Structure, Function, and Mechanism of Pyranopterin Molybdenum and Tungsten Enzymes

Ingersol, Laura; Kirk, Martin L.

doi:10.1016/b978-0-12-409547-2.14929-7

Cited by 9 publications

(17 citation statements)

References 270 publications

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“…This study provides an unprecedented view into the special nature of the PDT ligand present in all molybdenum and tungsten enzymes. 1 The full suite of data from NMR, electronic absorption, and FT-IR spectroscopies, coupled with cyclic voltammetric and computational studies, has enabled a detailed description of 1-H. Protonation of 1 shifts the pyran ring opening equilibrium exclusively toward the cyclized pyranopterin structure in 1-H. Complex 1 has ∼30% thione-thiolate character in the dithiolene ligand, which redistributes electron density from one dithiolene sulfur atom to the partially oxidized pterin and increases the asymmetry within the chelate (Scheme 1). This resonance contribution results in a partial negative charge buildup on N5 (Figure 2, middle).…”

Section: ■ Relationship To Pyranopterin Mo Enzymesmentioning

confidence: 99%

“…The filtrate was immersion-filtered leaving a magenta solid that was washed twice with 25 mL of the hexane/ether mixture. The solid was dried under high vacuum to yield [Tp*Mo IV (O)(S 2 H-BMOPP)] (0.61 g, 61%) as a deep magenta solid: 1…”

Section: Synthesis Of [Tp*mo IV (O)(s 2 H-bmopp)] (1-h)mentioning

confidence: 99%

“…This study provides an unprecedented view into the special nature of the PDT ligand present in all molybdenum and tungsten enzymes . The full suite of data from NMR, electronic absorption, and FT-IR spectroscopies, coupled with cyclic voltammetric and computational studies, has enabled a detailed description of 1-H .…”

Section: Relationship To Pyranopterin Mo Enzymesmentioning

confidence: 99%

“…Molybdenum and tungsten are essential metals used for a broad range of geochemical and biochemical processes, including global C, N, and S cycles, respiration in bacteria, nitrogen assimilation in plants, and both sulfite detoxification and pro-drug conversion in humans. − Although pyranopterin-containing molybdenum enzymes are ubiquitous across nearly all organisms, the similar tungsten enzymes are only found in bacteria. ,,,− A pyranopterin dithiolene ligand (PDT), also known as molybdopterin (MPT), is found bound to Mo in all mononuclear Mo enzymes as the Mo cofactor, or Moco ,− (Figure top), and in the related W enzymes as the W cofactor. The PDT is an absolute requirement for a catalytically functional active site in the enzymes.…”

Section: Introductionmentioning

confidence: 99%

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Protonation and Non-Innocent Ligand Behavior in Pyranopterin Dithiolene Molybdenum Complexes

et al. 2022

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The complex [TEA][Tp*MoIV(O)(S2BMOPP)] (1) [TEA = tetraethylammonium, Tp* = tris(3,5-dimethylpyrazolyl)hydroborate, and BMOPP = 6-(3-butynyl-2-methyl-2-ol)-2-pivaloyl pterin] is a structural analogue of the molybdenum cofactor common to all pyranopterin molybdenum enzymes because it possesses a pyranopterin-ene-1,2-dithiolate ligand (S2BMOPP) that exists primarily in the ring-closed pyrano structure as a resonance hybrid of ene-dithiolate and thione-thiolate forms. Compound 1, the protonated [Tp*MoIV(O)(S2BMOPP-H)] (1-H) and one-electron-oxidized [Tp*MoV(O)(S2BMOPP)] [1-Mo(5+)] species have been studied using a combination of electrochemistry, electronic absorption, and electron paramagnetic resonance (EPR) spectroscopy. Additional insight into the nature of these molecules has been derived from electronic structure computations. Differences in dithiolene C–S bond lengths correlate with relative contributions from both ene-dithiolate and thione-thiolate resonance structures. Upon protonation of 1 to form 1-H, large spectroscopic changes are observed with transitions assigned as Mo(xy) → pyranopterin metal-to-ligand charge transfer and dithiolene → pyranopterin intraligand charge transfer, respectively, and this underscores a dramatic change in electronic structure between 1 and 1-H. The changes in electronic structure that occur upon protonation of 1 are also reflected in a large >300 mV increase in the Mo(V/IV) redox potential for 1-H, resulting from the greater thione-thiolate resonance contribution and decreased charge donation that stabilize the Mo(IV) state in 1-H with respect to one-electron oxidation. EPR spin Hamiltonian parameters for one-electron-oxidized 1-Mo(5+) and uncyclized [Tp*MoV(O)(S2BDMPP)] [3-Mo(5+)] [BDMPP = 6-(3-butynyl-2,2-dimethyl)-2-pivaloyl pterin] are very similar to each other and to those of [Tp*MoVO(bdt)] (bdt = 1,2-ene-dithiolate). This indicates that the dithiolate form of the ligand dominates at the Mo(V) level, consistent with the demand for greater S → Mo charge donation and a corresponding increase in Mo–S covalency as the oxidation state of the metal is increased. Protonation of 1 represents a simple reaction that models how the transfer of a proton from neighboring acidic amino acid residues to the Mo cofactor at a nitrogen atom within the pyranopterin dithiolene (PDT) ligand in pyranopterin molybdenum enzymes can impact the electronic structure of the Mo-PDT unit. This work also illustrates how pyran ring–chain tautomerization drives changes in resonance contributions to the dithiolene chelate and may adjust the reduction potential of the Mo ion.

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Section: ■ Relationship To Pyranopterin Mo Enzymesmentioning

confidence: 99%

Section: Synthesis Of [Tp*mo IV (O)(s 2 H-bmopp)] (1-h)mentioning

confidence: 99%

Section: Relationship To Pyranopterin Mo Enzymesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Protonation and Non-Innocent Ligand Behavior in Pyranopterin Dithiolene Molybdenum Complexes

et al. 2022

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“…Pyranopterin molybdenum enzymes are typically characterized as belonging to either the sulfite oxidase (SO), xanthine oxidase (XO), or dimethyl sulfoxide reductase enzyme families. − However, the molybdenum sulfurase C-terminal (MOSC) domain enzymes − represent a new family of molybdenum enzymes that do not possess any detectable homology with the original three canonical molybdenum enzyme families, although the MOSC domain proteins appear to possess active site structures that are reminiscent of SO family enzymes. A key difference between the MOSC domain enzymes and SO family enzymes is that the latter frequently fuse to cytochromes and do not have the [2Fe-2S] ferredoxin domains commonly seen in either the MOSC (e.g., the bacterial YcbX and YiiM proteins) or XO family enzymes.…”

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confidence: 99%

Active Site Structures of the Escherichia coli N-Hydroxylaminopurine Resistance Molybdoenzyme YcbX

et al. 2023

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X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) data have been used to characterize the coordination environment for the catalytic Mo site of Escherichia coli YcbX in two different oxidation states. In the oxidized state, the Mo(VI) ion is coordinated by two terminal oxo ligands, a thiolate S atom from cysteine, and two S donors from the bidentate pyranopterin ene-1,2-dithiolate (pyranopterin dithiolene). Upon reduction, it is the more basic equatorial oxo ligand that is protonated, with a Mo–Oeq bond distance that is best described as either a short Mo4+–OH2 bond or a long Mo4+–OH bond. Mechanistic implications for substrate reduction are discussed in light of these structural details.

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Active Site Characterization of a Campylobacter jejuni Nitrate Reductase Variant Provides Insight into the Enzyme Mechanism

Yang,

Mintmier,

et al. 2024

Inorg. Chem.

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Mo K-edge X-ray absorption spectroscopy (XAS) is used to probe the structure of wild-type Campylobacter jejuni nitrate reductase NapA and the C176A variant. The results of extended X-ray absorption fine structure (EXAFS) experiments on wt NapA support an oxidized Mo(VI) hexacoordinate active site coordinated by a single terminal oxo donor, four sulfur atoms from two separate pyranopterin dithiolene ligands, and an additional S atom from a conserved cysteine amino acid residue. We found no evidence of a terminal sulfido ligand in wt NapA. EXAFS analysis shows the C176A active site to be a 6-coordinate structure, and this is supported by EPR studies on C176A and small molecule analogs of Mo(V) enzyme forms. The S Cys is replaced by a hydroxide or water ligand in C176A, and we find no evidence of a coordinated sulfhydryl (SH) ligand. Kinetic studies show that this variant has completely lost its catalytic activity toward nitrate. Taken together, the results support a critical role for the conserved C176 in catalysis and an oxygen atom transfer mechanism for the catalytic reduction of nitrate to nitrite that does not employ a terminal sulfido ligand in the catalytic cycle.

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Structure, Function, and Mechanism of Pyranopterin Molybdenum and Tungsten Enzymes

Cited by 9 publications

References 270 publications

Protonation and Non-Innocent Ligand Behavior in Pyranopterin Dithiolene Molybdenum Complexes

Protonation and Non-Innocent Ligand Behavior in Pyranopterin Dithiolene Molybdenum Complexes

Active Site Structures of the Escherichia coli N-Hydroxylaminopurine Resistance Molybdoenzyme YcbX

Active Site Characterization of a Campylobacter jejuni Nitrate Reductase Variant Provides Insight into the Enzyme Mechanism

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