Alan Stewart Group – Metal ions in Medicine
Group Highlights
Our work is centred on how metal ions, such as Zn2+, Ca2+ and Co2+ are transported through the blood and how their mishandling can lead to disease. A key part of my group’s activity is the study of their interactions with circulatory proteins. At a cell and systems level, we are interested in how these interactions have a functional impact. We commonly utilise methods that examine the movement of Zn2+ and Ca2+ ions within cells and across membranes or measure their direct physiological functional outputs (e.g. coagulatory processes). Over the last few years, we have also worked closely with colleagues across the North Haugh particularly, the Mass Spectrometry Facility in St Andrews in the utilisation of quantitative proteomics clinical studies.
Please visit our group website: https://metalion.wp.st-andrews.ac.uk/
Effects of fatty acid binding at the FA2 site on the primary zinc site of human serum albumin. (A) Structure of HSA with 5 molecules of myristate bound (PDB: 1BJ5). (B) Overlay of the main zinc-binding site in the myristate-bound structure (in green; PDB: 1BJ5) and the zinc-bound structure (in blue; PDB: 5IJF). A structural change is induced by fatty acid binding. This triggers the zinc-coordinating residue His67 to move 8 Å away from the other two coordinating side chains. Figure taken from Sobczak et al. (2021) Chem. Sci. 12: 4079-4093.
Research
Bilateral BBSRC-FAPESP: A “speciomic” toolkit to investigate fatty acid-mediated changes in plasma zinc speciation and their physiological effects.
Tenovus Scotland: Assessment of the predictive value of plasma proteins in oesophageal adenocarcinoma treatment
British Heart Foundation: Plasma non-esterified fatty acids and fibrin clot formation in obesity – a relationship forged in zinc?
British Heart Foundation: Role of plasma fatty acid and zinc dynamics in platelet functioning: Implications for pathological clotting
Group Members
Dr Remi Fritzen; Research Fellow
Dongmei Wu; PhD student
Jordan Marsh; PhD student
Stephen Hierons; PhD student
Hasnain Ahmed; PhD student
Amy Davies; Visiting Scholar
Publications
Chapters
Exploring ICP-MS as a versatile technique: from imaging to chemical speciation analysis
Amais, R. S., de Andrade, A. M., Santos da Silva, A. B., Freitas, D. C., Francischini, D. D. S., Stewart, A. J. & Arruda, M. A. Z., 24 May 2022, ICP-MS and trace element analysis as tools for better understanding medical conditions. Arruda, M. A. Z. & de Jesus, J. R. (eds.). Amsterdam: Elsevier, p. 141-177 37 p. (Comprehensive analytical chemistry; vol. 97).
Research output: Chapter in Book/Report/Conference proceeding › Chapter
The formation and Zn2+-dependence of histidine-rich glycoprotein-containing immune complexes.
Kassaar, O., Powis, S. J. & Stewart, A. J., Dec 2012, Advances in Medicine and Biology. Berhardt, L. V. (ed.). Nova Science Publishers, Vol. 58. p. 153-166 14 p.
Research output: Chapter in Book/Report/Conference proceeding › Chapter
Articles
Changes in fibrin clot properties in patients after Roux en-Y gastric bypass surgery
Abbas, K., Hierons, S. J., Pechlivani, N., Phoenix, F., Alexander, R., King, R., Ajjan, R. A. & Stewart, A. J., 29 Feb 2024, (E-pub ahead of print) In: Research and Practice in Thrombosis and Haemostasis. 8, 2, 8 p., e102361.
Research output: Contribution to journal › Article › peer-review
Recent advances in metalloproteomics
Coverdale, J. P. C., Polepalli, S., Arruda, M. A. Z., Santos Da Silva, A. B., Stewart, A. J. & Blindauer, C. A., 13 Jan 2024, In: Biomolecules. 14, 1, 31 p., 104.
Research output: Contribution to journal › Review article › peer-review
Five new diarylbutyrolactones and sesquilignans from Saussurea medusa and their inhibitory effects on LPS-induced NO production
Cao, J-Y., Wang, Z-Y., Stewart, A. J., Dong, Q., Zhao, Y., Mei, L-J., Tao, Y-D. & Yu, R-T., 1 Jun 2023, In: Planta Medica. 89, 06, p. 663-673 11 p.
Research output: Contribution to journal › Article › peer-review
Investigating native metal ion binding sites in mammalian histidine-rich glycoprotein
Ackermann, K., Khazaipoul, S., Wort, J., Sobczak, A. I. S., El Mkami, H., Stewart, A. J. & Bode, B. E., 12 Apr 2023, In: Journal of the American Chemical Society. 145, 14, p. 8064-8072 9 p.
Research output: Contribution to journal › Article › peer-review
Magnesium deficiency and cardiometabolic disease
Fritzen, R., Davies, A., Veenhuizen, M., Campbell, M., Pitt, S. J., Ajjan, R. A. & Stewart, A. J., 17 May 2023, In: Nutrients. 15, 10, 19 p., 2355.
Research output: Contribution to journal › Article › peer-review
Optimised plasma sample preparation and LC-MS analysis to support large-scale proteomic analysis of clinical trial specimens: application to the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial
O'Rourke, M. B., Januszewski, A. S., Sullivan, D. R., Lengyel, I., Stewart, A. J., Arya, S., Ma, R., Galande, S., Hardikar, A. A., Joglekar, M. V., Keech, A. C., Jenkins, A. J. & Molloy, M. P., 16 May 2023, In: Proteomics - Clinical Applications. 17, 3, 10 p., 2200106.
Research output: Contribution to journal › Article › peer-review
Structural and biochemical characterisation of Co2+-binding sites on serum albumins and their interplay with fatty acids
Wu, D., Gucwa, M., Czub, M. P., Cooper, D. R., Shabalin, I. G., Fritzen, R., Arya, S., Schwarz-Linek, U., Blindauer, C. A., Minor, W. & Stewart, A. J., 21 Jun 2023, In: Chemical Science. 14, 23, p. 6244-6258 15 p.
Research output: Contribution to journal › Article › peer-review
The role of Zn2+ in shaping intracellular Ca2+ dynamics in the heart
Dorward, A. M., Stewart, A. J. & Pitt, S. J., 16 Jun 2023, In: Journal of General Physiology. 155, 7, 18 p., e202213206.
Research output: Contribution to journal › Article › peer-review
Total plasma magnesium, zinc, copper and selenium concentrations in obese patients before and after bariatric surgery
Hierons, S. J., Catchpole, A., Abbas, K., Wong, W., Giles, M. S., Miller, G. V., Ajjan, R. A. & Stewart, A. J., 1 Apr 2023, In: BioMetals. 36, 2, p. 241-253 13 p.
Research output: Contribution to journal › Article › peer-review
Zn2+ differentially influences the neutralisation of heparins by HRG, fibrinogen, and fibronectin.
Sobczak, A. I. S., Ajjan, R. A. & Stewart, A. J., 23 Nov 2023, In: International Journal of Molecular Sciences. 24, 23, 11 p., 16667.
Research output: Contribution to journal › Article › peer-review
Other publications
Editorial: Insulin resistance and cardiovascular disease
Stewart, A. J., Tuncay, E., Pitt, S. J. & Rainbow, R. D., 4 Aug 2023, In: Frontiers in Endocrinology. 14, 3 p., 1266173.
Research output: Contribution to journal › Editorial › peer-review
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 journal › Letter › peer-review
The reduced Co2+-binding ability of ischaemia-modified albumin is unlikely to be because of oxidative modification of the N-terminus
Stewart, A. J. & Blindauer, C. A., Dec 2015, In: Liver International. 35, 12, p. 2622-2623 2 p.
Research output: Contribution to journal › Letter › peer-review
Albumin research in the 21st century
Peters Jr, T. & Stewart, A. J., Dec 2013, In: Biochimica et Biophysica Acta - General Subjects. 1830, 12, p. 5351-5353 3 p.
Research output: Contribution to journal › Editorial
Design of mutated forms of human serum albumin with altered metal binding characteristics for pharmacological or cell culture uses.
Berezenko, S., Sadler, P. J., Stewart, A. J., Blindauer, C. A. & Bunyan, K. E., 5 Feb 2004, IPC No. C07K 14/765 (2006.01), Patent No. WO/2004/011499
Research output: Patent
Contact
Dr Alan J. Stewart PhD FRSB FRSC
Reader in Molecular Medicine
School of Medicine
Medical and Biological Sciences Building
University of St Andrews
St Andrews
Fife, KY16 9TF
United Kingdom
E-mail: [email protected]
Tel: +44 (0)1334 463546
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