scholarly journals Theoretical Study on Redox Potential Control of Iron-Sulfur Cluster by Hydrogen Bonds: A Possibility of Redox Potential Programming

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6129
Author(s):  
Iori Era ◽  
Yasutaka Kitagawa ◽  
Natsumi Yasuda ◽  
Taigo Kamimura ◽  
Naoka Amamizu ◽  
...  
Keyword(s):  
Hydrogen Bonds ◽  
Redox Potential ◽  
Active Site ◽  
Density Functional ◽  
Redox Potentials ◽  
Iron Sulfur Cluster ◽  
Potential Control ◽  
Iron Sulfur ◽  
And Shifts ◽  
Reduced State

The effect of hydrogen bonds around the active site of Anabaena [2Fe-2S] ferredoxin (Fd) on a vertical ionization potential of the reduced state (IP(red)) is examined based on the density functional theory (DFT) calculations. The results indicate that a single hydrogen bond increases the relative stability of the reduced state, and shifts IP(red) to a reductive side by 0.31–0.33 eV, regardless of the attached sulfur atoms. In addition, the IP(red) value can be changed by the number of hydrogen bonds around the active site. The results also suggest that the redox potential of [2Fe-2S] Fd is controlled by the number of hydrogen bonds because IP(red) is considered to be a major factor in the redox potential. Furthermore, there is a possibility that the redox potentials of artificial iron-sulfur clusters can be finely controlled by the number of the hydrogen bonds attached to the sulfur atoms of the cluster.

Mössbauer Studies of the Iron−Sulfur Cluster-Free Hydrogenase:  The Electronic State of the Mononuclear Fe Active Site

2005 ◽  
Vol 127 (29) ◽  
pp. 10430-10435 ◽  
Author(s):  
Seigo Shima ◽  
Erica J. Lyon ◽  
Rudolf K. Thauer ◽  
Bernd Mienert ◽  
Eckhard Bill
Keyword(s):  
Electronic State ◽  
Active Site ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
Mössbauer Studies ◽  
Iron Sulfur

scholarly journals Bridging the experiment-calculation divide: machine learning corrections to redox potential calculations in implicit and explicit solvent models

2021 ◽  
Author(s):  
Eugen Hruska ◽  
Ariel Gale ◽  
Fang Liu
Keyword(s):  
Machine Learning ◽  
Redox Potential ◽  
Density Functional ◽  
Implicit Solvent ◽  
Systematic Bias ◽  
Redox Potentials ◽  
Solvent Models ◽  
Explicit Solvent ◽  
Solvent Model ◽  
Implicit And Explicit

Prediction of redox potentials is essential for catalysis and energy storage. Although density functional theory (DFT) calculations have enabled rapid redox potential predictions for numerous compounds, prominent errors persist compared to experimental measurements. In this work, we develop machine learning (ML) models to reduce the errors of redox potential calculations in both implicit and explicit solvent models. Training and testing of the ML correction models are based on the diverse ROP313 dataset with experimental redox potentials measured for organic and organometallic compounds in a variety of solvents. For the implicit solvent approach, our ML models can reduce both the systematic bias and the number of outliers. ML corrected redox potentials also demonstrate less sensitivity to DFT functional choice. For the explicit solvent approach, we significantly reduce the computational costs by embedding the microsolvated cluster in implicit bulk solvent, obtaining converged redox potential results with a smaller solvation shell. This combined implicit-explicit solvent model, together with GPU-accelerated quantum chemistry methods, enabled rapid generation of a large dataset of explicit-solvent-calculated redox potentials for 165 organic compounds, allowing detailed investigation of the error sources in explicit solvent redox potential calculations.

scholarly journals Effect of Sequences of the Active-Site Dipeptides of DsbA and DsbC on In Vivo Folding of Multidisulfide Proteins inEscherichia coli

2001 ◽  
Vol 183 (3) ◽  
pp. 980-988 ◽  
Author(s):  
Paul H. Bessette ◽  
Ji Qiu ◽  
James C. A. Bardwell ◽  
James R. Swartz ◽  
George Georgiou
Keyword(s):  
Redox Potential ◽  
Active Site ◽  
Active Sites ◽  
Multicopy Plasmid ◽  
Redox Potentials ◽  
Cxxc Motif ◽  
Wide Range ◽  
Significant Difference ◽  
Disulfide Isomerization

ABSTRACT We have examined the role of the active-site CXXC central dipeptides of DsbA and DsbC in disulfide bond formation and isomerization in the Escherichia coli periplasm. DsbA active-site mutants with a wide range of redox potentials were expressed either from the trc promoter on a multicopy plasmid or from the endogenous dsbA promoter by integration of the respective alleles into the bacterial chromosome. ThedsbA alleles gave significant differences in the yield of active murine urokinase, a protein containing 12 disulfides, including some that significantly enhanced urokinase expression over that allowed by wild-type DsbA. No direct correlation between the in vitro redox potential of dsbA variants and the urokinase yield was observed. These results suggest that the active-site CXXC motif of DsbA can play an important role in determining the folding of multidisulfide proteins, in a way that is independent from DsbA's redox potential. However, under aerobic conditions, there was no significant difference among the DsbA mutants with respect to phenotypes depending on the oxidation of proteins with few disulfide bonds. The effect of active-site mutations in the CXXC motif of DsbC on disulfide isomerization in vivo was also examined. A library of DsbC expression plasmids with the active-site dipeptide randomized was screened for mutants that have increased disulfide isomerization activity. A number of DsbC mutants that showed enhanced expression of a variant of human tissue plasminogen activator as well as mouse urokinase were obtained. These DsbC mutants overwhelmingly contained an aromatic residue at the C-terminal position of the dipeptide, whereas the N-terminal residue was more diverse. Collectively, these data indicate that the active sites of the soluble thiol- disulfide oxidoreductases can be modulated to enhance disulfide isomerization and protein folding in the bacterial periplasmic space.

Impact of the Iron–Sulfur Cluster Proximal to the Active Site on the Catalytic Function of an O2-Tolerant NAD+-Reducing [NiFe]-Hydrogenase

Biochemistry ◽  
2015 ◽  
Vol 54 (2) ◽  
pp. 389-403 ◽  
Author(s):  
Katja Karstens ◽  
Stefan Wahlefeld ◽  
Marius Horch ◽  
Miriam Grunzel ◽  
Lars Lauterbach ◽  
...  
Keyword(s):  
Active Site ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
Catalytic Function ◽  
Iron Sulfur

The importance of iron in the biosynthesis and assembly of [NiFe]-hydrogenases

2014 ◽  
Vol 5 (1) ◽  
pp. 55-70 ◽  
Author(s):  
Constanze Pinske ◽  
R. Gary Sawers
Keyword(s):  
Active Site ◽  
Large Subunit ◽  
Small Subunit ◽  
Transport Systems ◽  
Bacterial Cells ◽  
Carbamoyl Phosphate ◽  
Iron Sulfur Cluster ◽  
Iron Sulfur ◽  
Redox Active ◽  
Cofactor Biosynthesis

Abstract[NiFe]-hydrogenases (Hyd) are redox-active metalloenzymes that catalyze the reversible oxidation of molecular hydrogen to protons and electrons. These enzymes are frequently heterodimeric and have a unique bimetallic active site in their catalytic large subunit and possess a complement of iron sulfur (Fe-S) clusters for electron transfer in the small subunit. Depending on environmental and metabolic requirements, the Fe-S cluster relay shows considerable variation among the Hyd, even employing high potential [4Fe-3S] clusters for improved oxygen tolerance. The general iron sulfur cluster (Isc) machinery is required for small subunit maturation, possibly providing standard [4Fe-4S], which are then modified as required in situ. The [NiFe] cofactor in the active site also has an iron ion to which one CO and two CN- diatomic ligands are attached. Specific accessory proteins synthesize these ligands and insert the cofactor into the apo-hydrogenase large subunit. Carbamoyl phosphate is the precursor of the CN- ligands, and recent experimental evidence suggests that endogenously generated CO2 might be one precursor of CO. Recent advances also indicate how the machineries responsible for cofactor generation obtain iron. Several transport systems for iron into bacterial cells exist; however, in Escherichia coli, it is mainly the ferrous iron transporter Feo and the ferric-citrate siderphore system Fec that are involved in delivering the metal for Hyd biosynthesis. Genetic analyses have provided evidence for the existence of key checkpoints during cofactor biosynthesis and enzyme assembly that ensure correct spatiotemporal maturation of these modular oxidoreductases.

Solution NMR Structure of the Iron–Sulfur Cluster Assembly Protein U (IscU) with Zinc Bound at the Active Site

2004 ◽  
Vol 344 (2) ◽  
pp. 567-583 ◽  
Author(s):  
Theresa A. Ramelot ◽  
John R. Cort ◽  
Sharon Goldsmith-Fischman ◽  
Gregory J. Kornhaber ◽  
Rong Xiao ◽  
...  
Keyword(s):  
Active Site ◽  
Nmr Structure ◽  
Solution Nmr ◽  
Cluster Assembly ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
Iron Sulfur

scholarly journals Redox response of iron-sulfur glutaredoxin GRXS17 activates its holdase activity to protect plants from heat stress

2020 ◽  
Author(s):  
Laura Martins ◽  
Johannes Knuesting ◽  
Laetitia Bariat ◽  
Avilien Dard ◽  
Sven A. Freibert ◽  
...  
Keyword(s):  
Heat Stress ◽  
Active Site ◽  
Disulfide Bonds ◽  
Dependent Manner ◽  
Plant Tolerance ◽  
Iron Sulfur Cluster ◽  
Subsequent Formation ◽  
Iron Sulfur ◽  
Root Meristematic Cells ◽  
Living Organisms

ABSTRACTLiving organisms use a large panel of mechanisms to protect themselves from environmental stress. Particularly, heat stress induces misfolding and aggregation of proteins which are guarded by chaperone systems. Here, we examine the function the glutaredoxin GRXS17, a member of thiol reductases families in the model plant Arabidopsis thaliana. GRXS17 is a nucleocytosolic monothiol glutaredoxin consisting of an N-terminal thioredoxin (TRX)-domain and three CGFS-active site motif-containing GRX-domains that coordinate three iron-sulfur (Fe-S) clusters in a glutathione (GSH)-dependent manner. As a Fe-S cluster-charged holoenzyme, GRXS17 is likely involved in the maturation of cytosolic and nuclear Fe-S proteins. In addition to its role in cluster biogenesis, we showed that GRXS17 presents both foldase and redox-dependent holdase activities. Oxidative stress in combination with heat stress induces loss of its Fe-S clusters followed by subsequent formation of disulfide bonds between conserved active site cysteines in the corresponding TRX domains. This oxidation leads to a shift of GRXS17 to a high-MW complex and thus, activates its holdase activity. Moreover, we demonstrate that GRXS17 is specifically involved in plant tolerance to moderate high temperature and protects root meristematic cells from heat-induced cell death. Finally, we showed that upon heat stress, GRXS17 changes its client proteins, possibly to protect them from heat injuries. Therefore, we propose that the iron-sulfur cluster enzyme glutaredoxin GRXS17 is an essential guard to protect proteins against moderate heat stress, likely through a redox-dependent chaperone activity. All in all, we reveal the mechanism of an Fe-S cluster-dependent activity shift, turning the holoenzyme GRXS17 into a holdase that prevents damage caused by heat stress.

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