Crystal Structure of a Dimeric Oxidized form of Human Peroxiredoxin 5

Evrard, C.; Capron, Arnaud; Marchand, Cécile; Clippe, André; Wattiez, Ruddy; Soumillion, Patrice; Knoops, Bernard; Declercq, Jean‐Paul

doi:10.1016/j.jmb.2004.02.017

Cited by 75 publications

(61 citation statements)

References 42 publications

(77 reference statements)

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“…11 Interestingly, it was previously noticed 12 that the α5 helix was involved in the formation of a non-covalent dimer between two PRDX5 molecules. This kind of dimer buries about 790 Å 2 per molecule and since it is present in structures of reduced and oxidized forms of PRDX5 belonging to different space groups and systems (tetragonal for 1hd2, 10 monoclinic for 1h4o, 11 orthorhombic for loc3 12 ) it is certainly not an artefact of crystallization. This dimer is also observed in the structure of the C47S mutant and is formed by the association of two molecules related by a crystallographic twofold axis.…”

Section: Resultsmentioning

confidence: 99%

“…10,11 Another crystal form simultaneously containing the reduced state and an unexpected dimeric oxidized state was also described. 12 All the reduced molecules show that the sulfur atoms of Cys47 and Cys151 are positioned too far apart (13.8 Å) to interact in the expected intramolecular way without large conformational changes. The dimer present in all other known PRDXs structures and resulting from the association of β sheets is not observed in PRDX5.…”

Section: Introductionmentioning

confidence: 97%

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Crystal structure of the C47S mutant of human peroxiredoxin 5

Evrard

Smeets

Knoops

et al. 2004

Journal of Chemical Crystallography

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In the crystal structure of the reduced form of the wild-type human peroxiredoxin 5, the presence of a benzoate ion in direct interaction with the peroxidatic cysteine (Cys 47) appeared as a rather intriguing feature since it is known that the benzoate ion can play the role of a specific hydroxyl radical scavenger. The crystal structure of the C47S mutant of the same enzyme has been crystallized in the tetragonal system, space group P4 1 2 1 2, with a = 65.65 Å, c = 122.04 Å. It confirms the presence of this benzoate ion in spite of the mutation into a serine of the Cys 47 residue to which the benzoate ion was directly linked in the wild-type structure. The benzoate ion seems to be stabilized by hydrophobic contacts on both sides of the aromatic ring. In this matter, the α5 helix, which is specific to peroxiredoxin 5 among mammalian peroxiredoxins, plays an important role. These hydrophobic contacts also allow to suggest why the benzoate ion disappears when the molecule is oxidized.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Crystal structure of the C47S mutant of human peroxiredoxin 5

Evrard

Smeets

Knoops

et al. 2004

Journal of Chemical Crystallography

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“…Prx4 is present in the cytoplasm and is also translocated to the extracellular space because of secretory signal sequences included in the N-terminal region (115). Prx5, localized in cytosol, mitochondria, and peroxisome, has been characterized to form two intermolecular disulfide bonds, which then rearrange to form intramolecular disulfides during peroxide-induced oxidation (34). The one N-terminal Cys of Prx6 is readily oxidized by peroxide, resulting in Cys-sulfenic acid (ÀSOH) (21).…”

Section: Go and Jonesmentioning

confidence: 99%

Redox Control Systems in the Nucleus: Mechanisms and Functions

Jones

2010

Antioxidants & Redox Signaling

176

125

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Proteins with oxidizable thiols are essential to many functions of cell nuclei, including transcription, chromatin stability, nuclear protein import and export, and DNA replication and repair. Control of the nuclear thioldisulfide redox states involves both the elimination of oxidants to prevent oxidation and the reduction of oxidized thiols to restore function. These processes depend on the common thiol reductants, glutathione (GSH) and thioredoxin-1 (Trx1). Recent evidence shows that these systems are controlled independent of the cytoplasmic counterparts. In addition, the GSH and Trx1 couples are not in redox equilibrium, indicating that these reductants have nonredundant functions in their support of proteins involved in transcriptional regulation, nuclear protein trafficking, and DNA repair. Specific isoforms of glutathione peroxidases, glutathione Stransferases, and peroxiredoxins are enriched in nuclei, further supporting the interpretation that functions of the thiol-dependent systems in nuclei are at least quantitatively distinct, and probably also qualitatively distinct, from similar processes in the cytoplasm. Elucidation of the distinct nuclear functions and regulation of the thiol redox pathways in nuclei can be expected to improve understanding of nuclear processes and also to provide the basis for novel approaches to treat aging and disease processes associated with oxidative stress in the nuclei. Antioxid. Redox Signal. 13, 489-509.

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“…Human type II PRX, HsPRXV, contains three cysteine residues. Once oxidized to SOH the peroxidatic cys47 forms a disulfide with cys151 that can be reduced by TRX (Evrard et al 2004). Chlamydomonas type II CrPRX4 is related to Arabidopsis mitochondrial PRXIIF, which can reduce a broad range of substrates but more efficiently H 2 O 2 than alkylhydroperoxides (Horling et al 2003).…”

Section: The Peroxiredoxin Familymentioning

confidence: 99%

The Peroxiredoxin and Glutathione Peroxidase Families in Chlamydomonas reinhardtii

et al. 2008

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Thiol/selenol peroxidases are ubiquitous nonheme peroxidases. They are divided into two major subfamilies: peroxiredoxins (PRXs) and glutathione peroxidases (GPXs). PRXs are present in diverse subcellular compartments and divided into four types: 2-cys PRX, 1-cys PRX, PRX-Q , and type II PRX (PRXII). In mammals, most GPXs are selenoenzymes containing a highly reactive selenocysteine in their active site while yeast and land plants are devoid of selenoproteins but contain nonselenium GPXs. The presence of a chloroplastic 2-cys PRX, a nonselenium GPX, and two selenium-dependent GPXs has been reported in the unicellular green alga Chlamydomonas reinhardtii. The availability of the Chlamydomonas genome sequence offers the opportunity to complete our knowledge on thiol/selenol peroxidases in this organism. In this article, Chlamydomonas PRX and GPX families are presented and compared to their counterparts in Arabidopsis, human, yeast, and Synechocystis sp. A summary of the current knowledge on each family of peroxidases, especially in photosynthetic organisms, phylogenetic analyses, and investigations of the putative subcellular localization of each protein and its relative expression level, on the basis of EST data, are presented. We show that Chlamydomonas PRX and GPX families share some similarities with other photosynthetic organisms but also with human cells. The data are discussed in view of recent results suggesting that these enzymes are important scavengers of reactive oxygen species (ROS) and reactive nitrogen species (RNS) but also play a role in ROS signaling. L IFE in an oxygen-rich environment has to deal with the danger of oxidative stress. During normal cell metabolism, reactive oxygen species (ROS) and reactive nitrogen species (RNS) are constantly produced, essentially by respiratory and photosynthetic electron transfer chains. These highly reactive molecules can react with many cell components and damage DNA, proteins, and lipids. Thus, their concentration has to be strictly controlled. For this purpose, aerobic organisms are equipped with nonenzymatic (ascorbate, glutathione, tocopherol, and carotenoid) or enzymatic (catalase, ascorbate peroxidase, superoxide dismutase, glutathione peroxidase, and peroxiredoxin) antioxidant systems to remove ROS from the cells. To control their concentrations, ROS and RNS have to be sensed. It has been established in many organisms that ROS, and especially hydrogen peroxide, are signaling molecules that diffuse across membranes and induce specific signal transduction pathways. Furthermore, ROS can also be produced on purpose by cells in response to several stimuli to function as second messengers inside the cell. Finally, ROS and RNS can control enzyme activities by triggering several post-translational modifications such as disulfide bond formation, thiol oxidation to sulfenic/sulfinic/sulfonic acid, glutathionylation, nitrosylation, or carbonylation.Thiol/selenol peroxidases have emerged, during recent years, as important scavengers of ROS/RNS but they ...

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Crystal Structure of a Dimeric Oxidized form of Human Peroxiredoxin 5

Cited by 75 publications

References 42 publications

Crystal structure of the C47S mutant of human peroxiredoxin 5

Crystal structure of the C47S mutant of human peroxiredoxin 5

Redox Control Systems in the Nucleus: Mechanisms and Functions

The Peroxiredoxin and Glutathione Peroxidase Families in Chlamydomonas reinhardtii

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