Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Harnessing the active site triad: merging hemilability, proton responsivity, and ligand-based redox-activity.

ABSTRACT: Metalloenzymes catalyze many important reactions by managing the proton and electron flux at the enzyme active site. The motifs utilized to facilitate these transformations include hemilabile, redox-active, and so called proton responsive sites. Given the importance of incorporating and understanding these motifs in the area of coordination chemistry and catalysis, we highlight recent milestones in the field. Work incorporating the triad of hemilability, redox-activity, and proton responsivity into single ligand scaffolds will be described.

SUBMITTER: Baumgardner DF

PROVIDER: S-EPMC7386000 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Harnessing the active site triad: merging hemilability, proton responsivity, and ligand-based redox-activity.

Baumgardner Douglas F DF Parks Wyatt E WE Gilbertson John D JD

Dalton transactions (Cambridge, England : 2003) 20200107 4

Metalloenzymes catalyze many important reactions by managing the proton and electron flux at the enzyme active site. The motifs utilized to facilitate these transformations include hemilabile, redox-active, and so called proton responsive sites. Given the importance of incorporating and understanding these motifs in the area of coordination chemistry and catalysis, we highlight recent milestones in the field. Work incorporating the triad of hemilability, redox-activity, and proton responsivity i ...[more]

PMID: 31907502

Similar Datasets

RedOx regulation of LRRK2 kinase activity by active site cysteines.

Project description:Mutations of the human leucine-rich repeat kinase 2 (LRRK2) have been associated with both, idiopathic and familial Parkinson's disease (PD). Most of these pathogenic mutations are located in the kinase domain (KD) or GTPase domain of LRRK2. In this study we describe a mechanism in which protein kinase activity can be modulated by reversible oxidation or reduction, involving a unique pair of adjacent cysteines, the "CC" motif. Among all human protein kinases, only LRRK2 contains this "CC" motif (C2024 and C2025) in the Activation Segment (AS) of the kinase domain. In an approach combining site-directed mutagenesis, biochemical analyses, cell-based assays, and Gaussian accelerated Molecular Dynamics (GaMD) simulations we could attribute a role for each of those cysteines. We employed reducing and oxidizing agents with potential clinical relevance to investigate effects on kinase activity and microtubule docking. We find that each cysteine gives a distinct contribution: the first cysteine, C2024, is essential for LRRK2 protein kinase activity, while the adjacent cysteine, C2025, contributes significantly to redox sensitivity. Implementing thiolates (R-S-) in GaMD simulations allowed us to analyse how each of the cysteines in the "CC" motif interacts with its surrounding residues depending on its oxidation state. From our studies we conclude that oxidizing agents can downregulate kinase activity of hyperactive LRRK2 PD mutations and may provide promising tools for therapeutic strategies.

| S-EPMC10991482 | biostudies-literature

Proton-coupled electron transfer in photosystem II: proton inventory of a redox active tyrosine.

Project description:Photosystem II (PSII) catalyzes the light driven oxidation of water and the reduction of plastoquinone. PSII is a multisubunit membrane protein; the D1 and D2 polypeptides form the heterodimeric core of the PSII complex. Water oxidation occurs at a manganese-containing oxygen evolving complex (OEC). PSII contains two redox active tyrosines, Y(Z) and Y(D), which form the neutral tyrosyl radicals, Y(z)(*) and Y(D)(*). Y(D) has been assigned as tyrosine 160 in the D2 polypeptide through isotopic labeling and site-directed mutagenesis. Whereas Y(D) is not directly involved in the oxidation of water, it has been implicated in the formation and stabilization of the OEC. PSII structures have shown Y(D) to be within hydrogen-bonding distance of histidine 189 in the D2 polypeptide. Spectroscopic studies have suggested that a proton is transferred between Y(D) and histidine 189 when Y(D) is oxidized and reduced. In our previous work, we used (2)H(2)O solvent exchange to demonstrate that the mechanism of Y(D) proton-coupled electron transfer (PCET) differs at high and low pH. In this article, we utilize the proton inventory technique to obtain more information concerning PCET mechanism at high pH. The hypercurvature of the proton inventory data provides evidence for the existence of multiple, proton-donation pathways to Y(D)(*). In addition, at least one of these pathways must involve the transfer of more than one proton.

| S-EPMC2846377 | biostudies-literature

Crystal structure, exogenous ligand binding, and redox properties of an engineered diiron active site in a bacterial hemerythrin.

Project description:A nonheme diiron active site in a 13 kDa hemerythrin-like domain of the bacterial chemotaxis protein DcrH-Hr contains an oxo bridge, two bridging carboxylate groups from Glu and Asp residues, and five terminally ligated His residues. We created a unique diiron coordination sphere containing five His and three Glu/Asp residues by replacing an Ile residue with Glu in DcrH-Hr. Direct coordination of the carboxylate group of E119 to Fe2 of the diiron site in the I119E variant was confirmed by X-ray crystallography. The substituted Glu is adjacent to an exogenous ligand-accessible tunnel. UV-vis absorption spectra indicate that the additional coordination of E119 inhibits the binding of the exogenous ligands azide and phenol to the diiron site. The extent of azide binding to the diiron site increases at pH ≤ 6, which is ascribed to protonation of the carboxylate ligand of E119. The diferrous state (deoxy form) of the engineered diiron site with the extra Glu residue is found to react more slowly than wild type with O2 to yield the diferric state (met form). The additional coordination of E119 to the diiron site also slows the rate of reduction from the met form. All these processes were found to be pH-dependent, which can be attributed to protonation state and coordination status of the E119 carboxylate. These results demonstrate that modifications of the endogenous coordination sphere can produce significant changes in the ligand binding and redox properties in a prototypical nonheme diiron-carboxylate protein active site.

| S-EPMC3873334 | biostudies-literature

Rhenium(V)-oxo corrolazines: isolating redox-active ligand reactivity.

Project description:The synthesis of the first example of a third-row metallocorrolazine characterized by single crystal X-ray diffraction is reported. This Re(V)(O) porphyrinoid complex shows an exclusively ligand-based reactivity with strong acids and oxidizing agents. The one-electron oxidized π-radical-cation complex is capable of H-atom abstraction.

| S-EPMC4679572 | biostudies-literature

Iron(II) Complexes Featuring a Redox-Active Dihydrazonopyrrole Ligand.

Project description:Nature uses control of the secondary coordination sphere to facilitate an astounding variety of transformations. Similarly, synthetic chemists have found metal-ligand cooperativity to be a powerful strategy for designing complexes that can mediate challenging reactivity. In particular, this strategy has been used to facilitate two electron reactions with first row transition metals that more typically engage in one electron redox processes. While NNN pincer ligands feature prominently in this area, examples which can potentially engage in both proton and electron transfer are less common. Dihydrazonopyrrole (DHP) ligands have been isolated in a variety of redox and protonation states when complexed to Ni. However, the redox-state of this ligand scaffold is less obvious when complexed to metal centers with more accessible redox couples. Here, we synthesize a new series of Fe-DHP complexes in two distinct oxidation states. Detailed characterization supports that the redox-chemistry in this set is still primarily ligand based. Finally, these complexes exist as 5-coordinate species with an open coordination site offering the possibility of enhanced reactivity.

| S-EPMC9435867 | biostudies-literature

Ligand field-actuated redox-activity of acetylacetonate.

Project description:The quest for simple ligands that enable multi-electron metal-ligand redox chemistry is driven by a desire to replace noble metals in catalysis and to discover novel chemical reactivity. The vast majority of simple ligand systems display electrochemical potentials impractical for catalytic cycles, illustrating the importance of creating new strategies towards energetically aligned ligand frontier and transition metal d orbitals. We herein demonstrate the ability to chemically control the redox-activity of the ubiquitous acetylacetonate (acac) ligand. By employing the ligand field of high-spin Cr(ii) as a switch, we were able to chemically tailor the occurrence of metal-ligand redox events via simple coordination or decoordination of the labile auxiliary ligands. The mechanism of ligand field actuation can be viewed as a destabilization of the d z 2 orbital relative to the π* LUMO of acac, which proffers a generalizable strategy to synthetically engineer redox-activity with seemingly redox-inactive ligands.

| S-EPMC8163028 | biostudies-literature

Merging bound states in the continuum by harnessing higher-order topological charges.

Project description:Bound states in the continuum (BICs) can confine light with a theoretically infinite Q factor. However, in practical on-chip resonators, scattering loss caused by inevitable fabrication imperfection leads to finite Q factors due to the coupling of BICs with nearby radiative states. Merging multiple BICs can improve the robustness of BICs against fabrication imperfection by improving the Q factors of nearby states over a broad wavevector range. To date, the studies of merging BICs have been limited to fundamental BICs with topological charges ±1. Here we show the unique advantages of higher-order BICs (those with higher-order topological charges) in constructing merging BICs. Merging multiple BICs with a higher-order BIC can further improve the Q factors compared with those involving only fundamental BICs. In addition, higher-order BICs offer great flexibility in realizing steerable off-Γ merging BICs. A higher-order BIC at Γ can split into a few off-Γ fundamental BICs by reducing the system symmetry. The split BICs can then be tuned to merge with another BIC, e.g., an accidental BIC, at an off-Γ point. When the in-plane mirror symmetry is further broken, merging BICs become steerable in the reciprocal space. Merging BICs provide a paradigm to achieve robust ultrahigh-Q resonances, which are important in enhancing nonlinear and quantum effects and improving the performance of optoelectronic devices.

| S-EPMC9296527 | biostudies-literature

Tuning Redox Active Polyoxometalates for Efficient Electron-Coupled Proton-Buffer-Mediated Water Splitting.

Project description:We present strategies to tune the redox properties of polyoxometalate clusters to enhance the electron-coupled proton-buffer-mediated water splitting process, in which the evolution of hydrogen and oxygen can occur in different forms and is separated in time and space. By substituting the heteroatom template in the Keggin-type polyoxometalate cluster, H6 ZnW12 O40 , it is possible to double the number of electrons and protonation in the redox reactions (from two to four). This increase can be achieved with better matching of the energy levels as indicated by the redox potentials, compared to the ones of well-studied H3 PW12 O40 and H4 SiW12 O40 . This means that H6 ZnW12 O40 can act as a high-performance redox mediator in an electrolytic cell for the on-demand generation of hydrogen with a high decoupling efficiency of 95.5 % and an electrochemical energy efficiency of 83.3 %. Furthermore, the H6 ZnW12 O40 cluster also exhibits an excellent cycling behaviour and redox reversibility with almost 100 % H2 -mediated capacity retention during 200 cycles and a high coulombic efficiency >92 % each cycle at 30 mA cm-2 .

| S-EPMC6851869 | biostudies-literature

The Redox-Active Tyrosine Is Essential for Proton Pumping in Cytochrome c Oxidase.

Project description:Cellular respiration involves electron transport via a number of enzyme complexes to the terminal Cytochrome c oxidase (CcO), in which molecular oxygen is reduced to water. The free energy released in the reduction process is used to establish a transmembrane electrochemical gradient, via two processes, both corresponding to charge transport across the membrane in which the enzymes are embedded. First, the reduction chemistry occurring in the active site of CcO is electrogenic, which means that the electrons and protons are delivered from opposite sides of the membrane. Second, the exergonic chemistry is coupled to translocation of protons across the entire membrane, referred to as proton pumping. In the largest subfamily of the CcO enzymes, the A-family, one proton is pumped for every electron needed for the chemistry, making the energy conservation particularly efficient. In the present study, hybrid density functional calculations are performed on a model of the A-family CcOs. The calculations show that the redox-active tyrosine, conserved in all types of CcOs, plays an essential role for the energy conservation. Based on the calculations a reaction mechanism is suggested involving a tyrosyl radical (possibly mixed with tyrosinate character) in all reduction steps. The result is that the free energy released in each reduction step is large enough to allow proton pumping in all reduction steps without prohibitively high barriers when the gradient is present. Furthermore, the unprotonated tyrosine provides a mechanism for coupling the uptake of two protons per electron in every reduction step, i.e. for a secure proton pumping.

| S-EPMC8079940 | biostudies-literature

Redox-Active Guanidines in Proton-Coupled Electron-Transfer Reactions: Real Alternatives to Benzoquinones?

Project description:Guanidino-functionalized aromatics (GFAs) are readily available, stable organic redox-active compounds. In this work we apply one particular GFA compound, 1,2,4,5-tetrakis(tetramethylguanidino)benzene, in its oxidized form in a variety of oxidation/oxidative coupling reactions to demonstrate the scope of its proton-coupled electron transfer (PCET) reactivity. Addition of an excess of acid boosts its oxidation power, enabling the oxidative coupling of substrates with redox potentials of at least +0.77 V vs. Fc+ /Fc. The green recyclability by catalytic re-oxidation with dioxygen is also shown. Finally, a direct comparison indicates that GFAs are real alternatives to toxic halo- or cyano-substituted benzoquinones.

| S-EPMC7065378 | biostudies-literature

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