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

Biochem J. 2005 Jan 15;385(Pt 2):427-32. doi: 10.1042/BJ20041218.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution / genetics
  • Aorta / enzymology
  • Arginine / chemistry
  • Arginine / genetics
  • Arginine / metabolism*
  • Chromatography, Affinity / methods
  • Chromatography, Agarose / methods
  • Circular Dichroism / methods
  • Collagen / metabolism*
  • Extracellular Matrix / metabolism*
  • Glycine / chemistry
  • Glycine / genetics
  • Glycine / metabolism*
  • Heparin / metabolism*
  • Humans
  • Hydrogen-Ion Concentration
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / metabolism
  • Substrate Specificity
  • Superoxide Dismutase / blood*
  • Superoxide Dismutase / chemistry
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*


  • Peptides
  • Heparin
  • Collagen
  • Arginine
  • SOD3 protein, human
  • Superoxide Dismutase
  • Glycine