A study of the Pb(II) binding to recombinant mouse Zn7-metallothionein 1 and its domains by ESI TOF MS

Palacios, Òscar; Leiva‐Presa, Àngels; Atrian, Sı́lvia; Łobiński, Ryszard

doi:10.1016/j.talanta.2006.11.009

Cited by 14 publications

(9 citation statements)

References 20 publications

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“…Co-expression of MT and Cu,Zn-SOD has been reported previously in yeast [58]. Contrary to our findings, Pb administration in rats was shown to result in MT production [59] following the mechanism of Pb-substituting Zn ions in MT and free Zn ions promoting the synthesis of new MT [60].…”

Section: Discussioncontrasting

confidence: 97%

Cigarette Smoking during Pregnancy: Effects on Antioxidant Enzymes, Metallothionein and Trace Elements in Mother-Newborn Pairs

et al. 2020

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The effect of maternal smoking as a source of exposure to toxic metals Cd and Pb on superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, metallothionein (MT), Cd, Pb, Cu, Fe, Mn, Se and Zn concentrations were assessed in maternal and umbilical cord blood and placenta in 74 healthy mother-newborn pairs after term delivery. Sparse discriminant analysis (SDA) was used to identify elements with the strongest impact on the SOD, GPx and MT in the measured compartments, which was then quantified by multiple regression analysis. SOD activity was lower in maternal and cord plasma, and higher in the placenta of smokers compared to non-smokers, whereas GPx activity and MT concentration did not differ between the groups. Although active smoking during pregnancy contributed to higher maternal Cd and Pb concentrations, its contribution to the variability of SOD, GPx or MT after control for other elements identified by SDA was not significant. However, an impaired balance in the antioxidant defence observed in the conditions of relatively low-to-moderate exposure levels to Cd and Pb could contribute to an increased susceptibility of offspring to oxidative stress and risk of disease development later in life. Further study on a larger number of subjects will help to better understand complex interactions between exposure to toxic elements and oxidative stress related to maternal cigarette smoking.

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Section: Discussioncontrasting

confidence: 97%

Cigarette Smoking during Pregnancy: Effects on Antioxidant Enzymes, Metallothionein and Trace Elements in Mother-Newborn Pairs

et al. 2020

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“…16 Palacios et al demonstrated with electrospray ionization mass spectrometry that the metal content in Pb–MT2 complexes is dependent on the solution pH (neutral or 4.5). 17 Using extended X-ray absorption fine structure (EXAFS), Vasak et al measured the Pb–S distance in Pb–MT complex to be ∼2.65 Å. 18 However, crucial questions such as the difference of Pb 2+ coordination and the chemical stability and physiological function of the two Pb–MT2 complexes remain to be addressed.…”

Section: Introductionmentioning

confidence: 99%

“…Previous results from ultraviolet–visible (UV–vis) spectra and microcalorimetry have suggested that different Pb–MT complexes are formed at pH 7.0 and 4.3, respectively . Palacios et al demonstrated with electrospray ionization mass spectrometry that the metal content in Pb–MT2 complexes is dependent on the solution pH (neutral or 4.5) . Using extended X-ray absorption fine structure (EXAFS), Vasak et al measured the Pb–S distance in Pb–MT complex to be ∼2.65 Å .…”

Section: Introductionmentioning

confidence: 99%

pH-Dependent Coordination of Pb²⁺ to Metallothionein2: Structures and Insight into Lead Detoxification

Liu

Darabedian

et al. 2014

Inorg. Chem.

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Lead is a toxic heavy metal whose detoxification in organisms is mainly carried out by its coordination with some metalloproteins such as metallothioneins (MTs). Two Pb–MT complexes, named as Pb7–MT2(I) and Pb7–MT2(II), form under neutral and weakly acidic conditions, respectively. However, the structures of the two complexes, which are crucial for a better understanding of the detoxification mechanism of Pb–MTs, have not been clearly elucidated. In this Work, coordination of Pb2+ with rabbit liver apo–MT2, as well as with the two individual domains (apo−αMT2 and apo−βMT2) at different pH, were studied by combined spectroscopic (UV–visible, circular dichroism, and NMR) and computational methods. The results showed that in Pb7–MT2(I) the Pb2+ coordination is in the trigonal pyramidal Pb–S3 mode, whereas the Pb7–MT2(II) complex contains mixed trigonal pyramidal Pb–S3, distorted trigonal pyramidal Pb–S2O1, and distorted quadrilateral pyramidal Pb–S3O1 modes. The O-donor ligand in Pb7–MT2(II) was identified as the carboxyl groups of the aspartic acid residues at positions 2 and 56. Our studies also revealed that Pb7–MT2(II) has a greater acid tolerance and coordination stability than Pb7–MT2(I), thereby retaining the Pb2+ coordination at acidic pH. The higher flexibility of Pb7–MT2(II) renders it more accessible to lysosomal proteolysis than Pb7–MT2(I). Similar spectral features were observed in the coordination of Pb2+ by human apo-MT2, suggesting a commonality among mammalian MT2s in the Pb2+ coordination chemistry.

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“…These may contribute to a more stable Pb 7 MT-3 structure, perhaps consistent with a report that MT-3 has an 8th binding site for metal ions, 45 or other reports that MT can bind ''excess'' metal ions forming super-metallated complexes. 24,78 In contrast, both the Pb 2+ and Zn 2+ EDTA chelation experiments start from the canonical form with seven metal ions and thus avoid complications from the presence of excess metal ions. The seventh root of the b 7 value gives the average K value for the seven metal ions binding to MT-3.…”

Section: Discussionmentioning

confidence: 99%

“…Later studies have suggested that lead binds to metallothioneins more tightly than zinc, 75,76 although with potentially complex kinetics. 77,78 The technique of isothermal titration calorimetry (ITC) is capable of measuring the thermodynamics of metal ions binding to peptides and proteins. [79][80][81][82] To date, ITC has not been widely used to study metal ions binding to MT, which is likely due to the oxygen sensitivity of the apo protein that hampers its characterization by ITC and other methods.…”

Section: A Introductionmentioning

confidence: 99%

Thermodynamics of Pb(ii) and Zn(ii) binding to MT-3, a neurologically important metallothionein

et al. 2016

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Isothermal titration calorimetry (ITC) was used to quantify the thermodynamics of Pb(2+) and Zn(2+) binding to metallothionein-3 (MT-3). Pb(2+) binds to zinc-replete Zn7MT-3 displacing each zinc ion with a similar change in free energy (ΔG) and enthalpy (ΔH). EDTA chelation measurements of Zn7MT-3 and Pb7MT-3 reveal that both metal ions are extracted in a tri-phasic process, indicating that they bind to the protein in three populations with different binding thermodynamics. Metal binding is entropically favoured, with an enthalpic penalty that reflects the enthalpic cost of cysteine deprotonation accompanying thiolate ligation of the metal ions. These data indicate that Pb(2+) binding to both apo MT-3 and Zn7MT-3 is thermodynamically favourable, and implicate MT-3 in neuronal lead biochemistry.

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A study of the Pb(II) binding to recombinant mouse Zn7-metallothionein 1 and its domains by ESI TOF MS

Cited by 14 publications

References 20 publications

Cigarette Smoking during Pregnancy: Effects on Antioxidant Enzymes, Metallothionein and Trace Elements in Mother-Newborn Pairs

Cigarette Smoking during Pregnancy: Effects on Antioxidant Enzymes, Metallothionein and Trace Elements in Mother-Newborn Pairs

pH-Dependent Coordination of Pb²⁺ to Metallothionein2: Structures and Insight into Lead Detoxification

Thermodynamics of Pb(ii) and Zn(ii) binding to MT-3, a neurologically important metallothionein

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A study of the Pb(II) binding to recombinant mouse Zn7-metallothionein 1 and its domains by ESI TOF MS

Cited by 14 publications

References 20 publications

Cigarette Smoking during Pregnancy: Effects on Antioxidant Enzymes, Metallothionein and Trace Elements in Mother-Newborn Pairs

Cigarette Smoking during Pregnancy: Effects on Antioxidant Enzymes, Metallothionein and Trace Elements in Mother-Newborn Pairs

pH-Dependent Coordination of Pb2+ to Metallothionein2: Structures and Insight into Lead Detoxification

Thermodynamics of Pb(ii) and Zn(ii) binding to MT-3, a neurologically important metallothionein

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pH-Dependent Coordination of Pb²⁺ to Metallothionein2: Structures and Insight into Lead Detoxification