title: Artificial Diiron Enzymes with a De Novo Designed Four-Helix Bundle Structure.
abstract: A single polypeptide chain may provide an astronomical number of conformers. Nature selected only a trivial number of them through evolution, composing an alphabet of scaffolds, that can afford the complete set of chemical reactions needed to support life. These structural templates are so stable that they allow several mutations without disruption of the global folding, even having the ability to bind several exogenous cofactors. With this perspective, metal cofactors play a crucial role in the regulation and catalysis of several processes. Nature is able to modulate the chemistry of metals, adopting only a few ligands and slightly different geometries. Several scaffolds and metal-binding motifs are representing the focus of intense interest in the literature. This review discusses the widespread four-helix bundle fold, adopted as a scaffold for metal binding sites in the context of de novo protein design to obtain basic biochemical components for biosensing or catalysis. In particular, we describe the rational refinement of structure/function in diiron-oxo protein models from thedue ferri(DF) family. The DF proteins were developed by us through an iterative process of design and rigorous characterization, which has allowed a shift from structural to functional models. The examples reported herein demonstrate the importance of the synergic application of de novo design methods as well as spectroscopic and structural characterization to optimize the catalytic performance of artificial enzymes.
authors.affiliation: Department of Chemical Sciences, University of Naples "Federico II", Via Cintia, 80126 Naples, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Chino
authors.affiliation: Department of Chemical Sciences, University of Naples "Federico II", Via Cintia, 80126 Naples, Italy; IBB, CNR, Via Mezzocannone 16, 80134 Naples, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Maglio
authors.affiliation: Department of Chemical Sciences, University of Naples "Federico II", Via Cintia, 80126 Naples, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Nastri
authors.affiliation: Department of Structural and Functional Biology, University of Naples "Federico II", Via Cintia, 80126 Naples, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pavone
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco San Francisco, CA 94158, USA.
authors.forename: William F
authors.initials: WF
authors.lastname: DeGrado
authors.affiliation: Department of Chemical Sciences, University of Naples "Federico II", Via Cintia, 80126 Naples, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Lombardi
keywords: DF models; Enzyme mimics; Helical structures; Iron; Metalloenzymes; Protein design