The Sub‐picomolar Cu<sup>2+</sup> Dissociation Constant of Human Serum Albumin

Bossak-Ahmad, Karolina; Frączyk, Tomasz; Bal, Wojciech; Drew, Simon C.

doi:10.1002/cbic.201900435

Cited by 39 publications

(66 citation statements)

References 27 publications

(34 reference statements)

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“…Baseline correction was performed by weighted subtraction of the spectrum obtained using a water blank. Spectral simulations were carried out as previously described [ 51 ].…”

Section: Methodsmentioning

confidence: 99%

Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate

Bossak-Ahmad

Wiśniewska

Bal

et al. 2020

IJMS

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The tripeptide NH2–Gly–His–Lys–COOH (GHK), cis-urocanic acid (cis-UCA) and Cu(II) ions are physiological constituents of the human body and they co-occur (e.g., in the skin and the plasma). While GHK is known as Cu(II)-binding molecule, we found that urocanic acid also coordinates Cu(II) ions. Furthermore, both ligands create ternary Cu(II) complex being probably physiologically functional species. Regarding the natural concentrations of the studied molecules in some human tissues, together with the affinities reported here, we conclude that the ternary complex [GHK][Cu(II)][cis-urocanic acid] may be partly responsible for biological effects of GHK and urocanic acid described in the literature.

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“…Baseline correction was performed by weighted subtraction of the spectrum obtained using a water blank. Spectral simulations were carried out as previously described [ 51 ].…”

Section: Methodsmentioning

confidence: 99%

Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate

Bossak-Ahmad

Wiśniewska

Bal

et al. 2020

IJMS

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“…To which extent they are bound to Cu(II) in nature is not clear. One well established case is human serum albumin which has a XZH motif with a K D of 10 −13 M [9]. Serum albumin in humans is only loaded to a few % with Cu, indicating that these motifs may be able to bind Cu(II) in vivo [10].…”

Section: Introductionmentioning

confidence: 99%

Copper-binding motifs Xxx-His or Xxx-Zzz-His (ATCUN) linked to an antimicrobial peptide: Cu-binding, antimicrobial activity and ROS production

Bouraguba

Glattard

Naudé

et al. 2020

Journal of Inorganic Biochemistry

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Depending on the coordination, copper ions can have a very high activity in catalyzing the production of reactive oxygen species. Thus interest arose in increasing the activity of antimicrobial peptides (AMPs) by equipping them with a Cu-binding unit. Several examples, native and engineered, have been investigated with the motif Xxx-Zzz-His, called Amino Terminal Cu(II)-and Ni(II)-binding (ATCUN) motif. Here we investigate a short AMP that was equipped either with Xxx-Zzz-His or Xxx-His. Xxx-His is a shorter motif and yields a more redox active copper complex. The control AMP, Xxx-His-AMP and Xxx-Zzz-His-AMP were investigated toward Cu-binding, Reactive Oxygen Species (ROS) production and antimicrobial activity in E. coli. The data indicate that these Cu-binding motifs have very limited impact on antimicrobial activity and low ROS production capability.

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“…Cu(II)-binding properties of NTS have been in the focus of intensive studies. The dissociation constant (K D ) values for Cu(II) in NTS of HSA (Asp-Ala-His) and of bovine serum albumin (Asp-Thr-His), have been determined by a variety of methods such as potentiometric titration, equilibrium dialysis, ultrafiltration, isothermal titration calorimetry, Cu(II) electrode and several spectroscopic methods, including EPR 27 . However, the estimated values for the conditional dissociation constant vary from picomolar (log K D = −11.18) to subfemtomolar (log K D = −16.18) range 28,23 .…”

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Copper(II)-binding equilibria in human blood

Kirsipuu

Zadorožnaja

Smirnova

et al. 2020

Sci Rep

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Vello tõugu 1 & peep palumaa 1* it has been reported that cu(ii) ions in human blood are bound mainly to serum albumin (HSA), ceruloplasmin (CP), alpha-2-macroglobulin (α2M) and His, however, data for α2M are very limited and the thermodynamics and kinetics of the copper distribution are not known. We have applied a new LC-ICP MS-based approach for direct determination of Cu(II)-binding affinities of HSA, CP and α2M in the presence of competing Cu(II)-binding reference ligands including His. The ligands affected both the rate of metal release from Cu•HSA complex and the value of K D. Slow release and K D = 0.90 pM was observed with nitrilotriacetic acid (NTA), whereas His showed fast release and substantially lower K D = 34.7 fM (50 mM HEPES, 50 mM NaCl, pH 7.4), which was explained with formation of ternary His•cu•HSA complex. High mM concentrations of EDTA were not able to elicit metal release from metallated CP at pH 7.4 and therefore it was impossible to determine the K D value for CP. In contrast to earlier inconclusive evidence, we show that α2M does not bind Cu(II) ions. In the human blood serum ~75% of Cu(II) ions are in a nonexchangeable manner bound to CP and the rest exchangeable copper is in an equilibrium between HSA (~25%) and Cu(II)-His-Xaa ternary complexes (~0.2%).

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

Cited by 39 publications

References 27 publications

Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate

Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate

Copper-binding motifs Xxx-His or Xxx-Zzz-His (ATCUN) linked to an antimicrobial peptide: Cu-binding, antimicrobial activity and ROS production

Copper(II)-binding equilibria in human blood

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

Cited by 39 publications

References 27 publications

Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate

Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate

Copper-binding motifs Xxx-His or Xxx-Zzz-His (ATCUN) linked to an antimicrobial peptide: Cu-binding, antimicrobial activity and ROS production

Copper(II)-binding equilibria in human blood

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