A structural view of synthetic cofactor integration into [FeFe]-hydrogenases

J. Esselborn, N. Muraki, K. Klein, V. Engelbrecht, N. Metzler-Nolte, U. P. Apfel, E. Hofmann, G. Kurisu, T. Happe

Research output: Contribution to journalArticlepeer-review

94 Citations (Scopus)

Abstract

[FeFe]-hydrogenases are nature's fastest catalysts for the evolution or oxidation of hydrogen. Numerous synthetic model complexes for the [2Fe] subcluster (2FeH) of their active site are known, but so far none of these could compete with the enzymes. The complex Fe2[μ-(SCH2)2X](CN)2(CO)42- with X = NH was shown to integrate into the apo-form of [FeFe]-hydrogenases to yield a fully active enzyme. Here we report the first crystal structures of the apo-form of the bacterial [FeFe]-hydrogenase CpI from Clostridium pasteurianum at 1.60 Å and the active semisynthetic enzyme, CpIADT, at 1.63 Å. The structures illustrate the significant changes in ligand coordination upon integration and activation of the [2Fe] complex. These changes are induced by a rigid 2FeH cavity as revealed by the structure of apoCpI, which is remarkably similar to CpIADT. Additionally we present the high resolution crystal structures of the semisynthetic bacterial [FeFe]-hydrogenases CpIPDT (X = CH2), CpIODT (X = O) and CpISDT (X = S) with changes in the headgroup of the dithiolate bridge in the 2FeH cofactor. The structures of these inactive enzymes demonstrate that the 2FeH-subcluster and its protein environment remain largely unchanged when compared to the active enzyme CpIADT. As the active site shows an open coordination site in all structures, the absence of catalytic activity is probably not caused by steric obstruction. This demonstrates that the chemical properties of the dithiolate bridge are essential for enzyme activity.

Original languageEnglish
Pages (from-to)959-968
Number of pages10
JournalChemical Science
Volume7
Issue number2
DOIs
Publication statusPublished - 2016
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)

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