The thermodynamics of protein interactions with essential first row transition metals

• Metal ions are essential for all living organisms and participate in a wide variety of cellular processe
• Metal ion bioavailability and coordination chemistry could dictate the selectivity and affinity of metal ions to proteins
• The thermodynamics of metals ions binding to biological molecules can be quantified by ITC
• ITC is a unique technique able to quantify the enthalpic and entropic contributions of the binding interaction
• Carefully designed ITC experiments and proper controls are necessary for the accurate determination of all thermodynamic parameters

BackgroundThe 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 reviewA 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 row transition metals with relevant proteins and highlight major findings from these thermodynamic studies.General significanceThe thermodynamic characterization of metal ion–protein 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 conclusionsIsothermal 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. This article is part of a Special Issue entitled Microcalorimetry in the BioSciences — Principles and Applications, edited by Fadi Bou-Abdallah.

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