Human serum albumin (HSA) is involved in the transport of metal ions and potential metallodrugs. Depending on the metal, several sites are available, among which are N-terminal (NTS) and multi-metal binding sites (MBS). Despite the large number of X-ray determinations for albumins, only one structure with Zn2+ is available. In this work, the binding to HSA of the VIVO2+ ion was studied by an integrated approach based on spectroscopic and computational methods, which allowed the systems to be characterized even in the absence of X-ray analysis. The behavior depends on the type of albumin, defatted (HSAd) or fatted (HSAf). With HSAd ‘primary’ and ‘secondary’ sites were revealed, NTS with (His3, His9, Asp13, Asp255) and MBS with (His67, His247, Asp249, Asn99 or H2O); with increasing the ratio VIVO2+/HSAd, ‘tertiary’ sites, with one His-N and other donors (Asp/Glu-O or carbonyl-O) are populated. With HSAf, fatty acids (FAs) cause a rotation of the subdomains IA and IIA, which results in the formation of a dinuclear ferromagnetic adduct (VIVO)2D(HSAf) with a μ1,1-Asp249 and the binding of His247, Glu100, Glu252, and His67 or Asn99. FAs hinder also the binding of VIVO2+ to the MBS.
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|Titolo:||Unveiling VIVO2+ Binding Modes to Human Serum Albumins by an Integrated Spectroscopic–Computational Approach|
GARRIBBA, Eugenio (Corresponding)
|Data di pubblicazione:||2020|
|Appare nelle tipologie:||1.1 Articolo in rivista|