DNA Cleavage by a De Novo Designed Protein–Titanium Complex

Titanium is one of the most abundant elements on Earth but is commonly thought to have no role in biology because of its propensity to hydrolyze. Nature stabilizes hard Lewis acidic metals from hydrolysis using a variety of mechanisms, providing inspiration for how titanium can be stabilized using b...

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Bibliographic Details
Published in:Inorganic chemistry 2020-08, Vol.59 (16), p.11248-11252
Main Authors: Paredes, Alexander, Loh, Brittany M, Peduzzi, Olivia M, Reig, Amanda J, Buettner, Katherine M
Format: Article
Language:English
Subjects:
Catalytic Domain
DNA - chemistry
Hydrolysis
Metalloproteins - chemistry
Proof of Concept Study
Titanium - chemistry
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Summary:Titanium is one of the most abundant elements on Earth but is commonly thought to have no role in biology because of its propensity to hydrolyze. Nature stabilizes hard Lewis acidic metals from hydrolysis using a variety of mechanisms, providing inspiration for how titanium can be stabilized using biological ligands. The well-characterized Due Ferri single-chain (DFsc) de novo designed protein was developed to bind and stabilize iron and provides a binding site with hard Lewis basic residues able to bind two metal ions. We demonstrate that the DFsc scaffold stably binds 2 equiv of titanium and protects them from unwanted hydrolysis. The Ti4+–DFsc protein complex was tested for its ability to hydrolytically cleave DNA, where it was seen to linearize plasmid DNA in an overnight reaction. Ti4+–DFsc is thus the first example of a functional, soluble titanium–protein complex.
ISSN:0020-1669
1520-510X
DOI:10.1021/acs.inorgchem.0c01707