Special Issue "Transition Metals in Catalysis: The Functional Relationship of Fe–S Clusters and Molybdenum or Tungsten Cofactor-Containing Enzyme Systems"

A special issue of Inorganics (ISSN 2304-6740). This special issue belongs to the section "Bioinorganic Chemistry".

Deadline for manuscript submissions: closed (30 June 2020).

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. Silke Leimkühler
E-Mail Website
Guest Editor
Department of Molecular Enzymology, Institute of Biochemistry and Biology, University of Potsdam, Potsdam, Germany
Interests: molybdenum cofactor; catalytic mechanism of molybdoenzymes; crosstalk of Fe–S cluster assembly and Moco biosynthesis; sulfur-containing cofactors
Prof. Dr. Axel Magalon
E-Mail Website
Guest Editor
Laboratoire de Chimie Bacterienne, Aix-Marseille University & CNRS, Marseille, France
Interests: metabolism; metalloenzymes; molybdenum cofactor; membrane proteins; nitrogen cycle
Prof. Dr. Oliver Einsle
E-Mail Website
Guest Editor
Institute for Biochemistry, Albert-Ludwigs-University Freiburg, Freiburg, Germany
Interests: structural biology; metalloenzymes; membrane proteins; biological nitrogen fixation; iron–sulfur enzymes; cofactor biogenesis; nitrogen cycle; metabolism
Prof. Dr. Carola Schulzke
E-Mail Website
Guest Editor
Institute for Biochemistry, University Greifswald, Greifswald, Germany
Interests: bioinorganic chemistry; molybdenum and tungsten cofactors; vanadium; model synthesis; X-ray diffraction; oxygen atom transfer; organometallic catalysis; pentathiepins; structure–function relationships

Special Issue Information

Dear Colleagues,

Following the Molybdenum and Tungsten Enzyme conference “MoTEC” and the satellite meeting on “Iron-Sulfur for Life”, we kindly invite you to submit a research paper to this Special Issue of Inorganics entitled “Transition Metals in Catalysis: The Functional Relationship of Fe–S Clusters and Molybdenum or Tungsten Cofactor-Containing Enzyme Systems”. Contributions should study enzyme mechanisms, innovative model complexes, and biogenesis pathways that are interconnected by distinct metal ions, in particular, molybdenum, tungsten, and iron. The particular focus is on molybdenum and tungsten cofactor-containing enzyme systems, nitrogenase and Fe–S cluster assembly, and insertion into enzymes. We encourage everyone within these research fields to submit an article so that we can compile a comprehensive Special Issue that may inspire future research directions.

Prof. Dr. Silke Leimkühler
Prof. Dr. Axel Magalon
Prof. Dr. Oliver Einsle
Prof. Dr. Carola Schulzke
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Inorganics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Fe–S cluster assembly
  • molybdenum and tungsten cofactor biosynthesis
  • molybdoenzymes
  • tungstoenzymes
  • nitrogenase
  • bioinspired complexes
  • biomimetic catalysis
  • spectroscopy

Published Papers (10 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

Editorial
Transition Metals in Catalysis: The Functional Relationship of Fe–S Clusters and Molybdenum or Tungsten Cofactor-Containing Enzyme Systems
Inorganics 2021, 9(1), 6; https://doi.org/10.3390/inorganics9010006 - 13 Jan 2021
Viewed by 496
Abstract
Following the “Molybdenum and Tungsten Enzyme conference—MoTEC2019” and the satellite meeting on “Iron–Sulfur for Life”, we wanted to emphasize the link between iron–sulfur clusters and their importance for the biosynthesis, assembly, and activity of complex metalloenzymes in this Special Issue of Inorganics, [...] Read more.
Following the “Molybdenum and Tungsten Enzyme conference—MoTEC2019” and the satellite meeting on “Iron–Sulfur for Life”, we wanted to emphasize the link between iron–sulfur clusters and their importance for the biosynthesis, assembly, and activity of complex metalloenzymes in this Special Issue of Inorganics, entitled “Transition Metals in Catalysis: The Functional Relationship of Fe–S Clusters and Molybdenum or Tungsten Cofactor-Containing Enzyme Systems” [...] Full article

Research

Jump to: Editorial, Review

Article
Crystal Structures of [Fe]-Hydrogenase from Methanolacinia paynteri Suggest a Path of the FeGP-Cofactor Incorporation Process
Inorganics 2020, 8(9), 50; https://doi.org/10.3390/inorganics8090050 - 17 Sep 2020
Cited by 1 | Viewed by 823
Abstract
[Fe]-hydrogenase (Hmd) catalyzes the reversible heterolytic cleavage of H2, and hydride transfer to methenyl-tetrahydromethanopterin (methenyl-H4MPT+). The iron-guanylylpyridinol (FeGP) cofactor, the prosthetic group of Hmd, can be extracted from the holoenzyme and inserted back into the protein. Here, [...] Read more.
[Fe]-hydrogenase (Hmd) catalyzes the reversible heterolytic cleavage of H2, and hydride transfer to methenyl-tetrahydromethanopterin (methenyl-H4MPT+). The iron-guanylylpyridinol (FeGP) cofactor, the prosthetic group of Hmd, can be extracted from the holoenzyme and inserted back into the protein. Here, we report the crystal structure of an asymmetric homodimer of Hmd from Methanolacinia paynteri (pHmd), which was composed of one monomer in the open conformation with the FeGP cofactor (holo-form) and a second monomer in the closed conformation without the cofactor (apo-form). In addition, we report the symmetric pHmd-homodimer structure in complex with guanosine monophosphate (GMP) or guanylylpyridinol (GP), in which each ligand was bound to the protein, where the GMP moiety of the FeGP-cofactor is bound in the holo-form. Binding of GMP and GP modified the local protein structure but did not induce the open conformation. The amino-group of the Lys150 appears to interact with the 2-hydroxy group of pyridinol ring in the pHmd–GP complex, which is not the case in the structure of the pHmd–FeGP complex. Lys150Ala mutation decreased the reconstitution rate of the active enzyme with the FeGP cofactor at the physiological pH. These results suggest that Lys150 might be involved in the FeGP-cofactor incorporation into the Hmd protein in vivo. Full article
Show Figures

Graphical abstract

Article
Susceptibility of the Formate Hydrogenlyase Reaction to the Protonophore CCCP Depends on the Total Hydrogenase Composition
Inorganics 2020, 8(6), 38; https://doi.org/10.3390/inorganics8060038 - 28 May 2020
Cited by 1 | Viewed by 977
Abstract
Fermentative hydrogen production by enterobacteria derives from the activity of the formate hydrogenlyase (FHL) complex, which couples formate oxidation to H2 production. The molybdenum-containing formate dehydrogenase and type-4 [NiFe]-hydrogenase together with three iron-sulfur proteins form the soluble domain, which is attached to [...] Read more.
Fermentative hydrogen production by enterobacteria derives from the activity of the formate hydrogenlyase (FHL) complex, which couples formate oxidation to H2 production. The molybdenum-containing formate dehydrogenase and type-4 [NiFe]-hydrogenase together with three iron-sulfur proteins form the soluble domain, which is attached to the membrane by two integral membrane subunits. The FHL complex is phylogenetically related to respiratory complex I, and it is suspected that it has a role in energy conservation similar to the proton-pumping activity of complex I. We monitored the H2-producing activity of FHL in the presence of different concentrations of the protonophore CCCP. We found an inhibition with an apparent EC50 of 31 µM CCCP in the presence of glucose, a higher tolerance towards CCCP when only the oxidizing hydrogenase Hyd-1 was present, but a higher sensitivity when only Hyd-2 was present. The presence of 200 mM monovalent cations reduced the FHL activity by more than 20%. The Na+/H+ antiporter inhibitor 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) combined with CCCP completely inhibited H2 production. These results indicate a coupling not only between Na+ transport activity and H2 production activity, but also between the FHL reaction, proton import and cation export. Full article
Show Figures

Graphical abstract

Article
A Mixed-Valence Tetra-Nuclear Nickel Dithiolene Complex: Synthesis, Crystal Structure, and the Lability of Its Nickel Sulfur Bonds
Inorganics 2020, 8(4), 27; https://doi.org/10.3390/inorganics8040027 - 09 Apr 2020
Cited by 2 | Viewed by 970
Abstract
In this study, by employing a common synthetic protocol, an unusual and unexpected tetra-nuclear nickel dithiolene complex was obtained. The synthesis of the [Ni4(ecpdt)6]2− dianion (ecpdt = (Z)-3-ethoxy-3-oxo-1-phenylprop-1-ene-1,2-bis-thiolate) with two K+ as counter ions was [...] Read more.
In this study, by employing a common synthetic protocol, an unusual and unexpected tetra-nuclear nickel dithiolene complex was obtained. The synthesis of the [Ni4(ecpdt)6]2− dianion (ecpdt = (Z)-3-ethoxy-3-oxo-1-phenylprop-1-ene-1,2-bis-thiolate) with two K+ as counter ions was then intentionally reproduced. The formation of this specific complex is attributed to the distinct dithiolene precursor used and the combination with the then coordinated counter ion in the molecular solid-state structure, as determined by X-ray diffraction. K2[Ni4(ecpdt)6] was further characterized by ESI-MS, FT-IR, UV-Vis, and cyclic voltammetry. The tetra-nuclear complex was found to have an uncommon geometry arising from the combination of four nickel centers and six dithiolene ligands. In the center of the arrangement, suspiciously long Ni–S distances were found, suggesting that the tetrameric structure can be easily split into two identical dimeric fragments or two distinct groups of monomeric fragments, for instance, upon dissolving. A proposed variable magnetism in the solid-state and in solution due to the postulated dissociation was confirmed. The Ni–S bonds of the “inner” and “outer” nickel centers differed concurrently with their coordination geometries. This observation also correlates with the fact that the complex bears two anionic charges requiring the four nickel centers to be present in two distinct oxidation states (2 × +2 and 2 × +3), i.e., to be hetero-valent. The different coordination geometries observed, together with the magnetic investigation, allowed the square planar “outer” geometry to be assigned to d8 centers, i.e., Ni2+, while the Ni3+ centers (d7) were in a square pyramidal geometry with longer Ni–S distances due to the increased number of donor atoms and interactions. Full article
Show Figures

Graphical abstract

Article
Theoretical Insights into the Aerobic Hydrogenase Activity of Molybdenum–Copper CO Dehydrogenase
Inorganics 2019, 7(11), 135; https://doi.org/10.3390/inorganics7110135 - 09 Nov 2019
Cited by 2 | Viewed by 1098
Abstract
The Mo/Cu-dependent CO dehydrogenase from O. carboxidovorans is an enzyme that is able to catalyse CO oxidation to CO 2 ; moreover, it also expresses hydrogenase activity, as it is able to oxidize H 2 . Here, we have studied the dihydrogen oxidation catalysis by this enzyme using QM/MM calculations. Our results indicate that the equatorial oxo ligand of Mo is the best suited base for catalysis. Moreover, extraction of the first proton from H 2 by means of this basic centre leads to the formation of a Mo–OH–Cu I H hydride that allows for the stabilization of the copper hydride, otherwise known to be very unstable. In light of our results, two mechanisms for the hydrogenase activity of the enzyme are proposed. The first reactive channel depends on protonation of the sulphur atom of a Cu-bound cysteine residues, which appears to favour the binding and activation of the substrate. The second reactive channel involves a frustrated Lewis pair, formed by the equatorial oxo group bound to Mo and by the copper centre. In this case, no binding of the hydrogen molecule to the Cu center is observed but once H 2 enters into the active site, it can be split following a low-energy path. Full article
Show Figures

Figure 1

Review

Jump to: Editorial, Research

Review
Mechanism of Iron–Sulfur Cluster Assembly: In the Intimacy of Iron and Sulfur Encounter
Inorganics 2020, 8(10), 55; https://doi.org/10.3390/inorganics8100055 - 03 Oct 2020
Cited by 4 | Viewed by 1203
Abstract
Iron–sulfur (Fe–S) clusters are protein cofactors of a multitude of enzymes performing essential biological functions. Specialized multi-protein machineries present in all types of organisms support their biosynthesis. These machineries encompass a scaffold protein on which Fe–S clusters are assembled and a cysteine desulfurase [...] Read more.
Iron–sulfur (Fe–S) clusters are protein cofactors of a multitude of enzymes performing essential biological functions. Specialized multi-protein machineries present in all types of organisms support their biosynthesis. These machineries encompass a scaffold protein on which Fe–S clusters are assembled and a cysteine desulfurase that provides sulfur in the form of a persulfide. The sulfide ions are produced by reductive cleavage of the persulfide, which involves specific reductase systems. Several other components are required for Fe–S biosynthesis, including frataxin, a key protein of controversial function and accessory components for insertion of Fe–S clusters in client proteins. Fe–S cluster biosynthesis is thought to rely on concerted and carefully orchestrated processes. However, the elucidation of the mechanisms of their assembly has remained a challenging task due to the biochemical versatility of iron and sulfur and the relative instability of Fe–S clusters. Nonetheless, significant progresses have been achieved in the past years, using biochemical, spectroscopic and structural approaches with reconstituted system in vitro. In this paper, we review the most recent advances on the mechanism of assembly for the founding member of the Fe–S cluster family, the [2Fe2S] cluster that is the building block of all other Fe–S clusters. The aim is to provide a survey of the mechanisms of iron and sulfur insertion in the scaffold proteins by examining how these processes are coordinated, how sulfide is produced and how the dinuclear [2Fe2S] cluster is formed, keeping in mind the question of the physiological relevance of the reconstituted systems. We also cover the latest outcomes on the functional role of the controversial frataxin protein in Fe–S cluster biosynthesis. Full article
Show Figures

Figure 1

Review
Tungstoenzymes: Occurrence, Catalytic Diversity and Cofactor Synthesis
Inorganics 2020, 8(8), 44; https://doi.org/10.3390/inorganics8080044 - 31 Jul 2020
Cited by 2 | Viewed by 969
Abstract
Tungsten is the heaviest element used in biological systems. It occurs in the active sites of several bacterial or archaeal enzymes and is ligated to an organic cofactor (metallopterin or metal binding pterin; MPT) which is referred to as tungsten cofactor (Wco). Wco-containing [...] Read more.
Tungsten is the heaviest element used in biological systems. It occurs in the active sites of several bacterial or archaeal enzymes and is ligated to an organic cofactor (metallopterin or metal binding pterin; MPT) which is referred to as tungsten cofactor (Wco). Wco-containing enzymes are found in the dimethyl sulfoxide reductase (DMSOR) and the aldehyde:ferredoxin oxidoreductase (AOR) families of MPT-containing enzymes. Some depend on Wco, such as aldehyde oxidoreductases (AORs), class II benzoyl-CoA reductases (BCRs) and acetylene hydratases (AHs), whereas others may incorporate either Wco or molybdenum cofactor (Moco), such as formate dehydrogenases, formylmethanofuran dehydrogenases or nitrate reductases. The obligately tungsten-dependent enzymes catalyze rather unusual reactions such as ones with extremely low-potential electron transfers (AOR, BCR) or an unusual hydration reaction (AH). In recent years, insights into the structure and function of many tungstoenzymes have been obtained. Though specific and unspecific ABC transporter uptake systems have been described for tungstate and molybdate, only little is known about further discriminative steps in Moco and Wco biosynthesis. In bacteria producing Moco- and Wco-containing enzymes simultaneously, paralogous isoforms of the metal insertase MoeA may be specifically involved in the molybdenum- and tungsten-insertion into MPT, and in targeting Moco or Wco to their respective apo-enzymes. Wco-containing enzymes are of emerging biotechnological interest for a number of applications such as the biocatalytic reduction of CO2, carboxylic acids and aromatic compounds, or the conversion of acetylene to acetaldehyde. Full article
Show Figures

Graphical abstract

Review
The Requirement of Inorganic Fe-S Clusters for the Biosynthesis of the Organometallic Molybdenum Cofactor
Inorganics 2020, 8(7), 43; https://doi.org/10.3390/inorganics8070043 - 16 Jul 2020
Cited by 1 | Viewed by 1094
Abstract
Iron-sulfur (Fe-S) clusters are essential protein cofactors. In enzymes, they are present either in the rhombic [2Fe-2S] or the cubic [4Fe-4S] form, where they are involved in catalysis and electron transfer and in the biosynthesis of metal-containing prosthetic groups like the molybdenum cofactor [...] Read more.
Iron-sulfur (Fe-S) clusters are essential protein cofactors. In enzymes, they are present either in the rhombic [2Fe-2S] or the cubic [4Fe-4S] form, where they are involved in catalysis and electron transfer and in the biosynthesis of metal-containing prosthetic groups like the molybdenum cofactor (Moco). Here, we give an overview of the assembly of Fe-S clusters in bacteria and humans and present their connection to the Moco biosynthesis pathway. In all organisms, Fe-S cluster assembly starts with the abstraction of sulfur from l-cysteine and its transfer to a scaffold protein. After formation, Fe-S clusters are transferred to carrier proteins that insert them into recipient apo-proteins. In eukaryotes like humans and plants, Fe-S cluster assembly takes place both in mitochondria and in the cytosol. Both Moco biosynthesis and Fe-S cluster assembly are highly conserved among all kingdoms of life. Moco is a tricyclic pterin compound with molybdenum coordinated through its unique dithiolene group. Moco biosynthesis begins in the mitochondria in a Fe-S cluster dependent step involving radical/S-adenosylmethionine (SAM) chemistry. An intermediate is transferred to the cytosol where the dithiolene group is formed, to which molybdenum is finally added. Further connections between Fe-S cluster assembly and Moco biosynthesis are discussed in detail. Full article
Show Figures

Figure 1

Review
Structure: Function Studies of the Cytosolic, Mo- and NAD+-Dependent Formate Dehydrogenase from Cupriavidus necator
Inorganics 2020, 8(7), 41; https://doi.org/10.3390/inorganics8070041 - 06 Jul 2020
Cited by 3 | Viewed by 748
Abstract
Here, we report recent progress our laboratories have made in understanding the maturation and reaction mechanism of the cytosolic and NAD+-dependent formate dehydrogenase from Cupriavidus necator. Our recent work has established that the enzyme is fully capable of catalyzing the reverse [...] Read more.
Here, we report recent progress our laboratories have made in understanding the maturation and reaction mechanism of the cytosolic and NAD+-dependent formate dehydrogenase from Cupriavidus necator. Our recent work has established that the enzyme is fully capable of catalyzing the reverse of the physiological reaction, namely, the reduction of CO2 to formate using NADH as a source of reducing equivalents. The steady-state kinetic parameters in the forward and reverse directions are consistent with the expected Haldane relationship. The addition of an NADH-regenerating system consisting of glucose and glucose dehydrogenase increases the yield of formate approximately 10-fold. This work points to possible ways of optimizing the reverse of the enzyme’s physiological reaction with commercial potential as an effective means of CO2 remediation. New insight into the maturation of the enzyme comes from the recently reported structure of the FdhD sulfurase. In E. coli, FdhD transfers a catalytically essential sulfur to the maturing molybdenum cofactor prior to insertion into the apoenzyme of formate dehydrogenase FdhF, which has high sequence similarity to the molybdenum-containing domain of the C. necator FdsA. The FdhD structure suggests that the molybdenum cofactor may first be transferred from the sulfurase to the C-terminal cap domain of apo formate dehydrogenase, rather than being transferred directly to the body of the apoenzyme. Closing of the cap domain over the body of the enzymes delivers the Mo-cofactor into the active site, completing the maturation of formate dehydrogenase. The structural and kinetic characterization of the NADH reduction of the FdsBG subcomplex of the enzyme provides further insights in reversing of the formate dehydrogenase reaction. Most notably, we observe the transient formation of a neutral semiquinone FMNH·, a species that has not been observed previously with holoenzyme. After initial reduction of the FMN of FdsB by NADH to the hydroquinone (with a kred of 680 s−1 and Kd of 190 µM), one electron is rapidly transferred to the Fe2S2 cluster of FdsG, leaving FMNH·. The Fe4S4 cluster of FdsB does not become reduced in the process. These results provide insight into the function not only of the C. necator formate dehydrogenase but also of other members of the NADH dehydrogenase superfamily of enzymes to which it belongs. Full article
Show Figures

Figure 1

Review
Metal–Dithiolene Bonding Contributions to Pyranopterin Molybdenum Enzyme Reactivity
Inorganics 2020, 8(3), 19; https://doi.org/10.3390/inorganics8030019 - 05 Mar 2020
Cited by 3 | Viewed by 1035
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 [...] Read more.
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. Full article
Show Figures

Figure 1

Back to TopTop