The high concentration of Arg213 → Gly extracellular superoxide dismutase (EC-SOD) in plasma is caused by a reduction of both heparin and collagen affinities

Steen V. Petersen; Dorte Aa Olsen; John M. Kenney; Tim D. Oury; Zuzana Valnickova; Ida B. Thøgersen; James D. Crapos; Jan J. Enghild

doi:10.1042/BJ20041218

The high concentration of Arg213 → Gly extracellular superoxide dismutase (EC-SOD) in plasma is caused by a reduction of both heparin and collagen affinities

Steen V. Petersen, Dorte Aa Olsen, John M. Kenney, Tim D. Oury, Zuzana Valnickova, Ida B. Thøgersen, James D. Crapos, Jan J. Enghild^*

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

40 Citations (Scopus)

Abstract

The C-terminal region of EC-SOD (extracellular superoxide dismutase) mediates the binding to both heparin/heparan sulphate and type I collagen. A mutation (Arg²¹³ → Gly; R213G) within this extracellular matrix-binding region has recently been implicated in the development of heart disease. This relatively common mutation affects the heparin affinity, and the concentration of EC-SOD in the plasma of R213G homozygous individuals is increased 10- to 30-fold. In the present study we confirm, using R213G EC-SOD purified from a homozygous individual, that the heparin affinity is reduced. Significantly, the collagen affinity of the R213G EC-SOD variant was similarly affected and both the heparin and collagen affinities were reduced by 12-fold. Structural analysis of synthetic extracellular matrix-binding regions suggests that the mutation alters the secondary structure. We conclude that the increased concentration of EC-SOD in the plasma of R213G carriers is caused by a reduction in both heparin and collagen affinities.

Original language	English
Journal	Biochemical Journal
Volume	385
Issue	2
Pages (from-to)	427-432
Number of pages	6
ISSN	0264-6021
DOIs	https://doi.org/10.1042/BJ20041218
Publication status	Published - 15 Jan 2005

Keywords

Arg → Gly (R213G)
Collagen
Extracellular superoxide dismutase (EC-SOD)
Oxidative damage
Reduced affinity
Structure

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10.1042/BJ20041218

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title = "The high concentration of Arg213 → Gly extracellular superoxide dismutase (EC-SOD) in plasma is caused by a reduction of both heparin and collagen affinities",

abstract = "The C-terminal region of EC-SOD (extracellular superoxide dismutase) mediates the binding to both heparin/heparan sulphate and type I collagen. A mutation (Arg213 → Gly; R213G) within this extracellular matrix-binding region has recently been implicated in the development of heart disease. This relatively common mutation affects the heparin affinity, and the concentration of EC-SOD in the plasma of R213G homozygous individuals is increased 10- to 30-fold. In the present study we confirm, using R213G EC-SOD purified from a homozygous individual, that the heparin affinity is reduced. Significantly, the collagen affinity of the R213G EC-SOD variant was similarly affected and both the heparin and collagen affinities were reduced by 12-fold. Structural analysis of synthetic extracellular matrix-binding regions suggests that the mutation alters the secondary structure. We conclude that the increased concentration of EC-SOD in the plasma of R213G carriers is caused by a reduction in both heparin and collagen affinities.",

keywords = "Arg → Gly (R213G), Collagen, Extracellular superoxide dismutase (EC-SOD), Oxidative damage, Reduced affinity, Structure",

author = "Petersen, {Steen V.} and Olsen, {Dorte Aa} and Kenney, {John M.} and Oury, {Tim D.} and Zuzana Valnickova and Th{\o}gersen, {Ida B.} and Crapos, {James D.} and Enghild, {Jan J.}",

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The high concentration of Arg213 → Gly extracellular superoxide dismutase (EC-SOD) in plasma is caused by a reduction of both heparin and collagen affinities. / Petersen, Steen V.; Olsen, Dorte Aa; Kenney, John M. et al.
In: Biochemical Journal, Vol. 385, No. 2, 15.01.2005, p. 427-432.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - The high concentration of Arg213 → Gly extracellular superoxide dismutase (EC-SOD) in plasma is caused by a reduction of both heparin and collagen affinities

AU - Petersen, Steen V.

AU - Olsen, Dorte Aa

AU - Kenney, John M.

AU - Oury, Tim D.

AU - Valnickova, Zuzana

AU - Thøgersen, Ida B.

AU - Crapos, James D.

AU - Enghild, Jan J.

PY - 2005/1/15

Y1 - 2005/1/15

N2 - The C-terminal region of EC-SOD (extracellular superoxide dismutase) mediates the binding to both heparin/heparan sulphate and type I collagen. A mutation (Arg213 → Gly; R213G) within this extracellular matrix-binding region has recently been implicated in the development of heart disease. This relatively common mutation affects the heparin affinity, and the concentration of EC-SOD in the plasma of R213G homozygous individuals is increased 10- to 30-fold. In the present study we confirm, using R213G EC-SOD purified from a homozygous individual, that the heparin affinity is reduced. Significantly, the collagen affinity of the R213G EC-SOD variant was similarly affected and both the heparin and collagen affinities were reduced by 12-fold. Structural analysis of synthetic extracellular matrix-binding regions suggests that the mutation alters the secondary structure. We conclude that the increased concentration of EC-SOD in the plasma of R213G carriers is caused by a reduction in both heparin and collagen affinities.

AB - The C-terminal region of EC-SOD (extracellular superoxide dismutase) mediates the binding to both heparin/heparan sulphate and type I collagen. A mutation (Arg213 → Gly; R213G) within this extracellular matrix-binding region has recently been implicated in the development of heart disease. This relatively common mutation affects the heparin affinity, and the concentration of EC-SOD in the plasma of R213G homozygous individuals is increased 10- to 30-fold. In the present study we confirm, using R213G EC-SOD purified from a homozygous individual, that the heparin affinity is reduced. Significantly, the collagen affinity of the R213G EC-SOD variant was similarly affected and both the heparin and collagen affinities were reduced by 12-fold. Structural analysis of synthetic extracellular matrix-binding regions suggests that the mutation alters the secondary structure. We conclude that the increased concentration of EC-SOD in the plasma of R213G carriers is caused by a reduction in both heparin and collagen affinities.

KW - Arg → Gly (R213G)

KW - Collagen

KW - Extracellular superoxide dismutase (EC-SOD)

KW - Oxidative damage

KW - Reduced affinity

KW - Structure

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DO - 10.1042/BJ20041218

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SN - 0264-6021

VL - 385

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EP - 432

JO - Biochemical Journal

JF - Biochemical Journal

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The high concentration of Arg213 → Gly extracellular superoxide dismutase (EC-SOD) in plasma is caused by a reduction of both heparin and collagen affinities

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