De Novo Design of Xeno‐Metallo Coiled Coils

Abstract

Bioinorganic chemists aspire to achieve the same exquisite and highly controlled inorganic chemistry featured in biology. An exciting mimetic approach involves the use of miniature artificial protein scaffolds designed de novo (often based on the coiled coil (CC) scaffold), for reproducing native metal ion sites and their function. Recently, there is increased interest, instead, in the design of xeno-metal sites within CC assemblies. This involves incorporating either non-biological metal ions, cofactors or non-proteinogenic amino acid ligands for metal ion coordination, whilst retaining a minimal CC protein scaffold. Using this approach, one should be able to create functional designs with unique and unusual properties, which combine the advantages of both biology and 'traditional' non-biological inorganic chemistry. It is the recent progress with respect to the design of xeno-metallo CCs which will be discussed in this Focus Review.

Spectroscopic and metal binding properties of a de novo metalloprotein binding a tetrazinc cluster

“…19–22 Meanwhile, lanthanide ion binding sites have been built in the cores of three-helix bundles and have potential as MRI contrast regents. 23 It is noteworthy that uranyl ions can be extracted from seawater by binding to de novo designed binding site in a three-helix bundle. 24 Multinuclear iron-sulfur clusters as well as Cys-rich tetra-cadmium sites have been installed in de novo designed three-helix and four-helix bundles with programmable redox properties.…”

Biocatalysis with Unnatural Amino Acids: Enzymology Meets Xenobiology

“…[170] Clearly,orthogonal translation with various metal-binding ncAAs can lead to new xeno/metallo binding sites. [171] These novel metal-binding sites allow the binding of alternative transition metals or alternative metal cofactors,the reactivity of which is regulated by the protein scaffold. [172] In an ideal case,artificial metalloenzymes should be capable of incorporating at ransition metal obtained from the cellular environment.…”

“…Clearly, orthogonal translation with various metal‐binding ncAAs can lead to new xeno/metallo binding sites . These novel metal‐binding sites allow the binding of alternative transition metals or alternative metal cofactors, the reactivity of which is regulated by the protein scaffold .…”

Biokatalyse mit nicht‐natürlichen Aminosäuren: Enzymologie trifft Xenobiologie

“…Es ist klar zu erkennen, dass die orthogonale Translation mit verschiedenen metallbindenden nkAAs zur Generierung neuartiger Xeno/Metallo‐bindender Zentren führen kann . Diese neuartigen Metallbindungsstellen ermöglichen die Bindung alternativer Übergangsmetalle oder alternativer Metall‐Kofaktoren, deren Reaktivität dabei durch das Proteingrundgerüst reguliert wird .…”