Characterization of a covalent polysulfane bridge in copper-zinc superoxide dismutase

Zheng You, Xiaohang Cao, Alexander B. Taylor, P. John Hart, Rodney L. Levine

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

In the course of studies on human copper-zinc superoxide dismutase (SOD1), we observed a modified form of the protein whose mass was increased by 158 mass units. The covalent modification was characterized, and we established that it is a novel heptasulfane bridge connecting the two Cys111 residues in the SOD1 homodimer. The heptasulfane bridge was visualized directly in the crystal structure of a recombinant human mutant SOD1, H46R/H48Q, produced in yeast. The modification is reversible, with the bridge being cleaved by thiols, by cyanide, and by unfolding of the protein to expose the polysulfane. The polysulfane bridge can be introduced in vitro by incubation of purified SOD1 with elemental sulfur, even under anaerobic conditions and in the presence of a metal chelator. Because polysulfanes and polysulfides can catalyze the generation of reactive oxygen and sulfur species, the modification may endow SOD1 with a toxic gain of function.

Original languageEnglish (US)
Pages (from-to)1191-1198
Number of pages8
JournalBiochemistry
Volume49
Issue number6
DOIs
StatePublished - Feb 16 2010

Fingerprint

Sulfur
Superoxide Dismutase
Zinc
Copper
Protein Unfolding
Poisons
Cyanides
Chelating Agents
Sulfhydryl Compounds
Reactive Oxygen Species
Yeasts
Metals
Yeast
Proteins
Crystal structure
Oxygen
In Vitro Techniques
polysulfide

ASJC Scopus subject areas

  • Biochemistry

Cite this

Characterization of a covalent polysulfane bridge in copper-zinc superoxide dismutase. / You, Zheng; Cao, Xiaohang; Taylor, Alexander B.; Hart, P. John; Levine, Rodney L.

In: Biochemistry, Vol. 49, No. 6, 16.02.2010, p. 1191-1198.

Research output: Contribution to journalArticle

You, Zheng ; Cao, Xiaohang ; Taylor, Alexander B. ; Hart, P. John ; Levine, Rodney L. / Characterization of a covalent polysulfane bridge in copper-zinc superoxide dismutase. In: Biochemistry. 2010 ; Vol. 49, No. 6. pp. 1191-1198.
@article{894cf1dc29194ea29a53e974063b8db4,
title = "Characterization of a covalent polysulfane bridge in copper-zinc superoxide dismutase",
abstract = "In the course of studies on human copper-zinc superoxide dismutase (SOD1), we observed a modified form of the protein whose mass was increased by 158 mass units. The covalent modification was characterized, and we established that it is a novel heptasulfane bridge connecting the two Cys111 residues in the SOD1 homodimer. The heptasulfane bridge was visualized directly in the crystal structure of a recombinant human mutant SOD1, H46R/H48Q, produced in yeast. The modification is reversible, with the bridge being cleaved by thiols, by cyanide, and by unfolding of the protein to expose the polysulfane. The polysulfane bridge can be introduced in vitro by incubation of purified SOD1 with elemental sulfur, even under anaerobic conditions and in the presence of a metal chelator. Because polysulfanes and polysulfides can catalyze the generation of reactive oxygen and sulfur species, the modification may endow SOD1 with a toxic gain of function.",
author = "Zheng You and Xiaohang Cao and Taylor, {Alexander B.} and Hart, {P. John} and Levine, {Rodney L.}",
year = "2010",
month = "2",
day = "16",
doi = "10.1021/bi901844d",
language = "English (US)",
volume = "49",
pages = "1191--1198",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "6",

}

TY - JOUR

T1 - Characterization of a covalent polysulfane bridge in copper-zinc superoxide dismutase

AU - You, Zheng

AU - Cao, Xiaohang

AU - Taylor, Alexander B.

AU - Hart, P. John

AU - Levine, Rodney L.

PY - 2010/2/16

Y1 - 2010/2/16

N2 - In the course of studies on human copper-zinc superoxide dismutase (SOD1), we observed a modified form of the protein whose mass was increased by 158 mass units. The covalent modification was characterized, and we established that it is a novel heptasulfane bridge connecting the two Cys111 residues in the SOD1 homodimer. The heptasulfane bridge was visualized directly in the crystal structure of a recombinant human mutant SOD1, H46R/H48Q, produced in yeast. The modification is reversible, with the bridge being cleaved by thiols, by cyanide, and by unfolding of the protein to expose the polysulfane. The polysulfane bridge can be introduced in vitro by incubation of purified SOD1 with elemental sulfur, even under anaerobic conditions and in the presence of a metal chelator. Because polysulfanes and polysulfides can catalyze the generation of reactive oxygen and sulfur species, the modification may endow SOD1 with a toxic gain of function.

AB - In the course of studies on human copper-zinc superoxide dismutase (SOD1), we observed a modified form of the protein whose mass was increased by 158 mass units. The covalent modification was characterized, and we established that it is a novel heptasulfane bridge connecting the two Cys111 residues in the SOD1 homodimer. The heptasulfane bridge was visualized directly in the crystal structure of a recombinant human mutant SOD1, H46R/H48Q, produced in yeast. The modification is reversible, with the bridge being cleaved by thiols, by cyanide, and by unfolding of the protein to expose the polysulfane. The polysulfane bridge can be introduced in vitro by incubation of purified SOD1 with elemental sulfur, even under anaerobic conditions and in the presence of a metal chelator. Because polysulfanes and polysulfides can catalyze the generation of reactive oxygen and sulfur species, the modification may endow SOD1 with a toxic gain of function.

UR - http://www.scopus.com/inward/record.url?scp=76749156792&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=76749156792&partnerID=8YFLogxK

U2 - 10.1021/bi901844d

DO - 10.1021/bi901844d

M3 - Article

VL - 49

SP - 1191

EP - 1198

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 6

ER -