4 publications

4 publications

A Structural View of Synthetic Cofactor Integration into [FeFe]-Hydrogenases

Apfel, U.-P.; Happe, T.; Kurisu, G.

Chem. Sci. 2016, 7, 959-968, 10.1039/C5SC03397G

Crystal structures of semisynthetic [FeFe]-hydrogenases with variations in the [2Fe] cluster show little structural differences despite strong effects on activity.


Metal: Fe
Ligand type: CN; CO; Dithiolate
Anchoring strategy: Dative
Optimization: Chemical
Reaction: H2 evolution
Max TON: ---
ee: ---
PDB: 4XDC
Notes: H2 evolution activity of the ArM: 2874 (mmol H2)*min-1*(mg protein)-1.

Chalcogenide Substitution in the [2Fe] Cluster of [FeFe]-Hydrogenases Conserves High Enzymatic Activity

Apfel, U.-P.; Happe, T.

Dalton Trans. 2017, 46, 16947-16958, 10.1039/C7DT03785F

Combination of biological and chemical methods allow for creation of [FeFe]-hydrogenases with an artificial synthetic cofactor.


Metal: Fe
Ligand type: CN; CO; Diselenolate
Anchoring strategy: Dative
Optimization: Chemical
Reaction: H2 evolution
Max TON: ---
ee: ---
PDB: 5OEF
Notes: ---

Spontaneous Activation of [FeFe]-Hydrogenases by an Inorganic [2Fe] Active Site Mimic

Happe, T.

Nat. Chem. Biol. 2013, 9, 607-609, 10.1038/Nchembio.1311

Hydrogenases catalyze the formation of hydrogen. The cofactor ('H-cluster') of [FeFe]-hydrogenases consists of a [4Fe-4S] cluster bridged to a unique [2Fe] subcluster whose biosynthesis in vivo requires hydrogenase-specific maturases. Here we show that a chemical mimic of the [2Fe] subcluster can reconstitute apo-hydrogenase to full activity, independent of helper proteins. The assembled H-cluster is virtually indistinguishable from the native cofactor. This procedure will be a powerful tool for developing new artificial H2-producing catalysts.


Metal: Fe
Ligand type: CN; CO; Dithiolate
Anchoring strategy: Dative
Optimization: Chemical
Reaction: H2 evolution
Max TON: ---
ee: ---
PDB: ---
Notes: ---

The Plasticity of Redox Cofactors: From Metalloenzymes to Redox-Active DNA

Review

Happe, T.; Hemschemeier, A.

Nat. Rev. Chem. 2018, 2, 231-243, 10.1038/s41570-018-0029-3

Metal cofactors considerably widen the catalytic space of naturally occurring enzymes whose specific and enantioselective catalytic activity constitutes a blueprint for economically relevant chemical syntheses. To optimize natural enzymes and uncover novel reactivity, we need a detailed understanding of cofactor–protein interactions, which can be challenging to obtain in the case of enzymes with sophisticated cofactors. As a case study, we summarize recent research on the [FeFe]-hydrogenases, which interconvert protons, electrons and dihydrogen at a unique iron-based active site. We can now chemically synthesize the complex cofactor and incorporate it into an apo-protein to afford functional enzymes. By varying both the cofactor and the polypeptide components, we have obtained detailed knowledge on what is required for a metal cluster to process H2. In parallel, the design of artificial proteins and catalytically active nucleic acids are advancing rapidly. In this Perspective, we introduce these fields and outline how chemists and biologists can use this knowledge to develop novel tailored semisynthetic catalysts.


Notes: ---