The role of protonation and metal chelation preferences in defining the properties of mercury-binding coiled coils

Dieckmann, Gregg R.; McRorie, Donald K.; Lear, James D.; Sharp, Kim A.; DeGrado, William F.; Pecoraro, Vincent L.

doi:10.1006/jmbi.1998.1891

Cited by 119 publications

(201 citation statements)

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“…Transition metal ions have typical preferences for certain type of donor ligands, but also for coordination geometries [55]. In proteins and peptides, mercury(II) is known to have an outstanding affinity for the soft sulfur ligands and a strong preference for linear [56][57][58][59] or trigonal coordination geometries [59][60][61][62], however, it can also adopt a tetrahedral coordination environment of donor groups [63][64][65]. In contrast, cadmium(II) and zinc(II) prefer tetrahedral coordination geometry [55,59,65], but higher 15 coordination numbers are also easily possible, especially for the more flexible zinc(II) ions [55,66].…”

Section: Competition Of Zinc(ii) With Cadmium(ii) or Mercury(ii) In Bmentioning

confidence: 99%

Competition of zinc(II) with cadmium(II) or mercury(II) in binding to a 12-mer peptide

Jancsó

Gyurcsik

Mesterházy

et al. 2013

Journal of Inorganic Biochemistry

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Section: Competition Of Zinc(ii) With Cadmium(ii) or Mercury(ii) In Bmentioning

confidence: 99%

Competition of zinc(II) with cadmium(II) or mercury(II) in binding to a 12-mer peptide

Jancsó

Gyurcsik

Mesterházy

et al. 2013

Journal of Inorganic Biochemistry

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“…Work in our group involves the designed TRI and GRAND peptides based on the heptad repeat, L a K b A c L d E e E f K g , and derivatives thereof (12,13). These sequences (shown in Table 1) were designed to assemble in aqueous solution into ␣-helices, which aggregate to form 3-stranded coiled coils at pH values Ͼ5.5.…”

mentioning

confidence: 99%

“…Substitution of either an a or d Leu with Cys provides a preorganized homoleptic thiol site in the interior of these coiled coils. The binding of numerous heavy metals such as Hg(II), Bi(III), Pb(II), and As(III) has been explored (12)(13)(14)(15)(16)(17)(18)(19), although the most intriguing system has been Cd(II) that binds to TRIL16C as a mixture of 3-and 4-coordinate CdS 3 and CdS 3 O (O from an exogenous water molecule) forms, respectively.…”

mentioning

confidence: 99%

Using diastereopeptides to control metal ion coordination in proteins

Peacock

Hemmingsen

Pecoraro

2008

Proc. Natl. Acad. Sci. U.S.A.

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Here, we report a previously undescribed approach for controlling metal ion coordination geometry in biomolecules by reorientating amino acid side chains through substitution of L-to D-amino acids. These diastereopeptides allow us to manipulate the spatial orientation of amino acid side chains to alter the sterics of metal binding pockets. We have used this approach to design the de novo metallopeptide, Cd (TRIL12L DL16C)

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“…[19][20][21][33][34][35][36][37][38] These α-helical peptide families have heptad repeats of seven amino acid residues that contain hydrophobic leucine residues in the a (first) and d (fourth) positions (Table 1). [39] The resultant 3-SCC has all of the hydrophobic leucine residues packed on the interior of the 3-SCC and hydrophilic residues (e and g) on the exterior, forming salt bridges that stabilize the coiled coil.…”

mentioning

confidence: 99%

Probing a Homoleptic PbS₃ Coordination Environment in a Designed Peptide Using ²⁰⁷Pb NMR Spectroscopy: Implications for Understanding the Molecular Basis of Lead Toxicity

Neupane

Pecoraro

2010

Angewandte Chemie

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Lead is a ubiquitous environmental contaminant; nearly 5% of American children are affected by lead poisoning (a blood lead level (BLL) of 10 μgdL −1 or higher).[1] Even lower BLLs have been shown to cause many subtle health effects in children. Lead, which is found in paint and soil, causes toxicity by several possible mechanisms. Pb 2+ interacts with several zinc enzymes or proteins (such as carbonic anhydrase, acetylcholine esterase, Cys 2 His 2 "zinc-finger" proteins, and acid phophatases) [2,3] and calcium ion binding proteins (calmodulin, calbindin, and troponin C).[4] Inhibition of protein function is induced by alternative coordination number and structural preferences.[5,6] Pb 2+ is a chemically interesting toxin in that it can replace calcium and sometimes zinc in "hard" active sites that are oxygen/nitrogen rich; it can also attack softer ligands, such as all-sulfur-containing zinc ion coordination sites. Among the sulfur-rich targets for Pb 2+ are glutathione and metallothioneines, which cause perturbations of essential metal ion homeostasis.Aminolevulinic acid dehydratase (ALAD), a zinc-dependent enzyme, is inhibited by a femtomolar concentrations of Pb 2+ .[2] ALAD is found in yeast and mammals and is involved in the second step of heme biosynthesis. Pb 2+ -poisoned ALAD blocks the synthesis of hemoglobin, causing anemia in mammals. Furthermore, toxic levels of aminolevulinic acid can result. The crystal structure of ALAD contains an unusual Zn(Cys) 3 H 2 O site, where Zn 2+ is substituted by Pb 2+ in a trigonal pyramidal geometry. [7] The high affinity of Pb 2+ to cysteine thiolates is presumably due to the high enthalpy of Pb-S bond formation and the preferred PbS 3 coordination geometry in thiolate-rich sites of proteins.[8] A number of peptides[9-11] and small-molecule synthetic models [12] have been used to understand the chemistry of the Pb II -poisoned ALAD. UV/Vis and EXAFS studies on the metalloregulatory protein Pb-PbrR691 and Pb 2+ model compounds reveal that Pb 2+ binds in a PbS 3 environment. [13] Heteronuclear magnetic resonance spectroscopy with nuclei such as 43 Ca, 113 Cd, and 199 Hg has been a powerful tool for studying the active site structures of metalloenzymes and their model compounds. [14][15][16][17][18][19][20][21] Similarly, lead provides an NMR active nucleus ( 207 Pb, nuclear spin I = 1/2) with a natural abundance of 22.6% and a relatively good receptivity (11.7 times

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The role of protonation and metal chelation preferences in defining the properties of mercury-binding coiled coils

Cited by 119 publications

References 74 publications

Competition of zinc(II) with cadmium(II) or mercury(II) in binding to a 12-mer peptide

Competition of zinc(II) with cadmium(II) or mercury(II) in binding to a 12-mer peptide

Using diastereopeptides to control metal ion coordination in proteins

Probing a Homoleptic PbS₃ Coordination Environment in a Designed Peptide Using ²⁰⁷Pb NMR Spectroscopy: Implications for Understanding the Molecular Basis of Lead Toxicity

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The role of protonation and metal chelation preferences in defining the properties of mercury-binding coiled coils

Cited by 119 publications

References 74 publications

Competition of zinc(II) with cadmium(II) or mercury(II) in binding to a 12-mer peptide

Competition of zinc(II) with cadmium(II) or mercury(II) in binding to a 12-mer peptide

Using diastereopeptides to control metal ion coordination in proteins

Probing a Homoleptic PbS3 Coordination Environment in a Designed Peptide Using 207Pb NMR Spectroscopy: Implications for Understanding the Molecular Basis of Lead Toxicity

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Probing a Homoleptic PbS₃ Coordination Environment in a Designed Peptide Using ²⁰⁷Pb NMR Spectroscopy: Implications for Understanding the Molecular Basis of Lead Toxicity