8EY5

Human Serum Albumin with Cobalt (II) and Myristic Acid - crystal 3

8EY5 の概要

• エントリーDOI: 10.2210/pdb8ey5/pdb
• 関連するPDBエントリー: 7MBL 8EW4 8EW7
• 分子名称: Serum albumin, COBALT (II) ION, MYRISTIC ACID, ... (4 entities in total)
• 機能のキーワード: serum albumin, complex with cobalt, transport protein, albumin with fatty acid, structural genomics, psi-biology, center for structural genomics of infectious diseases, csgid, center for structural biology of infectious diseases, csbid
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 68921.22

構造登録者

Gucwa, M.,Cooper, D.R.,Stewart, A.J.,Minor, W.,Center for Structural Genomics of Infectious Diseases (CSGID),Center for Structural Biology of Infectious Diseases (CSBID) (登録日: 2022-10-26, 公開日: 2022-11-09, 最終更新日: 2024-10-16)

主引用文献

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 Co2+-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

実験手法

X-RAY DIFFRACTION (3.1 Å)