5byq

Publication Abstract from PubMed

[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[mu-(SCH2)2X](CN)2(CO)4(2-) 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 A and the active semisynthetic enzyme, CpI(ADT), at 1.63 A. 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 CpI(ADT). Additionally we present the high resolution crystal structures of the semisynthetic bacterial [FeFe]-hydrogenases CpI(PDT) (X = CH2), CpI(ODT) (X = O) and CpI(SDT) (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 CpI(ADT). 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.

A structural view of synthetic cofactor integration into [FeFe]-hydrogenases.,Esselborn J, Muraki N, Klein K, Engelbrecht V, Metzler-Nolte N, Apfel UP, Hofmann E, Kurisu G, Happe T Chem Sci. 2016 Feb 1;7(2):959-968. doi: 10.1039/c5sc03397g. Epub 2015 Oct 26. PMID:29896366^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.