Sulfur ligation in copper enzymes and models

Belle, Catherine; Rammal, Wassim; Pierre, Jean‐Louis

doi:10.1016/j.jinorgbio.2005.06.013

Cited by 73 publications

(54 citation statements)

References 56 publications

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“…The obtained data do not exclude a direct involvement of disulfide sulfur(s) in Cu(I) coordination. In inorganic model complexes a direct Cu(I) coordination by a disulfide bridge sulfur has been reported (66,67). The presence of two disulfides in the ␤-domain, leaving five reduced free thiolate ligands, would be sufficient to coordinate 4 Cu(I) ions through terminal and bridging sulfurs in digonal or trigonal coordination.…”

Section: Discussionmentioning

confidence: 99%

Redox Silencing of Copper in Metal-linked Neurodegenerative Disorders

Meloni

Faller

Vašák

2007

Journal of Biological Chemistry

120

159

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Dysregulation of copper and zinc homeostasis in the brain plays a critical role in Alzheimer disease (AD). Copper binding to amyloid-␤ peptide (A␤) is linked with the neurotoxicity of A␤and free radical damage. Metallothionein-3 (MT-3) is a small cysteine-and metal-rich protein expressed in the brain and found down-regulated in AD. This protein occurs intra-and extracellularly, and it plays an important role in the metabolism of zinc and copper. In cell cultures Zn 7 MT-3, by an unknown mechanism, protects neurons from the toxicity of A␤. We have, therefore, used a range of complementary spectroscopic and biochemical methods to characterize the interaction of Zn 7 MT-3 with free Cu 2؉ ions. We show that Zn 7 MT-3 scavenges free Cu Essential transition metals like copper and zinc play a critical role in neurobiology. The homeostasis of both metals is tightly regulated and essential for brain physiology (1). In vitro evidence suggests that in physiological conditions micromolar concentrations of zinc and copper are actively released from neurons during neurotransmission processes into pre-and postsynaptic clefts. However, at present it is not known whether the released copper is present in a chemically exchangeable form (2). Dysregulated metal metabolism (zinc and copper) occurs in neurodegenerative disorders such as Alzheimer (3, 4), Parkinson (5), and prion (6) diseases. In these diseases increased extracellular copper concentrations and free-radical production have been found. There is now direct evidence that copper is bound to amyloid-␤ peptide (A␤) 2 in senile plaque of Alzheimer disease (AD) (7). Copper is also linked with the neurotoxicity of A␤ and free radical damage (8).Because of its redox-active nature (Cu ϩ /Cu 2ϩ ), its reactivity with molecular oxygen (O 2 ) generates the reactive oxygen species (ROS) such as superoxide, hydrogen peroxide, and hydroxyl radicals (9, 10). The redox cycling of copper requires its reduction by biological components, including ascorbate, which actively accumulates in the brain at concentrations between 0.5 and 10 mM (11). Hence, copper chelation and its redox-silencing may represent critical events in preventing the progression of neurodegenerative diseases. In recent years a metal chelation therapy has emerged as a promising tool to attenuate abnormal metal-protein interactions that lead to increased free-radical toxicity (10).The natural metal chelator metallothionein-3 (MT-3), also known as the growth inhibitory factor, is a small non-inducible cysteine-and metal-rich protein mainly expressed in the brain. In the brain its expression was found in zinc-enriched neurons. Like other mammalian metallothioneins (MTs), MT-3 binds with a high affinity essential monovalent and divalent d 10 metal ions Cu(I) and Zn(II). Recently, the interaction of Zn 7 MT-3 with the small-GTPase Rab3a, which is strictly linked to the exo-endocytotic cycle of synaptic vesicles, has been demonstrated. It has been suggested that Zn 7 MT-3 actively participates in synaptic cycle of zinc vesicles...

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Section: Discussionmentioning

confidence: 99%

Redox Silencing of Copper in Metal-linked Neurodegenerative Disorders

Meloni

Faller

Vašák

2007

Journal of Biological Chemistry

120

159

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“…4a). This suggests that coordination by a disulfide bridge sulfur has been seen 41,42 . Nevertheless, the stability of the Cu(I) 4 -thiolate cluster in air oxygen is striking and not understood.…”

Section: Zn 7 Mt-3 Protects Cells Against Aβ 1-40 Toxicitymentioning

confidence: 97%

Metal swap between Zn7-metallothionein-3 and amyloid-β–Cu protects against amyloid-β toxicity

et al. 2008

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Metal swap between Zn7metallothionein-3 and amyloid-β-Cu protects against amyloid-β toxicity Meloni, G; Sonois, V; Delaine, T; Guilloreau , L; Gillet, A; Teissie, J; Faller, P; Vasak, M Meloni, G; Sonois, V; Delaine, T; Guilloreau , L; Gillet, A; Teissie, J; Faller, P; Vasak, M (2008). Metal swap between Zn7metallothionein-3 and amyloid-β-Cu protects against amyloid-β toxicity. Nature Chemical Biology, 4 Metal swap between Zn7metallothionein-3 and amyloid-β-Cu protects against amyloid-β toxicity Abstract Aberrant interactions of copper and zinc ions with the amyloid-β peptide (Aβ) potentiate Alzheimer disease (AD) by participating in the aggregation process of Aβ and in thegeneration of reactive oxygen species (ROS). The ROS production and the neurotoxicity of Aβ are associated with copper binding. Metallothionein-3 (Zn7MT-3), an intra-andextracellularly occurring metalloprotein, is highly expressed in the brain and down-regulated in AD. This protein protects, by an unknown mechanism, cultured neurons from the toxicity of Aβ. Herein, we show that a metal swap between Zn7MT-3 and soluble and aggregated Aβ1-40-Cu(II) abolishes the ROS production and the related cellular toxicity. In this process, copper is reduced by the protein thiolates forming Cu(I)4Zn4MT-3 in which an air stable Cu(I)4-thiolate cluster and two disulfide bonds are present. The discovered protective effect of Zn7MT-3 from the copper-mediated Aβ1-40 toxicity may lead to newtherapeutic strategies in treating AD.Metal swap between Zn 7 metallothionein-3 and amyloid-β-Cu protects against amyloid-β toxicity residue Aβ peptide, a proteolytic fragment generated from the amyloid precursor protein (APP)by β-and γ-secretases 1 . There is significant evidence indicating that the Aβ peptides can interact with metal ions such as Zn(II) and Cu(II), thereby participating in their aggregation and in the production of ROS 1, 2 . Whereas the copper-induced Aβ aggregation is related to the ROS production and neurotoxicity 3 , the zinc-induced Aβ aggregation is considered to be neuroprotective 4 . The ROS are generated by Aβ-Cu(II) through the redox cycling of copper which requires its reduction by biological components such as ascorbate (1), glutathione (2), dopamine (3), and cholesterol (4) 5,6 . A dysregulation of metal ion homeostasis, as occurs in AD, may foster an environment that promotes such degenerative conditions. The modulation of brain metal ion homeostasis, the reduction of aberrant metal-protein interactions by MPAC (metal-

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“…Yield: 24.62 g (135.8 mmol, 68%) of a colorless liquid (bp 98°C at 0.07 mbar). 1 (2), Cu-S1 2.2305 (7), Cu-S2 2.2709 (7), Cu-S3 2.2825 (7); N1-Cu-S1 105.15 (7), N1-Cu-S2 92.09 (6), N1-Cu-S3 91.63 (7), S1-Cu-S2 124.02 (3), S1-Cu-S3 113.21 (3) (4), Cu1-S1 2.2742(11), Cu1-S2 2.2907 (12), Cu1-S3 2.2733 (12); N1-Cu1-S1 108.64(10), N1-Cu1-S2 108.34(10), N1-Cu1-S3 107.63 (11), S1-Cu1-S2 108.61(4), S1-Cu1-S3 116.62(4), S2-Cu1-S3 106.74(4). 3.66 (s, 2H, SCH 2 Ph), 2.70 (t, 2H, SCH 2 ), 2.45 (t, 2H, NCH 2 ), 1.64 (quint, 2H, CH 2 CH 2 CH 2 ), 1.13 (NH 2 ).…”

Section: Synthesis Of 3-benzylmercaptopropylamine (1b)mentioning

confidence: 99%

“…In the coordination sphere of redox active metal ions such as copper or iron, sulfur-ligands effect a high redox potential, because the reduced metal center is a softer cation and therefore more efficiently coordinated by the soft sulfur donors [1,2]. One of the most prominent examples for this kind of complexes is the intensely blue colored Cu II -site of cupredoxins, which play an essential role in photosynthesis and respiration [2].…”

Section: Introductionmentioning

confidence: 99%