7MBL

Crystal structure of Equine Serum Albumin in complex with Cobalt (II)

Summary for 7MBL

• Entry DOI: 10.2210/pdb7mbl/pdb
• Descriptor: Serum albumin, COBALT (II) ION, SULFATE ION, ... (4 entities in total)
• Functional Keywords: serum albumin, complex with cobalt, transport protein, structural genomics, center for structural genomics of infectious diseases, csgid
• Biological source: Equus caballus (Horse)
• Total number of polymer chains: 1
• Total formula weight: 66447.00

Authors

Shabalin, I.G.,Czub, M.P.,Handing, K.B.,Cymborowski, M.T.,Grabowski, M.,Cooper, D.R.,Minor, W.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2021-03-31, release date: 2021-04-14, Last modification date: 2024-10-09)

Primary citation

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.
Structural and biochemical characterisation of Co 2+ -binding sites on serum albumins and their interplay with fatty acids.
Chem Sci, 14:6244-6258, 2023

PubMed Abstract: Serum albumin-Co 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-Co 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 Co. 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 Co-binding sites (site A), respectively. The presence of additional multiple weak-affinity Co 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 Co-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 Co. 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 Co binding to serum albumin.

PubMed: 37325156
DOI: 10.1039/d3sc01723k

Experimental method

X-RAY DIFFRACTION (2.7 Å)