The thermodynamics of protein interactions with essential first row transition metals

Abstract

Background The binding of metal ions to proteins is a crucial process required for their catalytic activity, structural stability and/or functional regulation. Isothermal titration calorimetry provides a wealth of fundamental information which when combined with structural data allow for a much deeper understanding of the underlying molecular mechanism. Scope of review A rigorous understanding of any molecular interaction requires in part an in-depth quantification of its thermodynamic properties. Here, we provide an overview of recent studies that have used ITC to quantify the interaction of essential first raw transition metals with relevant proteins and highlight major findings from these thermodynamic studies. General significance The thermodynamic characterization of metal ions-proteins interactions is one important step to understanding the role that metal ions play in living systems. Such characterization has important implications not only to elucidating proteins’ structure-function relationships and biological properties but also in the biotechnology sector, medicine and drug design particularly since a number of metal ions are involved in several neurodegenerative diseases. Major conclusions Isothermal titration calorimetry measurements can provide complete thermodynamic profiles of any molecular interaction through the simultaneous determination of the reaction binding stoichiometry, binding affinity as well as the enthalpic and entropic contributions to the free energy change thus enabling a more in-depth understanding of the nature of these interactions.

Heterogeneous-Backbone Foldamer Mimics of Zinc Finger Tertiary Structure

“…The unnatural turn replacements employed in 2 and 3 are proven substitutions for canonical type-I and type-II turns; 30 however, they tend to promote mirror image type-I’ and II’ turn conformations that may be incompatible with the overlapping type-VIII turn directly following in Sp1–3 . Finally, the side chain of Glu 6 is lost in the two analogues. This residue is found near the zinc ion in the NMR structure, 25 where it may contribute as a second sphere ligand and/or stabilize the metal binding site through interaction with His 24 .…”

“…We reasoned the enhanced flexibility of δ X relative to δ O might allow the two flanking Cys residues to adopt an appropriate metal binding geometry. Peptides 7 and 8 restore the native Glu 6 side chain to 2 and 3 , respectively, and were designed to test the hypothesis that the loss of this side chain accompanying backbone modification was responsible for the inability to fold.…”

“…It has been estimated that a third of all proteins bind to some metal ion and half of enzymes require a specific metal to function. 6 Despite this ubiquity in nature, examples of metal binding in foldamers represent only a small fraction of the many unnatural folded units reported to date. 7 Most examples have been based on oligomers with metal-coordinating backbones, 8 while some have shown metal binding is possible in designed oligomers with peptide-based backbones closer to those found in nature.…”

A rationally designed peptoid for the selective chelation of Zn2+ over Cu2+

“…Initially, two mixture solutions were prepared, in which the ratio between Zn 2+ and Cu 2+ was varied between 1 : 2 and 1 : 3, while keeping the other metal ions in excess owing to their abundance in the human body with respect to Zn 2+ . 26 Both PT-1 and the two mixtures (A with the Zn 2+ : Cu 2+ : Fe 3+ : Ca 2+ : Mg 2+ : Na + : K + ratio 1 : 2 : 5 : 10 : 10 : 10 : 10 and B with the ratio 1 : 3 : 5 : 10 : 10 : 10 : 10) were prepared in the SBF. Each mixture was added to PT-1 in two different UV-Vis experiments and the spectra were recorded.…”

Growing Popularity of Ultrasensitive Microcalorimetry

“…Calorimetry has also found its use in the investigation of the fate of food products in the gastrointestinal tract [30]. Interaction of proteins with essential 1st row transition metals has also recently been reported [31,32]. Isothermal titration calorimetry and differential scanning calorimetry have also found role in getting insights into inhibition of aggregation or fibrillation of proteins, which is essential in prevention of neurodegenerative diseases [33,34].…”