The Cu(II) affinity of the N-terminus of human copper transporter CTR1: Comparison of human and mouse sequences

Bossak, Karolina; Drew, Simon C.; Stefaniak, Ewelina; Płonka, Dawid; Bonna, Arkadiusz; Bal, Wojciech

doi:10.1016/j.jinorgbio.2018.01.011

Cited by 30 publications

(34 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The spectrophotometric data fit well to the 1:1 ligand-to-metal binding isotherm (Figure S1) with dissociation constants of DAHK and NCtr1 for copper binding in our experimental conditions were found to be 5.16 ± 1.4 × 10 –12 and 7.42 ± 4.2 × 10 –9 M, respectively, which are close to reported values. 36,38,39 The dissociation constant for the ATSM ligand was found to be 7.7 ± 2.02 × 10 –15 M. Indeed, the ATSM ligand has more affinity to copper than ATCUN peptides. These data suggest that ATSM-Cu(II) remains stable in the presence of ATCUN motifs.…”

Section: Resultsmentioning

confidence: 95%

Does the ATSM-Cu(II) Biomarker Integrate into the Human Cellular Copper Cycle?

Walke

Ruthstein

2019

ACS Omega

View full text Add to dashboard Cite

Hypoxia is commonly encountered in the tumor microenvironment and drives proliferation, angiogenesis, and resistance to therapy. Imaging of hypoxia is important in many disease states in oncology, cardiology, and neurology. Finding clinically approved imaging biomarkers for hypoxia has proved challenging. Candidate biomarkers have shown low uptake into tumors and low signal to background ratios that adversely affect imaging quality. Copper complexes have been identified as potential biomarkers for hypoxia owing to their redox ability. Active uptake of copper complexes into cells could ensure selectivity and high sensitivity. We explored the reactivity and selectivity of the ATSM-Cu(II) biomarker to proteins that are involved in the copper cycle using electron paramagnetic resonance (EPR) spectroscopy and UV–vis measurements. We show that the affinity of the ATSM-Cu(II) complex to proteins in the copper cycle is low and the cell probably does not actively uptake ATSM-Cu(II).

show abstract

Section: Resultsmentioning

confidence: 95%

Does the ATSM-Cu(II) Biomarker Integrate into the Human Cellular Copper Cycle?

Walke

Ruthstein

2019

ACS Omega

View full text Add to dashboard Cite

show abstract

“…The MDH‐am tripeptide, a model of the N‐terminal site of hCtr1 binds Cu 2+ with a conditional log c

K \binom{Cu}{Cu (MDH)}

=13.1 at pH 7.4, and a longer peptide containing the first 14 residues has a comparable log c

K \binom{Cu}{Cu (Ctr 1 - 14)}

=13.0 . The revised conditional binding constant for HSA is therefore comparable with that for hCtr1.…”

Section: Figurementioning

confidence: 92%

The Sub‐picomolar Cu²⁺ Dissociation Constant of Human Serum Albumin

et al. 2019

Self Cite

View full text Add to dashboard Cite

The apparent affinity of human serum albumin (HSA) for divalent copper has long been the subject of great interest, due to its presumed role as the major Cu2+‐binding ligand in blood and cerebrospinal fluid. Using a combination of electronic absorption, circular dichroism and room‐temperature electron paramagnetic resonance spectroscopies, together with potentiometric titrations, we competed the tripeptide GGH against HSA to reveal a conditional binding constant of log cKCuCu(HSA) =13.02±0.05 at pH 7.4. This rigorously determined value of the Cu2+ affinity has important implications for understanding the extracellular distribution of copper.

show abstract

“…Noteworthy is the fact that, though both groups provide converging evidence on Cu 2+ binding to the MDH site, the stability constant values are much lower than those reported for Cu 2+ complexes with the high affinity N-terminus of human serum albumin (HSA) [ 31 ]. Perhaps the underestimation of some of these values results from neglecting the competition of the buffer [ 32 ]. The issue concerning the metal ion transfer from HSA to Ctr1 (1-14) has been overcome by recent investigations [ 17 , 32 ] reporting more reliable affinity values for the binding of Cu 2+ to Ctr1 (1-14) , which might account for the metal ion transfer from HSA.…”

Section: Introductionmentioning

confidence: 99%

A Deeper Insight in Metal Binding to the hCtr1 N-terminus Fragment: Affinity, Speciation and Binding Mode of Binuclear Cu2+ and Mononuclear Ag+ Complex Species

Magrı̀

Tabbı̀

Naletova

et al. 2022

IJMS

View full text Add to dashboard Cite

Ctr1 regulates copper uptake and its intracellular distribution. The first 14 amino acid sequence of the Ctr1 ectodomain Ctr1(1-14) encompasses the characteristic Amino Terminal Cu2+ and Ni2+ binding motif (ATCUN) as well as the bis-His binding motif (His5 and His6). We report a combined thermodynamic and spectroscopic (UV-vis, CD, EPR) study dealing with the formation of Cu2+ homobinuclear complexes with Ctr1(1-14), the percentage of which is not negligible even in the presence of a small Cu2+ excess and clearly prevails at a M/L ratio of 1.9. Ascorbate fails to reduce Cu2+ when bound to the ATCUN motif, while it reduces Cu2+ when bound to the His5-His6 motif involved in the formation of binuclear species. The histidine diade characterizes the second binding site and is thought to be responsible for ascorbate oxidation. Binding constants and speciation of Ag+ complexes with Ctr1(1-14), which are assumed to mimic Cu+ interaction with N-terminus of Ctr1(1-14), were also determined. A preliminary immunoblot assay evidences that the anti-Ctr1 extracellular antibody recognizes Ctr1(1-14) in a different way from the longer Ctr1(1-25) that encompasses a second His and Met rich domain.

show abstract

The Cu(II) affinity of the N-terminus of human copper transporter CTR1: Comparison of human and mouse sequences

Cited by 30 publications

References 47 publications

Does the ATSM-Cu(II) Biomarker Integrate into the Human Cellular Copper Cycle?

Does the ATSM-Cu(II) Biomarker Integrate into the Human Cellular Copper Cycle?

The Sub‐picomolar Cu²⁺ Dissociation Constant of Human Serum Albumin

A Deeper Insight in Metal Binding to the hCtr1 N-terminus Fragment: Affinity, Speciation and Binding Mode of Binuclear Cu2+ and Mononuclear Ag+ Complex Species

Contact Info

Product

Resources

About

The Cu(II) affinity of the N-terminus of human copper transporter CTR1: Comparison of human and mouse sequences

Cited by 30 publications

References 47 publications

Does the ATSM-Cu(II) Biomarker Integrate into the Human Cellular Copper Cycle?

Does the ATSM-Cu(II) Biomarker Integrate into the Human Cellular Copper Cycle?

The Sub‐picomolar Cu2+ Dissociation Constant of Human Serum Albumin

A Deeper Insight in Metal Binding to the hCtr1 N-terminus Fragment: Affinity, Speciation and Binding Mode of Binuclear Cu2+ and Mononuclear Ag+ Complex Species

Contact Info

Product

Resources

About

The Sub‐picomolar Cu²⁺ Dissociation Constant of Human Serum Albumin