Metal–Dithiolene Bonding Contributions to Pyranopterin Molybdenum Enzyme Reactivity

Abstract

Here we highlight past work on metal–dithiolene interactions and how the unique electronic structure of the metal–dithiolene unit contributes to both the oxidative and reductive half reactions in pyranopterin molybdenum and tungsten enzymes. The metallodithiolene electronic structures detailed here were interrogated using multiple ground and excited state spectroscopic probes on the enzymes and their small molecule analogs. The spectroscopic results have been interpreted in the context of bonding and spectroscopic calculations, and the pseudo-Jahn–Teller effect. The dithiolene is a unique ligand with respect to its redox active nature, electronic synergy with the pyranopterin component of the molybdenum cofactor, and the ability to undergo chelate ring distortions that control covalency, reduction potential, and reactivity in pyranopterin molybdenum and tungsten enzymes.

Addressing Serine Lability in a Paramagnetic Dimethyl Sulfoxide Reductase Catalytic Intermediate

“… ,,− The g 1 values observed for the models are slightly higher than those observed for high-g split . 22 A clear explanation for this trend is complicated by the combined effects of small changes in the Mo–S covalency, ,,− interdithiolene twist angles, and orientation of the O ligands bound to Mo on the spin-Hamiltonian parameters . We note that the magnitude of ⟨ A Mo ⟩ for the models is slightly less than that observed for high-g split , and this likely reflects marginally higher metal–ligand covalencies in the models. , Notwithstanding, the remarkable similarity of the g - and A -tensor components for the enzymes and models strongly argue for Mo coordination spheres that only differ slightly in geometry.…”

A bacterial tungsten-containing aldehyde oxidoreductase forms an enzymatic decorated protein nanowire

“…The best candidate structure for the density available corresponds to the oxidised version of cofactor (W(VI)) containing two oxo ligands. Based on the observed distorted octahedral cofactor geometry and the known differences in pterin geometries between oxidised and reduced cofactor models ( 24, 25 ), we infer an oxidised state of the W-cofactor in the available density maps. The presence of two oxo ligands is also in good agreement with the available spectroscopic data for AOR Pf ( 26, 27 ).…”

Bringing Nitric Oxide to the Molybdenum World—A Personal Perspective

“…Molybdenum-containing enzymes are responsible for the biological handling of dinitrogen (Nitrogenase, Equation ( 1)), nitrate (Nitrate reductase (NaR), Equation ( 2)), sulfite (Sulfite oxidase (SO), Equation ( 3)), dimethylsulfoxide (dimethylsulfoxide reductase (DMSOR), Equation ( 4)), aldehydes (Aldehyde oxidase (AO), Equation ( 5)), xanthine (Xanthine oxidase (XO), Equation ( 6)) and carbon dioxide (Carbon dioxide dehydrogenase, Equation (7), and Formate dehydrogenase, Equation ( 8 With the single (as far as is presently known) exception of nitrogenase [9][10][11][12], molybdenum is found coordinated by the cis-dithiolene group (-S-C=C-S-) of one or two molecules of a pyranopterin cofactor (Figure 1). In a parallel situation to the haem ring, this unique cofactor is not an "innocent scaffold" and it is considered to be co-responsible to modulate the active site reactivity, besides acting as a "wire" to conduct the electrons to, or from, the other redox-active centres of the enzyme (intramolecular electron transfer, when this is the case) [13][14][15][16][17][18][19][20]. In addition to the pyranopterin cofactor, the molybdenum ion is coordinated by oxygen and/or sulfur and/or selenium terminal atoms and/or by enzyme-derived amino acid residues (Figure 1), which are also expected to have key roles in catalysis (although their individual roles are not yet understood in many molybdoenzymes).…”