Skip to content

Research at St Andrews

Structure, properties, and engineering of the major zinc binding site on human albumin

Research output: Contribution to journalArticle

DOI

Author(s)

CA Blindauer, I Harvey, KE Bunyan, Alan James Stewart, D Sleep, David James Harrison, S Berezenko, PJ Sadler

School/Research organisations

Abstract

Most blood-plasma zinc is bound to albumin, but the structure of the binding site has not been determined. Zn K-edge EXAFS spectroscopy and modeling studies show that the major Zn site on albumin is 5-coordinate with average Zn-O/N distances of 1.98 Angstroms and a weak 6th O/N bond of 2.48 Angstroms, consistent with coordination to His67 and Asn99 from domain-I, His247 and Asp249 from domain-II (residues conserved in all sequenced mammalian albumins), plus a water ligand. The dynamics of the domain-I/II interface, thought to be important to biological function, are affected by Zn2+ binding, which induces cooperative allosteric effects related to those of the pH-dependent Neutral-to-Base (N-to-B) transition. N99D/H mutations enhance Zn binding, but alter protein stability, whereas mutation of His67 to alanine removes an interdomain H-bond and weakens Zn2+ binding. Both wild-type and mutant albumins promote the safe management of high micromolar zinc concentrations for cells in cultures.
Close

Details

Original languageEnglish
Pages (from-to)23116-23124
Number of pages9
JournalJournal of Biological Chemistry
Volume284
DOIs
Publication statusPublished - 21 Aug 2009

    Research areas

  • Human-serum-albumin, Nuclear-magnetic-resonance, To-base transition, Crystal-structure, Metal-binding, Conformational-change, Equilibrium dialysis, In-vitro, Protein, Acid

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Reduced plasma magnesium levels in type-1 diabetes associate with prothrombotic changes in fibrin clotting and fibrinolysis

    Sobczak, A. I. S., Phoenix, F. A., Pitt, S. J., Ajjan, R. A. & Stewart, A. J., 3 Jan 2020, In : Thrombosis and Haemostasis. eFirst, 10 p.

    Research output: Contribution to journalArticle

  2. Coagulatory defects in type-1 and type-2 diabetes

    Sobczak, A. I. S. & Stewart, A. J., 16 Dec 2019, In : International Journal of Molecular Sciences. 20, 24, 28 p., 6345.

    Research output: Contribution to journalReview article

  3. The X files: ''The mystery of X chromosome instability in Alzheimer's disease''

    Bajic, V. P., Essak, M., Zivkovic, L., Stewart, A. J., Zafirovic, S., Bajic, V., Gojobori, T., Isenovic, E. & Spremo-Potparevic, B., 13 Dec 2019, (Accepted/In press) In : Frontiers in Genetics.

    Research output: Contribution to journalReview article

  4. Evaluation of the dual mTOR/PI3K inhibitors Gedatolisib (PF-05212384) and PF-04691502 against ovarian cancer xenograft models

    Langdon, S. P., Kay, C., Um, I. H., Muir, M., Sellar, G., Kan, J., Gourley, C. & Harrison, D. J., 10 Dec 2019, In : Scientific Reports. 9, 9 p., 18742.

    Research output: Contribution to journalArticle

  5. A metalloproteomic analysis of interactions between plasma proteins and zinc: elevated fatty acid levels affect zinc distribution

    Coverdale, J. P. C., Barnett, J. P., Adamu, A. H., Griffiths, E. J., Stewart, A. J. & Blindauer, C. A., 1 Nov 2019, In : Metallomics. 11, 11, p. 1805-1819 15 p.

    Research output: Contribution to journalArticle

Related by journal

  1. Combining SPR with atomic-force microscopy enables singlemolecule insights into activation and suppression of the complement cascade

    Makou, E., Bailey, R. G., Johnston, H., Parkin, J. D., Hulme, A. N., Hähner, G. & Barlow, P. N., 27 Dec 2019, In : Journal of Biological Chemistry. 294, 52, p. 20148-20163 16 p.

    Research output: Contribution to journalArticle

  2. Dysregulated Zn2+ homeostasis impairs cardiac type-2 ryanodine receptor and mitsugumin 23 functions, leading to sarcoplasmic reticulum Ca2+ leakage

    Reilly-O'Donnell, B., Robertson, G. B., Karumbi, A., McIntyre, C., Bal, W., Nishi, M., Takeshima, H., Stewart, A. J. & Pitt, S. J., 11 Aug 2017, In : Journal of Biological Chemistry. 292, 32, p. 13361-13373 13 p.

    Research output: Contribution to journalArticle

  3. The major histocompatibility complex class I immunopeptidome of extracellular vesicles

    Synowsky, S. A., Shirran, S. L., Cooke, F. G. M., Antoniou, A. N., Botting, C. H. & Powis, S. J., 13 Oct 2017, In : Journal of Biological Chemistry. 292, p. 17084-17092

    Research output: Contribution to journalArticle

  4. Response to Qian and Colvin: zinc-mediated regulation of the cardiac ryanodine receptor occurs via multiple binding sites

    Woodier, J., Rainbow, R. D., Stewart, A. J. & Pitt, S. J., 19 Feb 2016, In : Journal of Biological Chemistry. 291, 8, p. 4267

    Research output: Contribution to journalLetter

  5. Using a genetically encoded sensor to identify inhibitors of Toxoplasma gondii Ca2+ Signalling

    Sidik, S. M., Hortua Triana, M. A., Paul, A. S., El Bakkouri, M., Hackett, C. G., Tran, F., Westwood, N. J., Hui, R., Zuercher, W. J., Duraisingh, M. T., Moreno, S. N. J. & Lourido, S., 29 Apr 2016, In : Journal of Biological Chemistry. 291, 18, p. 9566-9580 15 p.

    Research output: Contribution to journalArticle

Related by journal

  1. Journal of Biological Chemistry (Journal)

    Simon John Powis (Member of editorial board)
    1 Jun 2015

    Activity: Publication peer-review and editorial work typesEditor of research journal

  2. Journal of Biological Chemistry (Journal)

    Terry K Smith (Member of editorial board)
    2006 → …

    Activity: Publication peer-review and editorial work typesPeer review of manuscripts

ID: 448542

Top