Preparation and X-ray characterization of two-coordinate Cu(I) complex of aliphatic thiolato ligand: Effect of steric bulk on coordination features

Kohner-Kerten, Amir; Tshuva, Edit Y.

doi:10.1016/j.jorganchem.2008.03.002

Cited by 18 publications

(17 citation statements)

References 31 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Shurki and co-workers 35 developed a quantitative method to predict copper coordination number in small thiolato complexes, 36 using ligands resembling the Cys residues found in Atox1. 41 Their calculations on Atox1 as a model protein showed that the most favorable state is two-coordinated. However, in this case, they relied on an Atox1 monomeric NMR structure, and in order to simulate the three-coordinated state they added an external "cysteine-like" ligand.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Their calculations were performed in both vacuum and aqueous solution but did not take into account the effect of the protein environment. Shurki and co-workers developed a quantitative method to predict copper coordination number in small thiolato complexes, using ligands resembling the Cys residues found in Atox1 . Their calculations on Atox1 as a model protein showed that the most favorable state is two-coordinated.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cu(I) Controls Conformational States in Human Atox1 Metallochaperone: An EPR and Multiscale Simulation Study

et al. 2020

View full text Add to dashboard Cite

Atox1 is a human copper metallochaperone that is responsible for transferring copper ions from the main human copper transporter, hCtr1, to ATP7A/B in the Golgi apparatus. Atox1 interacts with the Ctr1 C-terminal domain as a dimer, although it transfers the copper ions to ATP7A/B in a monomeric form. The copper binding site in the Atox1 dimer involves Cys12 and Cys15, while Lys60 was also suggested to play a role in the copper binding. We recently showed that Atox1 can adopt various conformational states, depending on the interacting protein. In the current study, we apply EPR experiments together with hybrid quantum mechanics–molecular mechanics molecular dynamics simulations using a recently developed semiempirical density functional theory approach, to better understand the effect of Atox1’s conformational states on copper coordination. We propose that the flexibility of Atox1 occurs owing to protonation of one or more of the cysteine residues, and that Cys15 is an important residue for Atox1 dimerization, while Cys12 is a critical residue for Cu(I) binding. We also show that Lys60 electrostatically stabilizes the Cu(I)–Atox1 dimer.

show abstract

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cu(I) Controls Conformational States in Human Atox1 Metallochaperone: An EPR and Multiscale Simulation Study

et al. 2020

View full text Add to dashboard Cite

show abstract

“…As a continuation to this study, Cu(I) complexes were synthesized using small aliphatic thiolato ligands as more accurate models to the cysteine amino acid. 44 The ligands employed were iso-propylthiol and tert-butylthiol. Although all attempts to obtain a mononuclear complex from the iso-propylthiolato ligand failed, the tert-butylthiolato ligand gave a mononuclear di-coordinate complex under specific reaction conditions (Fig.…”

Section: Small-molecule Based Modelsmentioning

confidence: 99%

“…8 ORTEP structure at 50% probability ellipsoids of a mononuclear Cu(I) anionic di-coordinate complex of the aliphatic ligand tert-butylthiol. 44 Fig. 9 A tri-coordinate model based on thiolato ligands.…”

Section: Small-molecule Based Modelsmentioning

confidence: 99%

The MXCXXC class of metallochaperone proteins: model studies

Shoshan

Tshuva

2011

Chem. Soc. Rev.

Self Cite

View full text Add to dashboard Cite

Transition metal ions can be both beneficial and harmful to biological systems if not carefully regulated. A family of proteins that include a conserved sequence in their binding site of MXCXXC is responsible for delivery and homeostasis of different metals. Model studies present an effective tool for studying the parameters governing metal affinity, selectivity and other mechanistic aspects. Small-molecule, peptide-based, and advanced models will be presented, as well as functional models of potential industrial applications.

show abstract

“…The mononuclear two coordinate Cu(I) complex as a structural model of the active site of copper metallochaperone proteins was reported [81]. Metal-peptide conjugates containing bis(picolyl)amine were suggested as artificial metallochaperones because they have the potential to deliver metal ions to specific compartments in the cell as determined by the peptide moieties [82].…”

Section: Recent Aspects Of Copper Chaperonesmentioning

confidence: 99%

Metallochaperones - an Overview

Sekhon¹

2010

curr chem biol

View full text Add to dashboard Cite

Improper allocation of the incorrect metal ion to a metalloprotein can have resounding and often detrimental effects on different aspects of cellular physiology. Enzymes that employ transition metals as co-factors are housed in a wide variety of intracellular locations or are exported to the extracellular milieu. Metallochaperones (much smaller than the cell) are essential for the proper functioning of cells and are a distinct class of proteins which accounts for the incorporation of metal ion cofactors into metalloenzymes / metalloproteins. Metals in the cells are distributed by metallochaperones (intracellular metal ion carriers) and these intracellular metal ion carriers ensure that the correct metal is acquired by a specific metalloenzyme. Metallochaperones act in the intracellular trafficking of metal ions to protect the cell and are a family of soluble metal receptor proteins that bind and protect metal ions/cofactors. The target sites for metal/cofactor delivery include a number of metalloenzymes, or proteins that bind metal ions and use these ions as cofactors to perform essential biochemical reactions such as cellular respiration, DNA synthesis and antioxidant defense. In this review, metallochaperones for various metals such as copper, nickel, zinc, iron, arsenic, manganese, cobalt, molybdenum and vanadium are discussed. In the cell, the specific metal ion is often selected by specific protein-protein interactions between the apoprotein and a metallochaperone and ligand-exchange reactions have been involved in the metal transfer from metallochaperones to cognate apoproteins. The development of chaperone-based medications from medicinal plants has been reported.

show abstract

Preparation and X-ray characterization of two-coordinate Cu(I) complex of aliphatic thiolato ligand: Effect of steric bulk on coordination features

Cited by 18 publications

References 31 publications

Cu(I) Controls Conformational States in Human Atox1 Metallochaperone: An EPR and Multiscale Simulation Study

Cu(I) Controls Conformational States in Human Atox1 Metallochaperone: An EPR and Multiscale Simulation Study

The MXCXXC class of metallochaperone proteins: model studies

Metallochaperones - an Overview

Contact Info

Product

Resources

About