PhD student, Dongmei Wu (from the Stewart group) has had a joint first author paper focussed on serum albumin interaction with Co2+ , accepted for publication in the RSC journal, Chemical Science. The work was a collaboration between several groups, including that of Prof. Wladek Minor from the Univeristy of Virginia (who is joint lead author with Dr Stewart) and Prof. Claudia Blindauer from the University of Warwick.
Serum 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 was required. In the paper, the first crystallographic structures of human serum albumin (HSA; three structures) and equine serum albumin (ESA; one structure) in complex with Co2+ are presented. 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 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.