Probing a Homoleptic PbS<sub>3</sub> Coordination Environment in a Designed Peptide Using <sup>207</sup>Pb NMR Spectroscopy: Implications for Understanding the Molecular Basis of Lead Toxicity

Neupane, Kosh P.; Pecoraro, Vincent L.

doi:10.1002/anie.201004429

Cited by 38 publications

(24 citation statements)

References 45 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 207 Pb NMR resonance observed for solution A* at 2858 ppm is comparable to the signal reported earlier by Pecoraro and coworkers at δ( 207 Pb) = 2806 ppm for a Pb(II) bound coiled-coil peptide Pb 2 (GrandL12AL16L26C) 3 2−. 65 …”

Section: Discussionsupporting

confidence: 85%

See 1 more Smart Citation

Similarities between N-Acetylcysteine and Glutathione in Binding to Lead(II) Ions

Sisombath

Jalilehvand

2015

Chem. Res. Toxicol.

View full text Add to dashboard Cite

N -acetylcysteine is a natural thiol-containing antioxidant, a precursor for cysteine and glutathione, and a potential detoxifying agent for heavy metal ions. However, previous accounts of the efficiency of N-acetylcysteine (H2NAC) in excretion of lead are few and contradicting. Here we report results on the nature of lead(II) complexes formed with N-acetylcysteine in aqueous solution, which were obtained by combining information from several spectroscopic methods, including 207Pb, 13C and 1H NMR, Pb LIII-edge X-ray absorption, Ultraviolet-visible (UV-vis.) spectroscopy and electro-spray ionization mass spectrometry (ESI-MS). Two series of solutions were used containing CPb(II) = 10 and 100 mM, respectively, varying the H2NAC / Pb(II) mole ratios from 2.1 to 10.0 at pH = 9.1 – 9.4. The coordination environments obtained resemble those previously found for the Pb(II) glutathione system: at a ligand-to-lead mole ratio of 2.1 dimeric or oligomeric Pb(II) N-acetylcysteine complexes are formed, while a tri-thiolate [Pb(NAC)3]4− complex dominates in solutions with H2NAC/Pb(II) mole ratios > 3.0.

show abstract

Section: Discussionsupporting

confidence: 85%

“…68 The 207 Pb chemical shift for 1.0 M Pb(NO 3 ) 2 in D 2 O solution appears at −2990 ppm at room temperature, as reported by the Pecoraro group. 65, 66 In the present work, we have re-calibrated our previously reported 207 Pb NMR chemical shifts, which are now referred to the resonance at −2961 ppm of a 1.0 M Pb(NO 3 ) 2 aqueous solution.…”

Section: Resultsmentioning

confidence: 99%

Similarities between N-Acetylcysteine and Glutathione in Binding to Lead(II) Ions

Sisombath

Jalilehvand

2015

Chem. Res. Toxicol.

View full text Add to dashboard Cite

show abstract

“…This trigonal planar geometry had been suggested for Cd(II) bound CmtR. 52 While other metals bound to the (TRIL16 L C) 3 as a single species in well-defined geometries at pH above 8 7,10,14,20 , Cd(II)(TRIL16 L C) 3 − was observed to be a 40:60 mixture between 3-coordinate Cd(II)S 3 and 4-coordinate Cd(II)S 3 O (O from an exogenous water ligand) 14 .…”

Section: Introductionmentioning

confidence: 64%

“…The trimer aggregation is stabilized through salt bridge interactions between e and g residues at pH values above 5.5. Substitution of Leu with Cys in the sixteenth position of the sequence, yielding (TRIL16 L C) 3 (subscripted L indicating L-configuration of the residue), provides a tris-thiolate environment capable of binding soft metals such as Cd(II), Hg(II), Pb(II), As(III) and Bi(III) 6–20,1,26–28 These designed constructs can address important biochemical issues of metal-protein relationships and provide needed information on the metal binding and structural preferences in proteins. Moreover, incorporation of unnatural amino acids into a de Novo scaffold is possible.…”

Section: Introductionmentioning

confidence: 99%

d‐Cysteine Ligands Control Metal Geometries within De Novo Designed Three‐Stranded Coiled Coils

Ruckthong

Peacock

Pascoe

et al. 2017

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

While metal ion binding to naturally occurring L-amino acid proteins is well documented, understanding the impact of the opposite chirality (D) amino acids on the structure and stereochemistry of metals is in its infancy. We examine the effect of a D-configuration cysteine within a designed L-amino acid three-stranded coiled coil in order to enforce a precise coordination number on a metal center. The D-chirality does not alter the native fold, but the side-chain reorientation modifies the sterics of the metal binding pocket. L-Cys side-chains within the coiled-coil have previously been shown to rotate substantially from their preferred positions in the apo structure to create a binding site for a tetra-coordinate metal ion. However, here we show by x-ray crystallography that D-Cys side chains are pre-organized with suitable geometry to bind such a ligand. This is confirmed by comparison of the Zn(II)Cl(CSL16DC)32− to the published Zn(II)(H2O)(GRAND-CSL12AL16LC)3−1. Moreover, spectroscopic analysis indicates that the Cd(II) geometry observed using L-Cys ligands (a mixture of 3- and 4- coordinate Cd(II)) is altered to a single 4-coordinate specie when D-Cys is present. This work opens a new avenue for the control of metal site environment in man-made proteins, by simply altering the binding ligand with its mirror imaged D-configuration. Thus, the use of non-coded amino acids in a metal’s coordination sphere promises to be a powerful tool for controlling the properties of future metalloproteins.

show abstract

“…[17] These metallopeptides have served as excellent structural models for the metalloregulatory proteins such as MerR, CmtR, and ArsR. [18] Peptides containing two Cys substitutions lacking intervening leucines between the sulfurs in the heptad (TRIL9CL12C) formed Hg II complex with similar spectral features that resembles the structure of the metal center of Hg II -bound rubredoxin.…”

Section: Introductionmentioning

confidence: 99%

Probing the Coordination Environment of the Human Copper Chaperone HAH1: Characterization of Hg^II‐Bridged Homodimeric Species in Solution

Łuczkowski

Zeider

Hinz

et al. 2013

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

While metal ion homeostasis in cells is often mediated through metallochaperones, there are opportunities for toxic metals to be sequestered through the existing transport apparatus. Proper trafficking of CuI in human cells is partially achieved through complexation by HAH1, the human metallochaperone responsible for copper delivery to the Wilson and Menkes ATPase located in the trans-Golgi apparatus. In addition to binding copper, HAH1 strongly complexes HgII, with the x-ray structure of this complex previously described. We felt it was important to clarify the solution behavior of these systems and, therefore, have probed the binding of HgII to HAH1 over the pH range 7.5 to 9.4 using 199Hg NMR, 199mPAC and UV-visible spectroscopies. We have also examined the metal-dependent protein association over this pH range using analytical gel-filtration. We conclude that at pH 7.5, HgII is bound to a monomeric HAH1 as a two coordinate, linear complex (HgS2), like the HgII-Atx1 X-ray structure (PDB ID: 1CC8). At pH 9.4, HgII promotes HAH1 association, leading to formation of HgS3 and HgS4 complexes, which are in exchange on the μs-ns time scale. Thus, we have characterized structures that may represent central intermediates in the process of metal ion transfer, as well as their exchange kinetics.

show abstract

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

Cited by 38 publications

References 45 publications

Similarities between N-Acetylcysteine and Glutathione in Binding to Lead(II) Ions

Similarities between N-Acetylcysteine and Glutathione in Binding to Lead(II) Ions

d‐Cysteine Ligands Control Metal Geometries within De Novo Designed Three‐Stranded Coiled Coils

Probing the Coordination Environment of the Human Copper Chaperone HAH1: Characterization of Hg^II‐Bridged Homodimeric Species in Solution

Contact Info

Product

Resources

About

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

Cited by 38 publications

References 45 publications

Similarities between N-Acetylcysteine and Glutathione in Binding to Lead(II) Ions

Similarities between N-Acetylcysteine and Glutathione in Binding to Lead(II) Ions

d‐Cysteine Ligands Control Metal Geometries within De Novo Designed Three‐Stranded Coiled Coils

Probing the Coordination Environment of the Human Copper Chaperone HAH1: Characterization of HgII‐Bridged Homodimeric Species in Solution

Contact Info

Product

Resources

About

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

Probing the Coordination Environment of the Human Copper Chaperone HAH1: Characterization of Hg^II‐Bridged Homodimeric Species in Solution