Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Key Structural Motifs Balance Metal Binding and Oxidative Reactivity in a Heterobimetallic Mn/Fe Protein.

ABSTRACT: Heterobimetallic Mn/Fe proteins represent a new cofactor paradigm in bioinorganic chemistry and pose countless outstanding questions. The assembly of the active site defies common chemical convention by contradicting the Irving-Williams series, while the scope of reactivity remains unexplored. In this work, the assembly and C-H bond activation process in the Mn/Fe R2-like ligand-binding oxidase (R2lox) protein is investigated using a suite of biophysical techniques, including time-resolved optical spectroscopy, global kinetic modeling, X-ray crystallography, electron paramagnetic resonance spectroscopy, protein electrochemistry, and mass spectrometry. Selective metal binding is found to be under thermodynamic control, with the binding sites within the apo-protein exhibiting greater Mn^II affinity than Fe^II affinity. The comprehensive analysis of structure and reactivity of wild-type R2lox and targeted primary and secondary sphere mutants indicate that the efficiency of C-H bond activation directly correlates with the Mn/Fe cofactor reduction potentials and is inversely related to divalent metal binding affinity. These findings suggest the R2lox active site is precisely tuned for achieving both selective heterobimetallic binding and high levels of reactivity and offer a mechanism to examine the means by which proteins achieve appropriate metal incorporation.

SUBMITTER: Kisgeropoulos EC

PROVIDER: S-EPMC7390604 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Chemical flexibility of heterobimetallic Mn/Fe cofactors: R2lox and R2c proteins.

Project description:A heterobimetallic Mn/Fe cofactor is present in the R2 subunit of class Ic ribonucleotide reductases (R2c) and in R2-like ligand-binding oxidases (R2lox). Although the protein-derived metal ligands are the same in both groups of proteins, the connectivity of the two metal ions and the chemistry each cofactor performs are different: in R2c, a one-electron oxidant, the Mn/Fe dimer is linked by two oxygen bridges (?-oxo/?-hydroxo), whereas in R2lox, a two-electron oxidant, it is linked by a single oxygen bridge (?-hydroxo) and a fatty acid ligand. Here, we identified a second coordination sphere residue that directs the divergent reactivity of the protein scaffold. We found that the residue that directly precedes the N-terminal carboxylate metal ligand is conserved as a glycine within the R2lox group but not in R2c. Substitution of the glycine with leucine converted the resting-state R2lox cofactor to an R2c-like cofactor, a ?-oxo/?-hydroxo-bridged MnIII/FeIII dimer. This species has recently been observed as an intermediate of the oxygen activation reaction in WT R2lox, indicating that it is physiologically relevant. Cofactor maturation in R2c and R2lox therefore follows the same pathway, with structural and functional divergence of the two cofactor forms following oxygen activation. We also show that the leucine-substituted variant no longer functions as a two-electron oxidant. Our results reveal that the residue preceding the N-terminal metal ligand directs the cofactor's reactivity toward one- or two-electron redox chemistry, presumably by setting the protonation state of the bridging oxygens and thereby perturbing the redox potential of the Mn ion.

| S-EPMC6885639 | biostudies-literature

Time-Resolved Investigations of Heterobimetallic Cofactor Assembly in R2lox Reveal Distinct Mn/Fe Intermediates.

Project description:The assembly mechanism of the Mn/Fe ligand-binding oxidases (R2lox), a family of proteins that are homologous to the nonheme diiron carboxylate enzymes, has been investigated using time-resolved techniques. Multiple heterobimetallic intermediates that exhibit unique spectral features, including visible absorption bands and exceptionally broad electron paramagnetic resonance signatures, are observed through optical and magnetic resonance spectroscopies. On the basis of comparison to known diiron species and model compounds, the spectra have been attributed to (?-peroxo)-MnIII/FeIII and high-valent Mn/Fe species. Global spectral analysis coupled with isotopic substitution and kinetic modeling reveals elementary rate constants for the assembly of Mn/Fe R2lox under aerobic conditions. A complete reaction mechanism for cofactor maturation that is consistent with experimental data has been developed. These results suggest that the Mn/Fe cofactor can perform direct C-H bond abstraction, demonstrating the potential for potent chemical reactivity that remains unexplored.

| S-EPMC5680038 | biostudies-literature

Heterobimetallic Complexes with MIII-(?-OH)-MII Cores (MIII = Fe, Mn, Ga; MII = Ca, Sr, and Ba): Structural, Kinetic, and Redox Properties.

Project description:The effects of redox-inactive metal ions on dioxygen activation were explored using a new FeII complex containing a tripodal ligand with 3 sulfonamido groups. This iron complex exhibited a faster initial rate for the reduction of O2 than its MnII analog. Increases in initial rates were also observed in the presence of group 2 metal ions for both the FeII and MnII complexes, which followed the trend NMe4+ < BaII < CaII = SrII. These studies led to the isolation of heterobimetallic complexes containing FeIII-(?-OH)-MII cores (MII = Ca, Sr, and Ba) and one with a [SrII(OH)MnIII]+ motif. The analogous [CaII(OH)GaIII]+ complex was also prepared and its solid state molecular structure is nearly identical to that of the [CaII(OH)FeIII]+ system. Nuclear magnetic resonance studies indicated that the diamagnetic [CaII(OH)GaIII]+ complex retained its structure in solution. Electrochemical measurements on the heterobimetallic systems revealed similar one-electron reduction potentials for the [CaII(OH)FeIII]+ and [SrII(OH)FeIII]+ complexes, which were more positive than the potential observed for [BaII(OH)FeIII]+. Similar results were obtained for the heterobimetallic MnII complexes. These findings suggest that Lewis acidity is not the only factor to consider when evaluating the effects of group 2 ions on redox processes, including those within the oxygen-evolving complex of Photosystem II.

| S-EPMC3777273 | biostudies-literature

Enhanced Fe-Centered Redox Flexibility in Fe-Ti Heterobimetallic Complexes.

Project description:Previously, we reported the synthesis of Ti[N( o-(NCH2P( iPr)2)C6H4)3] and the Fe-Ti complex, FeTi[N( o-(NCH2P( iPr)2)C6H4)3], abbreviated as TiL (1), and FeTiL (2), respectively. Herein, we describe the synthesis and characterization of the complete redox families of the monometallic Ti and Fe-Ti compounds. Cyclic voltammetry studies on FeTiL reveal both reduction and oxidation processes at -2.16 and -1.36 V (versus Fc/Fc+), respectively. Two isostructural redox members, [FeTiL]+ and [FeTiL]- (2ox and 2red, respectively) were synthesized and characterized, along with BrFeTiL (2-Br) and the monometallic [TiL]+ complex (1ox). The solid-state structures of the [FeTiL]+/0/- series feature short metal-metal bonds, ranging from 1.94-2.38 Å, which are all shorter than the sum of the Ti and Fe single-bond metallic radii (cf. 2.49 Å). To elucidate the bonding and electronic structures, the complexes were characterized with a host of spectroscopic methods, including NMR, EPR, and 57Fe Mössbauer, as well as Ti and Fe K-edge X-ray absorption spectroscopy (XAS). These studies, along with hybrid density functional theory (DFT) and time-dependent DFT calculations, suggest that the redox processes in the isostructural [FeTiL]+,0,- series are primarily Fe-based and that the polarized Fe-Ti π-bonds play a role in delocalizing some of the additional electron density from Fe to Ti (net 13%).

| S-EPMC6727590 | biostudies-literature

Unsymmetrical bimetallic complexes with M(II)-(?-OH)-M(III) cores (M(II)M(III) = Fe(II)Fe(III), Mn(II)Fe(III), Mn(II)Mn(III)): structural, magnetic, and redox properties.

Project description:Heterobimetallic cores are important units within the active sites of metalloproteins but are often difficult to duplicate in synthetic systems. We have developed a synthetic approach for the preparation of a complex with a Mn(II)-(?-OH)-Fe(III) core, in which the metal centers have different coordination environments. Structural and physical data support the assignment of this complex as a heterobimetallic system. A comparison with analogous homobimetallic complexes, Mn(II)-(?-OH)-Mn(III) and Fe(II)-(?-OH)-Fe(III) cores, further supports this assignment.

| S-EPMC3826960 | biostudies-other

Transition metal trifluoroacetates (M?=?Fe, Co, Mn) as precursors for uniform colloidal metal difluoride and phosphide nanoparticles.

Project description:We report a simple one-pot synthesis of uniform transition metal difluoride MF2 (M?=?Fe, Mn, Co) nanorods based on transition metal trifluoroacetates (TMTFAs) as single-source precursors. The synthesis of metal fluorides is based on the thermolysis of TMTFAs at 250-320?°C in trioctylphosphine/trioctylphosphine oxide solvent mixtures. The FeF2 nanorods were converted into FeF3 nanorods by reaction with gaseous fluorine. The TMTFA precursors are also found to be suitable for the synthesis of colloidal transition metal phosphides. Specifically, we report that the thermolysis of a cobalt trifluoroacetate complex in trioctylphosphine as both the solvent and the phosphorus source can yield 20 nm long cobalt phosphide nanorods or, 3 nm large cobalt phosphide nanoparticles. We also assess electrochemical lithiation/de-lithiation of the obtained FeF2 and FeF3 nanomaterials.

| S-EPMC6488600 | biostudies-literature

Oxoiron(IV) complexes as synthons for the assembly of heterobimetallic centers such as the Fe/Mn active site of Class Ic ribonucleotide reductases.

Project description:Nonheme oxoiron(IV) complexes can serve as synthons for generating heterobimetallic oxo-bridged dimetal complexes by reaction with divalent metal complexes. The formation of FeIII-O-CrIII and FeIII-O-MnIII complexes is described herein. The latter complexes may serve as models for the FeIII-X-MnIII active sites of an emerging class of Fe/Mn enzymes represented by the Class 1c ribonucleotide reductase from Chlamydia trachomatis and the R2-like ligand-binding oxidase (R2lox) found in Mycobacterium tuberculosis. These synthetic complexes have been characterized by UV-Vis, resonance Raman, and X-ray absorption spectroscopy, as well as electrospray mass spectrometry. The FeIII-O-CrIII complexes exhibit a three-band UV-Vis pattern that differs from the simpler features associated with FeIII-O-FeIII complexes. The positions of these features are modulated by the nature of the supporting polydentate ligand on the iron center, and their bands intensify dramatically in two examples upon the binding of an axial cyanate or thiocyanate ligand trans to the oxo bridge. In contrast, the FeIII-O-MnIII complexes resemble FeIII-O-FeIII complexes more closely. Resonance Raman characterization of the FeIII-O-MIII complexes reveals an 18O-sensitive vibration in the range of 760-890 cm-1. This feature has been assigned to the asymmetric FeIII-O-MIII stretching mode and correlates reasonably with the Fe-O bond distance determined by EXAFS analysis. The likely binding of an acetate as a bridging ligand to the FeIII-O-MnIII complex 12 lays the foundation for further efforts to model the heterobimetallic active sites of Fe/Mn enzymes.

| S-EPMC5756673 | biostudies-literature

Industrially Produced Fe- and Mn-Based Perovskites: Effect of Synthesis on Reactivity in Three-Way Catalysis: Part 1.

Project description:La0.6Ca0.2Fe0.8Cu0.2O3, undoped (LF) and Ca, Cu-doped (LCFC), powders, obtained by different industrial procedures, are compared to evaluate reproducibility and scale-up in different industrial synthetic approaches: flame spray pyrolysis (FSP) and coprecipitation (COP). Also the effects of varying composition (doping) and FSP process variability are considered as comparative studies on morphological, crystallographic, redox and compositional properties, and functional activity. A model reaction (CO + NO) and reactions with an automotive exhaust mixture were carried out. Unexpected results on the effectiveness of doping for catalytic activity emerged. Samples with the same compositions proved to be significantly affected by the synthesis, with variability within the same process. The activity of LCFC COP is comparable to the FSP analogue, at stoichiometric conditions, notwithstanding differences highlighted by characterization. In an oxygen-deficient mixture, LCFC-COP yields higher NO reduction and CO oxidation activity than LCFC-FSP. The absence of Ca in the lattice was unexpectedly beneficial. The doping effectiveness must be carefully checked for large-scale production.

| S-EPMC8482407 | biostudies-literature

Industrially Produced Fe- and Mn-Based Perovskites: Effect of Synthesis on Reactivity in Three-Way Catalysis: Part 2.

Project description:Mn-based perovskites obtained by two different industrial procedures [flame spray pyrolysis (FSP) and co-precipitation (COP)] have been extensively compared in terms of chemical, structural, and morphological properties with the aim of evaluating how the upscale of complex catalysts can affect the functionality. The transition between laboratory and production scale is, in fact, usually not straightforward. The catalytic activity was tested focusing on reactions of relevance in the abatement of pollutants. In particular, CO-assisted NO reduction (which could be also considered as a model reaction) and reactions with a synthetic automotive exhaust mixture, including 10% steam and oxygen, were carried out. The development of three-way catalysts is still a relevant question: noble metal-free, efficient catalysts are even more necessary in hybrid vehicles. For this purpose, the catalytic activity of the samples has been correlated with the characterization results and thus with the peculiar aspects of the production method. Relevant differences have been observed between COP and FSP catalysts, in terms of the specific surface area, surface composition, and presence of surface-active sites. Also, the different efficiencies of inserting dopants in the perovskite unit cell and thus in reducibility and ion mobility are relevant. Despite having the same composition and crystalline structure, the catalytic activity and the effect of pre-treatments are observed to depend on the production procedure.

| S-EPMC8482402 | biostudies-literature

Root shotgun proteomics from Fe- and Mn-deficient and Mn-toxic tomato plants

Project description:The aim of this work was to study the effects of Fe and Mn deficiencies and Mn toxicity on the protein profile of the root of tomato (Solanum lycopersicum), with the aim of elucidating plant response mechanisms to these nutritional stresses. Tomato was chosen as a model plant because the tomato genome has been published. The high-throughput shotgun analysis has permitted to identify and quantitate a large number of low abundance proteins in the tomato root. Protein identification was carried out using the Mascot search engine and the non-redundant databases NCBInr and ITAG v2.3.

2018-08-06 | PXD008326 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data