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Human serum albumin coordinates Cu(II) at its N-terminal binding site with 1 pM affinity

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Abstract

The conditional stability constant at pH 7.4 for Cu(II) binding at the N-terminal site (NTS) of human serum albumin (HSA) was determined directly by competitive UV–vis spectroscopy titrations using nitrilotriacetic acid (NTA) as the competitor in 100 mM NaCl and 100 mM N-(2-hydroxyethyl)piperazine-N′-ethanesulfonic acid (Hepes). The log K cNTS value of 12.0 ± 0.1 was determined for HSA dissolved in 100 mM NaCl. A false log log K cNTS value of 11.4 ± 0.1 was obtained in the 100 mM Hepes buffer, owing to the formation of a ternary Cu(NTA)(Hepes) complex. The impact of the picomolar affinity of HSA for Cu(II) on the availability of these ions in neurodegenerative disorders is briefly discussed.

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Abbreviations

AD:

Alzheimer disease

BSA:

Bovine serum albumin

CD:

Circular dichroism

CSF:

Cerebrospinal fluid

EDTA:

Ethylenediaminetetraacetic acid

Hepes:

N-(2-Hydroxyethyl)piperazine-N′-ethanesulfonic acid

HSA:

Human serum albumin

MBS:

Multimetal binding site

NTA:

Nitrilotriacetic acid

NTS:

N-terminal site

PrP:

Prion protein

Tris:

Tris(hydroxymethyl)aminomethane

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Acknowledgement

This work was sponsored by the Polish Ministry of Education and Science, grant PBZ-KBN-124/P05/2004.

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Authors and Affiliations

  1. Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106, Warsaw, Poland

    Małgorzata Rózga, Anna Maria Protas & Wojciech Bal

  2. Department of Hygiene, Wrocław Medical University, Mikulicza-Radeckiego 7, 50-345, Wrocław, Poland

    Magdalena Sokołowska

  3. Central Institute for Labour Protection, National Research Institute, Czerniakowska 16, 00-701, Warsaw, Poland

    Wojciech Bal

Authors
  1. Małgorzata Rózga
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  2. Magdalena Sokołowska
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  3. Anna Maria Protas
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  4. Wojciech Bal
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Correspondence to Wojciech Bal.

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Rózga, M., Sokołowska, M., Protas, A.M. et al. Human serum albumin coordinates Cu(II) at its N-terminal binding site with 1 pM affinity. J Biol Inorg Chem 12, 913–918 (2007). https://doi.org/10.1007/s00775-007-0244-8

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  • DOI: https://doi.org/10.1007/s00775-007-0244-8

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