Title
Truncated domains of human serum albumin improves the binding efficiency of uremic toxins: A surface plasmon resonance and computational approach
Author
Aparna Nerusu, Papa Rao Vaikuntapu, Dinesh Kumar Chinthapalli, Appa Rao Podile, Rajagopal Subramanyam
Year
2019
Journal
International Journal of Biological Macromolecules
Abstract
Albumin binding is the major cause for the toxicity of protein bound uremic toxins (PBUTs) in uremic patients. Albumin binding property is exploited to address this issue, as some of the extracorporeal dialysis systems use albumin as dialysate. In this line, a detailed study about binding of PBUTs to human serum albumin (HSA) and its domains gives valuable information. The focus of this work emphasizes the mechanism of binding of HSA and its domains with a few selected PBUTs such as hippuric acid (HA), indole acetic acid (IAA) and melatonin. The HSA domains (D2, D3 and D2–3) were expressed in Pichia pastoris and purified by using Albupure matrix. The binding of the expressed domains and HSA, with PBUTs, was measured using surface plasmon resonance and analyzed. All the three domains have significant affinity towards PBUTs, while D3 had greater affinity for all the three selected PBUTs. Docking studies showed that the basic amino acid, lysine, was forming hydrogen bond with PUBTs inorder to stabile these complex. This study would be having therapeutic importance for preparing the extracorporeal dialysis systems, in combination of different domains of HSA to remove the PBUTs.
Instrument
J-1500
Keywords
Circular dichroism, Secondary structure, Thermal stability, Tertiary structure, Biochemistry