenic/sulfinic acids were not detected. At a HOCl:Mb ratio 10:1 mol:mol, methionine (Met) oxidation was detected, and this was enhanced in the Cys110Ala variant. Tryptophan (Trp) oxidation was detected only in the Cys110Ala variant at the highest HOCl dose tested, with oxidation susceptibility following the order Cys>Met>Trp. Tyrosine chlorination was evident only in reactions between HOCl and the Cys110Ala variant and at a longer incubation time (24 h), consistent with the formation via chlorine-transfer reactions from preformed chloramines. HOCl-mediated oxidation of wild-type HMb resulted in a dose-dependent decrease in the observed rate constant for ferric heme reduction (approx two-fold at HOCl:Mb of 10:1 mol:mol). These data indicate that Cys110 influences the oxidation of HMb by HOCl and that oxidation of Cys, Met, and Trp residues is associated with a decrease in the one-electron reduction of ferric HMb by other proteins; such heme-Fe(3+) reduction is critical to the maintenance of function as an oxygen storage protein in tissues.

KW - Amino Acids

KW - Cytochromes b5

KW - Heme

KW - Humans

KW - Hypochlorous Acid

KW - Iron

KW - Myoglobin

KW - Oxidation-Reduction

KW - Recombinant Proteins

U2 - 10.1016/j.freeradbiomed.2009.09.023

DO - 10.1016/j.freeradbiomed.2009.09.023

M3 - Journal article

C2 - 19800968

VL - 48

SP - 35

EP - 46

JO - Free Radical Biology & Medicine

JF - Free Radical Biology & Medicine

SN - 0891-5849

IS - 1

ER -

ID: 129670257