کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1317825 | 976589 | 2012 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Full quantum-mechanical structure of the human protein Metallothionein-2 Full quantum-mechanical structure of the human protein Metallothionein-2](/preview/png/1317825.png)
Metallothioneins (MT) are small, metal-binding proteins with diverse functions related to metal ion homeostasis. This paper presents the full 384–388-atom structures of the two native Zn(II)- and the Cd(II)-containing domains of human MT2, optimized with density functional theory. The presented structures are accurate to ~ 0.03 Å for bond lengths and thus provide new physical insight into the detailed electronic structures of MTs, in particular with accurate accounts of bridging vs. terminal bonds not available from NMR or EXAFS. The MT protein enhances the asymmetry, as compared to the protein-free clusters, causing a hierarchy in binding that most likely allows MTs to transfer ions to multiple targets in vivo. The protein polarization is substantial and occurs primarily via the terminal sulfurs, a key mechanism in providing domain-specific electronic structures. The β-domain polarizes its smaller cluster less on average, due to its less polarizable, higher negative charge density, as reflected in longer MS bond lengths and smaller bond orders. This may explain why MT2β is more reactive and dynamic and why MTs have evolved two different-size, asymmetric domains with different metal binding affinities fit for different molecular targets of metal ion transfer.
Full quantum-mechanical structures of the Zn(II) and Cd(II) metallothionein are presented, providing insight into the detailed electronic structures of MTs, bridging vs. terminal bonds, and the through-bond protein polarization of the inorganic clusters via terminal sulfurs. The biological implications are discussed.Figure optionsDownload as PowerPoint slideHighlights
► Quantum mechanical structures of human Cd- and Zn-metallothionein were obtained.
► The MT protein enhances asymmetry of the metal sites.
► This causes a hierarchy in binding, allowing transfer ions to multiple targets.
► Protein polarization occurs via terminal sulfurs and S–HN hydrogen bonds.
► The β-domain, with more negative charge density, binds ions more weakly.
Journal: Journal of Inorganic Biochemistry - Volume 107, Issue 1, February 2012, Pages 15–24