Noninnocent Dithiolene Ligands: A New Oxomolybdenum Complex Possessing a Donor−Acceptor Dithiolene Ligand

The conserved pterin dithiolene ligand that coordinates molybdenum (Mo) in the cofactor (Moco) of mononuclear Mo enzymes can exist in both a tricyclic pyranopterin dithiolene form and as a bicyclic pterin-dithiolene form as observed in protein crystal structures of several bacterial molybdoenzymes. Interconversion between the tricyclic and bicyclic forms via pyran scission and cyclization has been hypothesized to play a role in the catalytic mechanism of Moco. Therefore understanding the interconversion between the tricyclic and bicyclic forms, a type of ring-chain tautomerism, is an important aspect of study in order to understand its role in catalysis. In this study, equilibrium constants (Keq) as well as enthalpy, entropy, and free energy values are obtained for pyran ring tautomerism exhibited by two Moco model complexes, (Et4N)[Tp*Mo(O)(S2BMOPP)] (1) and (Et4N)[Tp*Mo(O)(S2PEOPP)] (2), as a solvent-dependent equilibrium process. Keq values obtained from 1H NMR data in seven deuterated solvents show a correlation between solvent polarity and tautomer form, where solvents with higher polarity parameters favor the pyran form.

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“…Quinoxaline rotation precedes an intramolecular cyclization process to form a pyrrolo-dithiolene ligand. 42,43 …”

Section: Resultsmentioning

confidence: 99%

Solvent-Dependent Pyranopterin Cyclization in Molybdenum Cofactor Model Complexes

et al. 2015

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“…Dithiolenes display remarkable non-innocent behavior in small molecule analogues of pyranopterin Mo active sites (9)(10)(11). This non-innocence extends the redox cycling of the metal through its VI/V/IV oxidation states to include two electron redox reactions of the dithiolene ligand via access to the reduced ene-dithiolate, radical dithiolene, and oxidized dithione forms (12)(13)(14).…”

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confidence: 96%

Pyranopterin conformation defines the function of molybdenum and tungsten enzymes

Rothery

Stein

Solomonson

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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We have analyzed the conformations of 319 pyranopterins in 102 protein structures of mononuclear molybdenum and tungsten enzymes. These span a continuum between geometries anticipated for quinonoid dihydro, tetrahydro, and dihydro oxidation states. We demonstrate that pyranopterin conformation is correlated with the protein folds defining the three major mononuclear molybdenum and tungsten enzyme families, and that binding-site microtuning controls pyranopterin oxidation state. Enzymes belonging to the bacterial dimethyl sulfoxide reductase (DMSOR) family contain a metal-bis-pyranopterin cofactor, the two pyranopterins of which have distinct conformations, with one similar to the predicted tetrahydro form, and the other similar to the predicted dihydro form. Enzymes containing a single pyranopterin belong to either the xanthine dehydrogenase (XDH) or sulfite oxidase (SUOX) families, and these have pyranopterin conformations similar to those predicted for tetrahydro and dihydro forms, respectively. This work provides keen insight into the roles of pyranopterin conformation and oxidation state in catalysis, redox potential modulation of the metal site, and catalytic function.energetics | molybdoenzymes | redox chemistry T he pyranopterin dithiolene ligand is present in all molybdenum (Mo) and tungsten (W) containing enzymes with the exception of nitrogenase (1). These enzymes, known as mononuclear Mo/W enzymes, play pivotal roles in metabolism, global geochemical cycles, and microbial metabolic diversity (2-5). Their active sites, comprising a Mo or W ion and one or two pyranopterins, catalyze a diversity of redox transformations spanning a reduction potential range of approximately one volt. While the immediate environment of the substrate-binding metal ion is critically important in catalysis (6), little attention has been focused on the impact of variations in pyranopterin structure on enzyme function.Protein-bound pyranopterins are typically interpreted as having the tricyclic structure depicted in Fig. 1A, comprising pyrimidine, piperazine, and pyran-dithiolene rings. The dithiolene chelate binds a single Mo/W atom, which constitutes the catalytic active site. The pyranopterin shown in Fig. 1A is also known as the tetrahydro mononucleotide form due to the oxidation state of its piperazine ring and the presence of a phosphomethyl group attached to its C-2 atom (1). This form is assigned to the xanthine dehydrogenases, and in its cytosine dinucleotide form to the bacterial carbon monoxide dehydrogenases and aldehyde dehydrogenases (these enzymes are referred to collectively as the XDH family). It is also assigned to the sulfite oxidases and plant nitrate reductases [SUOX family (1, 5)].Mononuclear Mo/W enzymes also coordinate metal-bis-pyranopterin cofactors, either as the metal-bis(pyranopterin guanine dinucleotide) form (Fig. 1D) found in the dimethyl sulfoxide reductase family of molybdoenzyme subunits (DMSOR family), or the mononuclear bis-pyranopterin form found in the thermophilic aldehyde oxidoreductases...

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“…If the role of the pyranopterin dithiolene chelates is merely to contribute to a molybdenum-binding scaffold at the active site, then variants of the target residues studied herein should have little or no effect on enzyme function. If, however, the noninnocence reported for model compounds extends beyond the dithiolene chelate and into the heterocyclic ring system of the pyanopterin (13)(14)(15)20), variants of pyranopterin-coordinating residues should have a dramatic effect on molybdenum electrochemistry and catalysis.…”

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Pyranopterin Coordination Controls Molybdenum Electrochemistry in Escherichia coli Nitrate Reductase

Rothery

Weiner

2015

Journal of Biological Chemistry

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Background:The role of the pyranopterin component of the mononuclear molybdenum cofactor is largely unknown. Results: Variants of pyranopterin-coordinating amino acid residues were generated, and their effects on electrochemistry/ catalysis investigated. Conclusion:The pyranopterin environment modulates molybdenum electrochemistry. Significance: The pyranopterin coordination environment enables redox-tuning of the molybdenum atom, and facilitates molybdoenzyme reactivity toward a broad range of substrates.

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Noninnocent Dithiolene Ligands: A New Oxomolybdenum Complex Possessing a Donor−Acceptor Dithiolene Ligand

Cited by 41 publications

References 22 publications

Solvent-Dependent Pyranopterin Cyclization in Molybdenum Cofactor Model Complexes

Solvent-Dependent Pyranopterin Cyclization in Molybdenum Cofactor Model Complexes

Pyranopterin conformation defines the function of molybdenum and tungsten enzymes

Pyranopterin Coordination Controls Molybdenum Electrochemistry in Escherichia coli Nitrate Reductase

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