Dithiomethylether as a Ligand in the Hydrogenase H-Cluster

Abstract

An X-ray crystallographic refinement of the H-cluster of [FeFe]-hydrogenase from Clostridium pasteurianum has been carried out to close-to atomic resolution and is the highest resolution [FeFe]-hydrogenase presented to date. The 1.39 A, anisotropically refined [FeFe]-hydrogenase structure provides a basis for examining the outstanding issue of the composition of the unique nonprotein dithiolate ligand of the H-cluster. In addition to influencing the electronic structure of the H-cluster, the composition of the ligand has mechanistic implications due to the potential of the bridge-head gamma-group participating in proton transfer during catalysis. In this work, sequential density functional theory optimizations of the dithiolate ligand embedded in a 3.5-3.9 A protein environment provide an unbiased approach to examining the most likely composition of the ligand. Structural, conformational, and energetic considerations indicate a preference for dithiomethylether as an H-cluster ligand and strongly disfavor the dithiomethylammonium as a catalytic base for hydrogen production.

Spin distribution of the H-cluster in the Hox–CO state of the [FeFe] hydrogenase from Desulfovibrio desulfuricans: HYSCORE and ENDOR study of 14N and 13C nuclear interactions

“…The distal iron (relative to the [4Fe-4S] H subcluster) has an open coordination site, which is believed to be the site for hydrogen binding [6,21,22]. Despite extensive investigations of the structure of the H-cluster by various methods, the identity of the central atom in the dithiol bridging ligand has not been resolved yet, so far CH 2 , NH, and O were proposed [17,20,23,24]. On the basis of mechanistic considerations, most researchers are inclining to the dithiolmethylamine ligand.…”

“…On the basis of mechanistic considerations, most researchers are inclining to the dithiolmethylamine ligand. However, a recent X-ray crystallographic study of CpI in combination with a theoretical study favored a dithiomethyl ether ligand [24].…”

How oxygen attacks [FeFe] hydrogenases from photosynthetic organisms

“…An unusual dithiolate ligand, originally modeled as a 1,3 propane dithiolate, forms a bridge between Fe p and Fe d . In the oxidized state H ox , as determined from the structure of the CpI enzyme from Clostridium pasteurianum, Fe p is also coordinated by one CO and one CN Ϫ ligand and shares a bridging CO with Fe d (11,12). The distal Fe is also coordinated by one CO and one CN Ϫ ligand, and an additional binding site is vacant (9) or occupied by an exchangeable O ligand, most likely a water molecule (11).…”

Mechanism of Proton Transfer in [FeFe]-Hydrogenase from Clostridium pasteurianum

“…1A) (17,18) and Desulfovibrio desulfuricans (19)), and there is considerable structural homology near the active site. This active site (H-cluster) is best described as a [4Fe4S]-cubane cluster attached via a cysteinyl sulfur linkage to a diiron moiety.…”