QM/MM computations reveal details of the acetyl-CoA synthase catalytic center.

The "open" (A) and "closed" (A) A-clusters of the acteyl-CoA synthase (ACS) enzyme from Moorella thermoacetica have been studied using a combined quantum mechanical (QM)/molecular mechanical (MM) approach. Geometry optimizations of the oxidized, one- and two-electron reduced A state have been carried out for the fully solvated ACS enzyme, and the CO ligand has been modeled in the reduced models. Using a combination of both α and α protein scaffolds and the positions of metal atoms in these structures, we have been able to piece together critical parts of the catalytic cycle of ACS.

Proton Transfer Pathways between Active Sites and Proximal Clusters in the Membrane-Bound [NiFe] Hydrogenase.

[NiFe] hydrogenases are enzymes that catalyze the splitting of molecular hydrogen according to the reaction H → 2H + 2e. Most of these enzymes are inhibited even by low traces of O. However, a special group of O-tolerant hydrogenases exists.

Carbon Monoxide Dehydrogenase Reduces Cyanate to Cyanide.

The biocatalytic function of carbon monoxide dehydrogenase (CODH) has a high environmental relevance owing to its ability to reduce CO . Despite numerous studies on CODH over the past decades, its catalytic mechanism is not yet fully understood. In the present combined spectroscopic and theoretical study, we report first evidences for a cyanate (NCO ) to cyanide (CN ) reduction at the C-cluster.

When the inhibitor tells more than the substrate: the cyanide-bound state of a carbon monoxide dehydrogenase.

Carbon monoxide dehydrogenase (CODH) is a key enzyme for reversible CO interconversion. To elucidate structural and mechanistic details of CO binding at the CODH active site (C-cluster), cyanide is frequently used as an iso-electronic substitute and inhibitor. However, previous studies revealed conflicting results on the structure of the cyanide-bound complex and the mechanism of cyanide-inhibition.