The thermodynamics of protein interactions with essential first row transition metals

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 row transition metals with relevant proteins and highlight major findings from these thermodynamic studies. General significance The 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 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. This article is part of a Special Issue entitled Microcalorimetry in the BioSciences - Principles and Applications, edited by Fadi Bou-Abdallah.