Structural Knowledge for Molecular Optimization: The Cases of Metal‐Mediated Protein–Protein Interactions and Structural Vaccinology

Abstract

The knowledge of the structural properties of molecules and of their recognition and interaction patterns with partners is a key feature for understanding their functional properties. This is particularly true for the comprehension of complex cellular processes in which several interacting proteins are involved. The structural characterization of all the molecules involved in a process allows the understanding of the malfunctioning of such process and eventually the design of biomole-[a] Magnetic Lucia Banci is a Professor of Chemistry at the University of Florence. She has extensive expertise and has provided original contributions and breakthroughs in Structural Biology and in biological NMR spectroscopy. She has addressed and unraveled many aspects of the biology of metal ions in biological systems. The innovative in cell NMR approach developed by Lucia Banci and her group allows for the detection of human individual proteins in living human cells with atomic level resolution. She also exploited the extensive knowledge of structural biology approaches through NMR expertise to develop an absolutely innovative approach to vaccine design, based on the knowledge of the structure of the pathogen antigens and of the interaction patterns with antibodies, to design structure-based vaccines. Francesca Cantini graduated in Chemistry in 2000 and received her PhD in Structural Biology in 2004 at the University of Florence. She is now a permanent research scientist at the University of Florence. Her research is focused on the structural and dynamic characterization of proteins and protein complexes through NMR spectroscopy. Since 2000, her research activity is dedicated to the comprehension of the molecular mechanisms responsible for metal trafficking and metallo-protein maturation. Since 2005, she collaborates with GSK Vaccines (Siena, Italy) on the structural characterization of vaccine candidates and their interaction with antibodies. Eur. J. Inorg. Chem. 2018, 4108-4116 4109mining protein recognition and interaction. Knowledge of such factors permits the description of cellular processes in a systemwide frame, as well as the understanding of the malfunctioning of such processes and the design of biomolecules to counterbalance it.

Galvanization of Protein–Protein Interactions in a Dynamic Zinc Interactome

“…It is also modulated when Zn 2+ donors interact directly with other residues and the main chain or acid-base properties of active groups are affected by the local environment. Additionally, an interaction surface built by burying noncovalent interactions is the important selectivity factor of interacting partners in metal-mediated PPI [97]. Another important factor contributing to the structure and stability of the complex is metal-coupled folding.…”