2 publications

2 publications

Redox-Switchable Siderophore Anchor Enables Reversible Artificial Metalloenzyme Assembly

Duhme-Klair, A.K.; Wilson, K.S.

Nat. Catal. 2018, 1, 680-688, 10.1038/s41929-018-0124-3

Artificial metalloenzymes that contain protein-anchored synthetic catalysts are attracting increasing interest. An exciting, but still unrealized advantage of non-covalent anchoring is its potential for reversibility and thus component recycling. Here we present a siderophore–protein combination that enables strong but redox-reversible catalyst anchoring, as exemplified by an artificial transfer hydrogenase (ATHase). By linking the iron(iii)-binding siderophore azotochelin to an iridium-containing imine-reduction catalyst that produces racemic product in the absence of the protein CeuE, but a reproducible enantiomeric excess if protein bound, the assembly and reductively triggered disassembly of the ATHase was achieved. The crystal structure of the ATHase identified the residues involved in high-affinity binding and enantioselectivity. While in the presence of iron(iii), the azotochelin-based anchor binds CeuE with high affinity, and the reduction of the coordinated iron(iii) to iron(ii) triggers its dissociation from the protein. Thus, the assembly of the artificial enzyme can be controlled via the iron oxidation state.

Metal: Ir
Ligand type: Cp*; Pyridine sulfonamide
Host protein: CeuE
Anchoring strategy: Supramolecular
Optimization: Chemical & genetic
Max TON: ---
ee: 35.4
Notes: Redox switchable iron(III)-azotochelin anchor

Supramolecular Interactions Between Functional Metal Complexes and Proteins


Duhme-Klair, A.K.

Dalton Trans. 2009, 10141, 10.1039/b915776j

This perspective illustrates the principles and applications of molecular recognition directed binding of transition metal complexes to proteins. After a brief introduction into non-covalent interactions and the importance of complementarity, the focus of the first part is on biological systems that rely on non-covalent forces for metal complex binding, such as proteins involved in bacterial iron uptake and the oxygen-storage protein myoglobin. The second part of the perspective will illustrate how the replacement of native with non-native metal-centres can give rise to artificial metalloenzymes with novel catalytic properties. Subsequently, examples of spectroscopic probes that exploit the characteristic photophysical properties of metal-complexes for the non-covalent labelling, visualisation and investigation of proteins will be described. Finally, the use of kinetically inert metal complexes as scaffolds in drug design will be discussed and it will be highlighted how the binding of metal ions or organometallic fragments to existing drugs or drug candidates can improve their activity or even alter their mode of action.

Notes: ---