Variation in human gut microbiota impacts tamoxifen pharmacokinetics.

Tamoxifen is the most prescribed drug used to prevent breast cancer recurrence, but patients show variable responses to tamoxifen. Such differential inter-individual response has a significant socioeconomic impact as one in eight women will develop breast cancer and nearly half a million people in the United States are treated with tamoxifen annually. Tamoxifen is orally delivered and must be activated by metabolizing enzymes in the liver; however, clinical studies show that neither genotype nor hepatic metabolic enzymes are sufficient to predict why some patients have sub-therapeutic levels of the drug.

Mechanism of Action of Formate Dehydrogenases.

The molybdenum- and tungsten-containing formate dehydrogenases from a variety of microorganisms catalyze the reversible interconversion of formate and CO; several, in fact, function as CO reductases in the reverse direction under physiological conditions. CO reduction catalyzed by these enzymes occurs under mild temperature and pressure rather than the elevated conditions required for current industrial processes. Given the contemporary importance of remediation of atmospheric CO to address global warming, there has been considerable interest in the application of these enzymes in bioreactors.

Redox Characterization of the Complex Molybdenum Enzyme Formate Dehydrogenase from .

The oxygen-tolerant and molybdenum-dependent formate dehydrogenase FdsDABG from is capable of catalyzing both formate oxidation to CO and the reverse reaction (CO reduction to formate) at neutral pH, which are both reactions of great importance to energy production and carbon capture. FdsDABG is replete with redox cofactors comprising seven Fe/S clusters, flavin mononucleotide, and a molybdenum ion coordinated by two pyranopterin dithiolene ligands. The redox potentials of these centers are described herein and assigned to specific cofactors using combinations of potential-dependent continuous wave and pulse EPR spectroscopy and UV/visible spectroelectrochemistry on both the FdsDABG holoenzyme and the FdsBG subcomplex.

The Reversible Electrochemical Interconversion of Formate and CO by Formate Dehydrogenase from .

The bacterial molybdenum (Mo)-containing formate dehydrogenase (FdsDABG) from is a soluble NAD-dependent enzyme belonging to the DMSO reductase family. The holoenzyme is complex and possesses nine redox-active cofactors including a bis(molybdopterin guanine dinucleotide) (bis-MGD) active site, seven iron-sulfur clusters, and 1 equiv of flavin mononucleotide (FMN). FdsDABG catalyzes the two-electron oxidation of HCOO (formate) to CO and reversibly reduces CO to HCOO under physiological conditions close to its thermodynamic redox potential.

The air-inactivation of formate dehydrogenase FdsDABG from Cupriavidus necator.

The nature of air-inactivation of the formate dehydrogenase FdsDABG from Cupriavidus necator has been investigated. It is found that superoxide, generated in the reaction of reduced enzyme with oxygen, is responsible for the loss of activity and that superoxide dismutase protects the enzyme from air-inactivation. Inhibition appears to be due to the reaction of superoxide with the catalytically essential MoS group of the enzyme's molybdenum center in such a way that generates sulfite.

Crystallographic and kinetic analyses of the FdsBG subcomplex of the cytosolic formate dehydrogenase FdsABG from .

Formate oxidation to carbon dioxide is a key reaction in one-carbon compound metabolism, and its reverse reaction represents the first step in carbon assimilation in the acetogenic and methanogenic branches of many anaerobic organisms. The molybdenum-containing dehydrogenase FdsABG is a soluble NAD-dependent formate dehydrogenase and a member of the NADH dehydrogenase superfamily. Here, we present the first structure of the FdsBG subcomplex of the cytosolic FdsABG formate dehydrogenase from the hydrogen-oxidizing bacterium H16 both with and without bound NADH.