期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 26, 期 49, 页码 11316-11326出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.202001492
关键词
computational chemistry; electron paramagnetic resonance; fatty acids; human serum albumin; metals in medicine
资金
- Regione Autonoma della Sardegna [RASSR79857]
- Universita di Sassari (fondo di Ateneo per la ricerca 2019)
- Spanish MINECO [CTQ2017-87889-P]
- Generalitat de Catalunya [2017SGR1323]
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 Zn(2+)is available. In this work, the binding to HSA of the V(IV)O(2+)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 (HSA(d)) or fatted (HSA(f)). With HSA(d)'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 (VO2+)-O-IV/HSA(d), 'tertiary' sites, with one His-N and other donors (Asp/Glu-O or carbonyl-O) are populated. With HSA(f), fatty acids (FAs) cause a rotation of the subdomains IA and IIA, which results in the formation of a dinuclear ferromagnetic adduct ((VO)-O-IV)(2)(D)(HSA(f)) with a mu(1,1)-Asp249 and the binding of His247, Glu100, Glu252, and His67 or Asn99. FAs hinder also the binding of V(IV)O(2+)to the MBS.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据