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dc.contributor.authorWu, Dongmei
dc.contributor.authorGucwa, Michal
dc.contributor.authorCzub, Mateusz P.
dc.contributor.authorCooper, David R.
dc.contributor.authorShabalin, Ivan G.
dc.contributor.authorFritzen, Remi
dc.contributor.authorArya, Swati
dc.contributor.authorSchwarz-Linek, Ulrich
dc.contributor.authorBlindauer, Claudia A.
dc.contributor.authorMinor, Wladek
dc.contributor.authorStewart, Alan J.
dc.identifier.citationWu , 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 2023 , ' Structural and biochemical characterisation of Co 2+ -binding sites on serum albumins and their interplay with fatty acids ' , Chemical Science , vol. 14 , no. 23 , pp. 6244-6258 .
dc.identifier.otherORCID: /0000-0001-7978-9507/work/135850748
dc.identifier.otherORCID: /0000-0003-4580-1840/work/135851261
dc.identifier.otherORCID: /0000-0003-0526-223X/work/135851271
dc.identifier.otherORCID: /0000-0003-3457-8364/work/135851476
dc.descriptionFunding: The authors gratefully acknowledge the China Scholarship Council for funding a PhD scholarship for D. W. This work was also funded by the Leverhulme Trust (grant no. RPG-2017-214). I. G. S., W. M. and M. G. were funded by NIH grant R01-GM132595 and Harrison Family Funds. M. P. C. acknowledges the support of a Robert R. Wagner Fellowship at the University of Virginia. R. F. was supported by the Biological and Biotechnological Sciences Research Council (grant no. BB/V014684/1).en
dc.description.abstractSerum albumin–Co2+ interactions are of clinical importance. They play a role in mediating the physiological effects associated with cobalt toxicity and are central to the albumin cobalt binding (ACB) assay for diagnosis of myocardial ischemia. To further understand these processes, a deeper understanding of albumin–Co2+ interactions is required. Here, we present the first crystallographic structures of human serum albumin (HSA; three structures) and equine serum albumin (ESA; one structure) in complex with Co2+. Amongst a total of sixteen sites bearing a cobalt ion across the structures, two locations were prominent, and they relate to metal-binding sites A and B. Site-directed mutagenesis and isothermal titration calorimetry (ITC) were employed to characterise sites on HSA. The results indicate that His9 and His67 contribute to the primary (putatively corresponding to site B) and secondary Co2+-binding sites (site A), respectively. The presence of additional multiple weak-affinity Co2+ binding sites on HSA was also supported by ITC studies. Furthermore, addition of 5 molar equivalents of the non-esterified fatty acid palmitate (C16:0) reduced the Co2+-binding affinity at both sites A and B. The presence of bound myristate (C14:0) in the HSA crystal structures provided insight into the fatty acid-mediated structural changes that diminish the affinity of the protein toward Co2+. Together, these data provide further support for the idea that ischemia-modified albumin corresponds to albumin with excessive fatty-acid loading. Collectively, our findings provide a comprehensive understanding of the molecular underpinnings governing Co2+ binding to serum albumin.
dc.relation.ispartofChemical Scienceen
dc.subjectQD Chemistryen
dc.subjectQH301 Biologyen
dc.titleStructural and biochemical characterisation of Co2+-binding sites on serum albumins and their interplay with fatty acidsen
dc.typeJournal articleen
dc.contributor.sponsorThe Leverhulme Trusten
dc.contributor.institutionUniversity of St Andrews. Cellular Medicine Divisionen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. University of St Andrewsen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Sir James Mackenzie Institute for Early Diagnosisen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.description.statusPeer revieweden

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