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

Rózga, Małgorzata; Sokołowska, Magdalena; Protas, Anna Maria; Bal, Wojciech

doi:10.1007/s00775-007-0244-8

Cited by 135 publications

(180 citation statements)

References 44 publications

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“…Moreover, human serum albumin (HSA) containing a DAHK motive has a lower affinity than DAHK, [32,34] and hence GHK is perhaps a stronger Cu 2+ chelator than HSA [40]. Moreover, the present measurements confirm clearly that either DAHK or GHK are much stronger Cu 2+ chelators by at least an order of magnitude than the peptide Aβ at pH 7.4.…”

Section: Resultssupporting

confidence: 60%

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Thermodynamic study of Cu2+ binding to the DAHK and GHK peptides by isothermal titration calorimetry (ITC) with the weaker competitor glycine

et al. 2011

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The peptides Asp-Ala-His-Lys (DAHK) and Gly-His-Lys (GHK) are naturally occurring copper(II)-chelating motives in human serum and cerebrospinal fluid. Here the sensitive thermodynamic technique isothermal titration calorimetry (ITC) has been used to study the energetics of copper(II) binding to DAHK and GHK peptides in the presence of the weaker ligand glycine as a competitor. DAHK and GHK bind Cu(II) predominantly in a 1:1 stoichiometry with conditional dissociation constants (i.e. at pH 7.4, in the absence of the competing chelators glycine and HEPES buffer) of 2.6 +/-0.4 x 10 -14 M and of 7.0 +/-1.0 x 10 -14 M, respectively. Furthermore, the apparent ΔH values were measured and the number of protons released upon Cu(II) binding was determined by performing experiments in different buffers. This allowed us to determine the conditional ΔG, ΔH, and ΔS, i.e. corrected for the contributions of the weaker ligand glycine and the buffer at pH 7.4. We found that the entropic and enthalpic contributions to the Cu(II)-binding to GHK and DAHK are distinct, with a higher enthalpic contribution for GHK. The obtained thermodynamic parameters correspond well to those in the literature obtained by other techniques, suggesting that the use of the weaker ligand glycine as a competitor in ITC provides accurate data for Cu(II)-binding to high affinity peptides, which cannot be accurately determined without the use of a competitor ligand.3

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Section: Resultssupporting

confidence: 60%

“…The reported conditional dissociation constant of GHK and analogues of DAHK are about 1 x 10 -14 M [19,20,[31][32][33][34][35][36]. Although in a 100mM HEPES buffer the affinity will decrease to a app Kd of about 10 -12 M at pH 7.4 [26], this affinity is still too high to be measured directly by ITC.…”

Section: Resultsmentioning

confidence: 97%

Thermodynamic study of Cu2+ binding to the DAHK and GHK peptides by isothermal titration calorimetry (ITC) with the weaker competitor glycine

et al. 2011

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“…This bears a striking resemblance to the Cu 2ϩ binding motif (NH 2 -XXH) at the N terminus of human serum albumin (HSA) (40,41). This site is responsible for Cu 2ϩ transport in blood plasma (42) and has a tight 1.0 pM affinity for Cu 2ϩ , whereas N-terminal tripeptide models possess a subpicomolar affinity (43)(44)(45)(46).…”

mentioning

confidence: 99%

Truncated Amyloid-β(11–40/42) from Alzheimer Disease Binds Cu2+ with a Femtomolar Affinity and Influences Fiber Assembly

Barritt

Viles

2015

Journal of Biological Chemistry

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Background: N-terminally truncated A␤ (11-40/42) typically constitutes 19% of plaque load in Alzheimer patients. Results: Cu 2ϩ binds to A␤ with a 34-fM dissociation constant and stabilizes very short highly amyloidogenic amyloid rods into longer A␤ fibers. Concussion: The very tight affinity explains the high levels of Cu 2ϩ in amyloid plaques. Significance: Copper, tightly bound to A␤ (11-40/42) , may influence disease pathology.

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“…Taking advantage of the Jahn-Teller effect, the d 8 and d 9 ions Ni 2+ and Cu 2+ show a distinct preference for the square-planar geometry provided by the ATCUN motif [22,30,31]. This binding mode involves the unprotonated terminal amino group and the imidazole side-chain of His3, and requires the deprotonation of two backbone amides.…”

Section: Introductionmentioning

confidence: 99%

Fatty Acid-Mediated Inhibition of Metal Binding to the Multi-Metal Site on Serum Albumin: Implications for Cardiovascular Disease

Blindauer

Khazaipoul²,

Yu³

et al. 2016

CTMC

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(2016) Fatty acid-mediated inhibition of metal binding to the multi-metal site on serum albumin : implications for cardiovascular disease. Current Trends in Medicinal Chemistry, 16. Permanent WRAP URL:http://wrap.warwick.ac.uk/78963 Copyright and reuse:The Warwick Research Archive Portal (WRAP) makes this work by researchers of the University of Warwick available open access under the following conditions. Copyright © and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable the material made available in WRAP has been checked for eligibility before being made available.Copies of full items can be used for personal research or study, educational, or not-for-profit purposes without prior permission or charge. Provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way.Publisher's statement: © Bentham Science Publishers. http://dx.doi.org/10.2174/1568026616666160216155927 A note on versions:The version presented here may differ from the published version or, version of record, if you wish to cite this item you are advised to consult the publisher's version. Please see the 'permanent WRAP URL' above for details on accessing the published version and note that access may require a subscription. Abstract: Human serum albumin (HSA) is the major protein in blood plasma and is responsible for circulatory transport of a range of small molecules including fatty acids, metal ions and drugs. We previously identified the major plasma Zn 2+ transport site on HSA and revealed that fatty-acid binding (at a distinct site called the FA2 site) and Zn 2+ binding are interdependent via an allosteric mechanism. Since binding affinities of long-chain fatty acids exceed those of plasma Zn 2+ , this means that under certain circumstances the binding of fatty acid molecules to HSA is likely to diminish HSA Zn 2+ -binding, and hence affects the control of circulatory and cellular Zn 2+ dynamics. This relationship between circulatory fatty acid and Zn 2+ dynamics is likely to have important physiological and pathological implications, especially since it has been recognised that Zn 2+ acts as a signalling agent in many cell types. Fatty acid levels in the blood are dynamic, but most importantly, chronic elevation of plasma fatty acid levels is associated with some metabolic disorders and disease states -including myocardial infarction and other cardiovascular diseases. In this article, we briefly review the metalbinding properties of albumin and highlight the importance of their interplay with fatty acid binding. We also consider the impact of this dynamic link upon levels and speciation of plasma Zn 2+ , its effect upon cellular Zn 2+ homeostasis and its relevance to cardiovascular and circulatory processes in health and disease.

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

Cited by 135 publications

References 44 publications

Thermodynamic study of Cu2+ binding to the DAHK and GHK peptides by isothermal titration calorimetry (ITC) with the weaker competitor glycine

Thermodynamic study of Cu2+ binding to the DAHK and GHK peptides by isothermal titration calorimetry (ITC) with the weaker competitor glycine

Truncated Amyloid-β(11–40/42) from Alzheimer Disease Binds Cu2+ with a Femtomolar Affinity and Influences Fiber Assembly

Fatty Acid-Mediated Inhibition of Metal Binding to the Multi-Metal Site on Serum Albumin: Implications for Cardiovascular Disease

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