Distinct metal-binding configurations in metallothionein.

Nielson, K B; Atkin, Curtis L.; Winge, Dennis R.

doi:10.1016/s0021-9258(18)89027-5

Cited by 309 publications

(90 citation statements)

References 39 publications

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“…Metallothioneins are a group of small conserved, metal-binding proteins, rich in the amino acid cysteine, which allow them to bind several trace metals, such as copper, iron, and zinc via their -SH functionality (Reviewed in [ 44 ]). In addition to their role in protecting against oxidative stress, metallothioneins also provide an important buffering function against toxic heavy metals [ 45 ]. Together, these molecules provide an important first line of defense in limiting the formation of ROS.…”

Section: Burn Treatment With Antioxidantsmentioning

confidence: 99%

Decreasing the Likelihood of Multiple Organ Dysfunction Syndrome in Burn Injury with Early Antioxidant Treatment

Sterling

Lombardi

2021

Antioxidants

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Major burn trauma initiates a cascade of physiological events that cause profound stress on the body, resulting in significant complications which often lead to death. An understanding of these events may afford earlier and more precise interventions which, in turn, may reduce these complications, thus, improving patient outcomes. Burn trauma is associated with numerous inflammatory events that result in the release of free radicals, which promote oxidative stress and subsequent tissue damage. These mass-inflammatory events affect the body systemically, leading to several detrimental responses including complement activation, excessive histamine release, decrease in blood pressure, release of reactive oxygen species, and ultimately multiple organ dysfunction syndrome (MODS). However, recent studies conducted on the use of antioxidants as a part of a burn treatment protocol have shown promising results. In this review, we will discuss the current research and advancements in the treatment of burn trauma with the use of antioxidants, and how the early administration of antioxidant can possibly reduce the risk of developing MODS.

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Section: Burn Treatment With Antioxidantsmentioning

confidence: 99%

Decreasing the Likelihood of Multiple Organ Dysfunction Syndrome in Burn Injury with Early Antioxidant Treatment

Sterling

Lombardi

2021

Antioxidants

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“…A number of studies of the stoichiometry of binding of copper to mammalian metallothionein (MT) have produced variable results, ranging from 7 to 15 or more Cu per mol of protein [1]. In some cases titration experiments were carried out, in which Cu-containing MTs were generated in itro [2][3][4][5][6]. Generally, endpoints were defined by breaks in spectrophotometric or CD titration plots, not by measurement of metals bound to the protein.…”

Section: Introductionmentioning

confidence: 99%

Stoichiometry and cluster specificity of copper binding to metallothionein: homogeneous metal clusters

Chen

Muñoz

Nettesheim

et al. 1996

Biochemical Journal

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Experiments were done to define the stoichiometry of binding of Cu(I) to metallothionein (MT) and to determine its sites of binding in mixed-metal species. Spectrophotometric titrations of rabbit liver Cd7-MT 2, apoMT, and Cd4-alpha-domain with Cu(I) revealed endpoints of 3-4, 4 and 8, and 4 and 6-7 added Cu(I)/mol of MT for the three species respectively. Observed endpoints depended on conditions of the titration and the wavelength chosen for absorbance measurement. Nevertheless, from metal and sulphydryl analyses of titrated proteins that were pretreated with Chelex-100 to remove metal ions from solution, almost all of the cadmium was displaced from Cd7-MT by the addition of 7 Cu(I)/mol of MT. Similarly, 4 Cu(I)/mol of Cd4-alpha-domain completely displaced bound cadmium. The Cu4-alpha-domain was converted into a Cu6-alpha species upon addition of two equivalents of Cu(I)/mol of alpha-domain. Reaction of Cd7-MT with 7, 12 and 20 Cu/mol of MT, followed by reaction with Chelex resin, generated protein samples in each case with about 7 Cu/mol of MT. 111Cd-NMR analysis of the reaction of 111Cd7-MT with Cu(I) showed that nearly co-operative one-for-one replacement of 111Cd occurred and that the beta-domain cluster reacted before the alpha-domain cluster. Two mixed-metal MTs with Cu to Zn ratios approximating 3 to 4 and 6 to 4 were isolated from calf liver. After substitution of Zn with 111Cd, NMR spectra of each protein showed that 111Cd was confined almost completely to the alpha-domain. By inference, about 3 or 6 Cu were bound in the beta-domain of these proteins. Supporting this segregation of metal ions into domains, reaction of Cu6, Zn4-MT with nitrilotriacetate removed zinc exclusively, whereas reaction of Cu6,Cd4-MT with 4,7-phenylsulphonyl-2,9-dimethyl-1,10-phenanthroline extracted only Cu(I). Proteolytic digestion of both products followed by gel filtration demonstrated that Cu(I) and Cd were bound to fragments of the intact protein. Finally, reaction of rabbit liver 111Cd7-MT 2 with Cu10-MT 2 resulted in interprotein metal exchange in which 111Cd-moved from the beta- to the alpha-domain according to NMR analysis. In contrast with the prevalent view that six Cu(I) bind to each domain of MT, the present results show that Cu(I) binds to MT with a minimum stoichiometry of about 7 Cu(I)/mol of MT and can bind to the alpha-domain with stoichiometries of 4 or 6 Cu(I)/mol of MT. Although MTs interacting with 12 or 20 Cu(I)/mol of MT are less stable than that binding about 7 Cu(I)/mol, it appears that MT can bind Cu(I) in multiple stoichiometries.

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“…Pb also binds to metallothionein, but does not appear to be a significant inducer of the protein in comparison with the inducers of cadmium and zinc (Eaton et al 1980;Waalkes and Klaassen 1985). In vivo, only a small fraction of the Pb in the kidney is bound to metallothionein, and appears to have a binding affinity that is less than Cd 2+ , but higher than Zn 2+ (Ulmer and Vallee 1969); thus, Pb will more readily displace zinc from metallothionein than cadmium (Goering and Fowler 1987;Nielson et al 1985;Waalkes et al 1984).…”

Section: Toxicokinetics Susceptible Populations Biomarkers Chemical Interactionsmentioning

confidence: 99%

Toxicological profile for lead

Abadin

Ashizawa²,

Stevens³

et al. 2020

140

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This toxicological profile is prepared in accordance with guidelines developed by the Agency for Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised and republished as necessary. The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects information for these toxic substances described therein. Each peer-reviewed profile identifies and reviews the key literature that describes a substance's toxicologic properties. Other pertinent literature is also presented, but is described in less detail than the key studies. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. CAS# 7439-92-1

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Distinct metal-binding configurations in metallothionein.

Cited by 309 publications

References 39 publications

Decreasing the Likelihood of Multiple Organ Dysfunction Syndrome in Burn Injury with Early Antioxidant Treatment

Decreasing the Likelihood of Multiple Organ Dysfunction Syndrome in Burn Injury with Early Antioxidant Treatment

Stoichiometry and cluster specificity of copper binding to metallothionein: homogeneous metal clusters

Toxicological profile for lead

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