Crystal structure of peroxiredoxin 3 from Vibrio vulnificus and its implications for scavenging peroxides and nitric oxide

Peroxiredoxins (Prxs) are ubiquitous cysteine-based peroxidase enzymes. Recently, a new type of Prx, VvPrx3, was identified in the pathogenic bacterium Vibrio vulnificus as being important for survival in macrophages. It employs only one catalytic cysteine residue to decompose peroxides. Here, crystal structures of VvPrx3 representing its reduced and oxidized states have been determined, together with an H2O2-bound structure, at high resolution. The crystal structure representing the reduced Prx3 showed a typical dimeric interface, called the A-type interface. However, VvPrx3 forms an oligomeric interface mediated by a disulfide bond between two catalytic cysteine residues from two adjacent dimers, which differs from the doughnut-like oligomers that appear in most Prxs. Subsequent biochemical studies showed that this disulfide bond was induced by treatment with nitric oxide (NO) as well as with peroxides. Consistently, NO treatment induced expression of the prx3 gene in V. vulnificus, and VvPrx3 was crucial for the survival of bacteria in the presence of NO. Taken together, the function and mechanism of VvPrx3 in scavenging peroxides and NO stress via oligomerization are proposed. These findings contribute to the understanding of the diverse functions of Prxs during pathogenic processes at the molecular level.

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Modification of Glyceraldehyde-3-Phosphate Dehydrogenase with Nitric Oxide: Role in Signal Transduction and Development of Apoptosis

Biomolecules ◽

10.3390/biom11111656 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1656

Author(s):

Vladimir I. Muronetz ◽

Maria V. Medvedeva ◽

Irina A. Sevostyanova ◽

Elena V. Schmalhausen

Keyword(s):

Nitric Oxide ◽

Signal Transduction ◽

Cysteine Residue ◽

Nuclear Proteins ◽

Passive Transport ◽

Carrier Proteins ◽

Catalytic Cysteine ◽

Induction Of Apoptosis ◽

Direct Confirmation

This review focuses on the consequences of GAPDH S-nitrosylation at the catalytic cysteine residue. The widespread hypothesis according to which S-nitrosylation causes a change in GAPDH structure and its subsequent binding to the Siah1 protein is considered in detail. It is assumed that the GAPDH complex with Siah1 is transported to the nucleus by carrier proteins, interacts with nuclear proteins, and induces apoptosis. However, there are several conflicting and unproven elements in this hypothesis. In particular, there is no direct confirmation of the interaction between the tetrameric GAPDH and Siah1 caused by S-nitrosylation of GAPDH. The question remains as to whether the translocation of GAPDH into the nucleus is caused by S-nitrosylation or by some other modification of the catalytic cysteine residue. The hypothesis of the induction of apoptosis by oxidation of GAPDH is considered. This oxidation leads to a release of the coenzyme NAD+ from the active center of GAPDH, followed by the dissociation of the tetramer into subunits, which move to the nucleus due to passive transport and induce apoptosis. In conclusion, the main tasks are summarized, the solutions to which will make it possible to more definitively establish the role of nitric oxide in the induction of apoptosis.

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Organometallic ruthenium anticancer complexes inhibit human peroxiredoxin I activity by binding to and inducing oxidation of its catalytic cysteine residue

Metallomics ◽

10.1039/c8mt00352a ◽

2019 ◽

Vol 11 (3) ◽

pp. 546-555 ◽

Cited By ~ 1

Author(s):

Yu Lin ◽

Jie Wang ◽

Wei Zheng ◽

Qun Luo ◽

Kui Wu ◽

...

Keyword(s):

Disulfide Bond ◽

Cysteine Residue ◽

Catalytic Cysteine ◽

Anticancer Complexes ◽

Ruthenium Arene ◽

Peroxiredoxin I

Ruthenium arene anticancer complexes bind to human peroxiredoxin I, leading to oxidation of thiolate and failure of forming a disulfide bond.

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Crystal structure of an inclusion complex between chiral monoaza-15-crown-5 and S(–)-1-phenyl-ethyl ammonium percholorate

Zeitschrift für Kristallographie - Crystalline Materials ◽

10.1524/zkri.218.5.381.20734 ◽

2003 ◽

Vol 218 (5) ◽

Cited By ~ 5

Author(s):

Süheyla Özbey ◽

F. B. Kaynak ◽

M. Toğrul ◽

N. Demirel ◽

H. Hoşgören

Keyword(s):

Crystal Structure ◽

Inclusion Complex ◽

Single Crystal ◽

X Ray Diffraction ◽

Space Group ◽

X Ray ◽

New Type

AbstractA new type of inclusion complex, S(–)-1 phenyl ethyl ammonium percholorate complex of R-(–)-2-ethyl - N - benzyl - 4, 7, 10, 13 - tetraoxa -1- azacyclopentadecane, has been prepared and studied by NMR, IR and single crystal X-ray diffraction techniques. The compound crystallizes in space group

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Unique Cellular and Biochemical Features of Human Mitochondrial Peroxiredoxin 3 Establish the Molecular Basis for Its Specific Reaction with Thiostrepton

Antioxidants ◽

10.3390/antiox10020150 ◽

2021 ◽

Vol 10 (2) ◽

pp. 150

Author(s):

Kimberly J. Nelson ◽

Terri Messier ◽

Stephanie Milczarek ◽

Alexis Saaman ◽

Stacie Beuschel ◽

...

Keyword(s):

Oxygen Species ◽

Mitochondrial Reactive Oxygen Species ◽

Wild Type ◽

Cellular Models ◽

Chemotherapeutic Approach ◽

Promising Target ◽

Redox Responsive ◽

Catalytic Cysteine ◽

Increased Sensitivity ◽

Peroxiredoxin 3

A central hallmark of tumorigenesis is metabolic alterations that increase mitochondrial reactive oxygen species (mROS). In response, cancer cells upregulate their antioxidant capacity and redox-responsive signaling pathways. A promising chemotherapeutic approach is to increase ROS to levels incompatible with tumor cell survival. Mitochondrial peroxiredoxin 3 (PRX3) plays a significant role in detoxifying hydrogen peroxide (H2O2). PRX3 is a molecular target of thiostrepton (TS), a natural product and FDA-approved antibiotic. TS inactivates PRX3 by covalently adducting its two catalytic cysteine residues and crosslinking the homodimer. Using cellular models of malignant mesothelioma, we show here that PRX3 expression and mROS levels in cells correlate with sensitivity to TS and that TS reacts selectively with PRX3 relative to other PRX isoforms. Using recombinant PRXs 1–5, we demonstrate that TS preferentially reacts with a reduced thiolate in the PRX3 dimer at mitochondrial pH. We also show that partially oxidized PRX3 fully dissociates to dimers, while partially oxidized PRX1 and PRX2 remain largely decameric. The ability of TS to react with engineered dimers of PRX1 and PRX2 at mitochondrial pH, but inefficiently with wild-type decameric protein at cytoplasmic pH, supports a novel mechanism of action and explains the specificity of TS for PRX3. Thus, the unique structure and propensity of PRX3 to form dimers contribute to its increased sensitivity to TS-mediated inactivation, making PRX3 a promising target for prooxidant cancer therapy.

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A 2-D Zn(II) coordination polymer based on 4,5-imidazoledicarboxylate and bis(benzimidazole) ligands: synthesis, crystal structure and fluorescence properties

Zeitschrift für Naturforschung B ◽

10.1515/znb-2021-0003 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Xinzhao Xia ◽

Lixian Xia ◽

Geng Zhang ◽

Yuxuan Jiang ◽

Fugang Sun ◽

...

Keyword(s):

Crystal Structure ◽

Coordination Polymer ◽

Zigzag Chain ◽

Supramolecular Framework ◽

X Ray Diffraction ◽

Hydrothermal Conditions ◽

Hydrogen Bond Interaction ◽

X Ray ◽

New Type ◽

Solid State Fluorescence

Abstract In this work, a new type of zinc(II) coordination polymer {[Zn(HIDC)(BBM)0.5]·H2O} n (Zn-CP) was synthesized using 4,5-imidazoledicarboxylic acid (H3IDC) and 2,2-(1,4-butanediyl)bis-1,3-benzimidazole (BBM) under hydrothermal conditions. Its structure has been characterized by infrared spectroscopy, elemental analysis and single crystal X-ray diffraction analysis. The Zn(II) ion is linked by the HIDC2− ligand to form a zigzag chain by chelating and bridging, and then linked by BBM to form a layered network structure. Adjacent layers are further connected by hydrogen bond interaction to form a 3-D supramolecular framework. The solid-state fluorescence performance of Zn-CP shows that compared with free H3IDC ligand, its fluorescence intensity is significantly enhanced.

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