Unveiling VIVO2+ Binding Modes to Human Serum Albumins by an Integrated Spectroscopic-Computational Approach
Sciortino, Giuseppe (Universitat Autònoma de Barcelona. Departament de Química)
Sanna, Daniele (Consiglio Nazionale delle Ricerche. Istituto di Chimica Biomolecolare)
Lubinu, Giuseppe (Università di Sassari. Dipartimento di Chimica e Farmacia)
Maréchal, Jean-Didier (Universitat Autònoma de Barcelona. Departament de Química)
Garribba, Eugenio (Università di Sassari. Dipartimento di Chimica e Farmacia)

Data:	2020
Resum:	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.
Ajuts:	Agencia Estatal de Investigación CTQ2017-87889-P Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1323
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Llengua:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Matèria:	Computational chemistry ; Electron paramagnetic resonance ; Fatty acids ; Human serum albumin ; Metals in medicine ; SDG 3 - Good Health and Well-being
Publicat a:	Chemistry (Weinheim), Vol. 26, Issue 49 (September 2020) , p. 11316-11326, ISSN 1521-3765

DOI: 10.1002/chem.202001492
PMID: 32436606

Postprint 15 p, 1.2 MB

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