Skip to content

Research at St Andrews

Circulatory zinc transport is controlled by distinct interdomain sites on mammalian albumins

Research output: Contribution to journalArticle

DOI

Open Access permissions

Open

Author(s)

Katarzyna B. Handing, Ivan G Shabalin, Omar Kassaar, Siavash Khazaipoul, Claudia A Blindauer, Alan James Stewart, Maksymilian Chruszcz, Wladek Minor

School/Research organisations

Abstract

Zinc is an essential nutrient in the body; it is required for the catalytic activity of many hundreds of human enzymes and virtually all biological processes, therefore its homeostasis and trafficking is of crucial interest. Serum albumin is the major carrier of Zn2+ in the blood and is required for its systemic distribution. Here we present the first crystal structures of human serum albumin (HSA) and equine serum albumin (ESA) in complex with Zn2+. The structures allow unambiguous identification of the major zinc binding site on these two albumins, as well as several further, weaker zinc binding sites. The major site in both HSA and ESA has tetrahedral geometry and comprises three protein ligands from the sidechains of His67, His247 and Asp249 and a water molecule. Isothermal titration calorimetric studies of a HSA H67A mutant confirm this to be the highest affinity Zn2+ site. Furthermore, analysis of Zn2+ binding to HSA and ESA proved the presence of secondary sites with 20-50-fold weaker affinities, which may become of importance under particular physiological conditions. Both calorimetry and crystallography suggest that ESA possesses an additional site compared to HSA, involving Glu153, His157 and His288. The His157 residue is replaced by Phe in HSA, incapable of metal coordination. Collectively, these findings are critical to our understanding of the role serum albumin plays in circulatory Zn2+ handling and cellular delivery.
Close

Details

Original languageEnglish
Pages (from-to)6635-6648
Number of pages14
JournalChemical Science
Volume7
Issue number11
Early online date15 Aug 2016
DOIs
Publication statusPublished - 1 Nov 2016

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

View graph of relations

Related by author

  1. 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., 15 Oct 2019, In : Metallomics. Advance Article, p. 1-15 15 p.

    Research output: Contribution to journalArticle

  2. Plasma non-esterified fatty acids contribute to increased coagulability in type-2 diabetes through altered plasma zinc speciation

    Sobczak, A. I. S., Katundu, K. G. H., Phoenix, F. A., Khazaipoul, S., Yu, R., Lampiao, F., Stefanowicz, F., Blindauer, C. A., Pitt, S. J., Smith, T. K., Ajjan, R. A. & Stewart, A. J., 28 Aug 2019, In : biorxiv. 38 p.

    Research output: Contribution to journalArticle

  3. Changes in plasma free fatty acids associated with type-2 diabetes

    Sobczak, A. I. S., Blindauer, C. A. & Stewart, A. J., 28 Aug 2019, In : Nutrients. 11, 9, 42 p., 2022.

    Research output: Contribution to journalReview article

  4. Sub-micromolar pulse dipolar EPR spectroscopy reveals increasing CuII-labelling of double-histidine motifs with lower temperature

    Wort, J. L., Ackermann, K., Giannoulis, A., Stewart, A. J., Norman, D. G. & Bode, B. E., 19 Aug 2019, In : Angewandte Chemie - International Edition. 58, 34, p. 11681-11685 5 p.

    Research output: Contribution to journalArticle

  5. Sub-micromolar pulse dipolar EPR spectroscopy reveals increasing CuII-labelling of double-histidine motifs with lower temperature

    Wort, J., Ackermann, K., Giannoulis, A., Stewart, A. J., Norman, D. & Bode, B. E., 19 Aug 2019, In : Angewandte Chemie. 131, 34, p. 11807-11811 6 p.

    Research output: Contribution to journalArticle

Related by journal

  1. A natural solution to photoprotection and isolation of the potent polyene antibiotic, marinomycin A

    Bailey, C. S., Zarins-Tutt, J. S., Agbo, M., Gao, H., Diego-Taboada, A., Gan, M., Hamed Farghal, R. B., Abraham, E., Mackenzie, G., Evans, P. A. & Goss, R. J. M., 28 Aug 2019, In : Chemical Science. 10, 32, p. 7549-7553 5 p.

    Research output: Contribution to journalArticle

  2. Catalytic enantioselective synthesis of perfluoroalkyl-substituted β-lactones via a concerted asynchronous [2+2] cycloaddition: a synthetic and computational study

    Barrios Antunez, D-J., Greenhalgh, M. D., Brueckner, A. C., Walden, D. M., Elías-Rodríguez, P., Roberts, P., Young, B. G., West, T. H., Slawin, A. M. Z., Cheong, P. H-Y. & Smith, A. D., 28 Jun 2019, In : Chemical Science. 10, 24, p. 6162-6173 12 p.

    Research output: Contribution to journalArticle

  3. Hydrocarbon-soluble, hexaanionic fulleride complexes of magnesium

    Lawrence, S., Ohlin, C. A., Cordes, D. B., Slawin, A. M. Z. & Stasch, A., 9 Oct 2019, In : Chemical Science. Advance Article , 10 p.

    Research output: Contribution to journalArticle

  4. Isothiourea-Catalysed Enantioselective Michael Addition of N-heterocyclic Pronucleophiles to α,β-Unsaturated Aryl Esters

    Smith, A. D. & Liu, H., 14 Oct 2019, (Accepted/In press) In : Chemical Science.

    Research output: Contribution to journalArticle

  5. Turn on of sky-blue thermally activated delayed fluorescence and circularly polarized luminescence (CPL) via increased torsion by a bulky carbazolophane donor

    Sharma, N., Spuling, E., Mattern, C., Li, W., Fuhr, O., Tsuchiya, Y., Adachi, C., Bräse, S., Samuel, I. D. W. & Zysman-Colman, E., 29 May 2019, In : Chemical Science. 10, 27, p. 6689-6696 8 p.

    Research output: Contribution to journalArticle

ID: 245005018

Top