4.4 Article

Transiently Produced Hypochlorite Is Responsible for the Irreversible Inhibition of Chlorite Dismutase

Journal

BIOCHEMISTRY
Volume 53, Issue 19, Pages 3145-3157

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/bi500401k

Keywords

-

Funding

  1. Austrian Science Foundation, FWF [W1224, P25270, P22276]
  2. Austrian Science Fund (FWF) [W1224, P25270, P22276] Funding Source: Austrian Science Fund (FWF)
  3. Austrian Science Fund (FWF) [P 25270] Funding Source: researchfish

Ask authors/readers for more resources

Chlorite dismutases (Clds) are heme b-containing prokaryotic oxidoreductases that catalyze the reduction of chlorite to chloride with the concomitant release of molecular oxygen. Over time, they are irreversibly inactivated. To elucidate the mechanism of inactivation and investigate the role of the postulated intermediate hypochlorite, the pentameric chlorite dismutase of Candidatus Nitrospira defluvii (NdCld) and two variants (having the conserved distal arginine 173 exchanged with alanine and lysine) were recombinantly produced in Escherichia coli. Exchange of the distal arginine boosts the extent of irreversible inactivation. In the presence of the hypochlorite traps methionine, monochlorodimedone, and 2-[6-(4-aminophenoxy)-3-oxo-3H-xanthen-9-yl]benzoic acid, the extent of chlorite degradation and release of molecular oxygen is significantly increased, whereas heme bleaching and oxidative modifications of the protein are suppressed. Among other modifications, hypochlorite-mediated formation of chlorinated tyrosines is demonstrated by mass spectrometry. The data obtained were analyzed with respect to the proposed reaction mechanism for chlorite degradation and its dependence on pH. We discuss the role of distal Arg173 by keeping hypochlorite in the reaction sphere for O-O bond formation.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.4
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Biochemistry & Molecular Biology

Compound I Formation and Reactivity in Dimeric Chlorite Dismutase: Impact of pH and the Dynamics of the Catalytic Arginine

Daniel Schmidt, Nikolaus Falb, Ilenia Serra, Marzia Bellei, Vera Pfanzagl, Stefan Hofbauer, Sabine Van Doorslaer, Gianantonio Battistuzzi, Paul G. Furtmuller, Christian Obinger

BIOCHEMISTRY (2023)

Article Biochemistry & Molecular Biology

Active site architecture of coproporphyrin ferrochelatase with its physiological substrate coproporphyrin III: Propionate interactions and porphyrin core deformation

Andrea Dali, Thomas Gabler, Federico Sebastiani, Alina Destinger, Paul Georg Furtmueller, Vera Pfanzagl, Maurizio Becucci, Giulietta Smulevich, Stefan Hofbauer

Summary: Coproporphyrin ferrochelatases (CpfCs) are enzymes that catalyze the penultimate step in the coproporphyrin-dependent heme biosynthesis pathway. The discovery of the correct substrate for these ferrochelatases and the characterization of their binding mode provide valuable insights into the iron insertion process. This knowledge is essential for understanding the preconditions and mechanisms of iron insertion in CpfCs.

PROTEIN SCIENCE (2023)

Article Biochemistry & Molecular Biology

The Role of the Hydrogen Bond Network in Maintaining Heme Pocket Stability and Protein Function Specificity of C. diphtheriae Coproheme Decarboxylase

Federico Sebastiani, Chiara Baroni, Gaurav Patil, Andrea Dali, Maurizio Becucci, Stefan Hofbauer, Giulietta Smulevich

Summary: Monoderm bacteria accumulate heme b through the coproporphyrin-dependent biosynthesis pathway. The decarboxylation of propionate groups in coproheme by coproheme decarboxylase (ChdC) is a stepwise process. H-bond interactions in the pocket of ChdCs play a crucial role in stabilizing the active site and enzyme functionality, which were evaluated through characterization of mutants complexed with coproheme and heme b via spectroscopies.

BIOMOLECULES (2023)

Article Biochemistry & Molecular Biology

Common Reactivity and Properties of Heme Peroxidases: A DFT Study of Their Origin

Daniel R. Ramos, Paul G. Furtmueller, Christian Obinger, Angeles Pena-Gallego, Ignacio Perez-Juste, J. Arturo Santaballa

Summary: Electronic structure calculations using DFT were conducted to examine the influence of water molecules and protonation on the heme group of peroxidases in different redox and spin states. The study discusses shared geometries, spectroscopic properties, and thermodynamics of peroxidases. Computed Gibbs free energies suggest that the corresponding aquo complexes are not thermodynamically stable, supporting the five-coordinate Fe(III) center in native ferric peroxidases with a non-bonding water molecule. Protonation of the ferryl oxygen of compound II is found to be necessary and computed Gibbs free energies reveal pK(a) values of approximately 8.5-9.0 for compound II.

ANTIOXIDANTS (2023)

Article Chemistry, Analytical

Desorption of plasmid DNA from anion exchangers: Salt concentration at elution is independent of plasmid size and load

Jürgen Beck, Matthias Biechele, Christoph Repik, Petra Gruber, Paul G. Furtmueller, Rainer Hahn

Summary: This study systematically compared the elution behavior of plasmid DNA on three common anion exchange resins. It was found that plasmid DNA consistently elutes at a characteristic salt concentration in linear gradient elution, and elutes only above this concentration in isocratic elution. Structural analysis supported this explanation.

JOURNAL OF SEPARATION SCIENCE (2023)

Article Biochemistry & Molecular Biology

Reactivity of Coproheme Decarboxylase with Monovinyl, Monopropionate Deuteroheme

Gaurav Patil, Hanna Michlits, Paul G. Furtmueller, Stefan Hofbauer

Summary: Coproheme decarboxylases (ChdCs) are enzymes involved in the biosynthesis of heme. This study focuses on the second part of the decarboxylation reaction catalyzed by ChdCs, which has not been previously studied. The researchers optimized the production and purification of a intermediate compound called monovinyl, monopropionate deuteroheme (MMD), and used it to study the reaction mechanism. The results indicate that the second part of the reaction is similar to the first part, with slight differences in the active site architecture and H-bonding network.

BIOMOLECULES (2023)

Article Biochemistry & Molecular Biology

Amino Acid Residues Controlling Domain Interaction and Interdomain Electron Transfer in Cellobiose Dehydrogenase

Bettina Motycka, Florian Csarman, Melanie Rupp, Karoline Schnabel, Gabor Nagy, Kwankao Karnpakdee, Stefan Scheiblbrandner, Rupert Tscheliessnig, Chris Oostenbrink, Michal Hammel, Roland Ludwig

Summary: This study investigates the role of two crucial amino acids in cellobiose dehydrogenase (CDH) in the interaction between the dehydrogenase and cytochrome domains, as well as in the interdomain electron transfer. The results suggest that these two residues play an essential role in shaping the domain interaction and facilitating electron transfer.

CHEMBIOCHEM (2023)

Article Chemistry, Medicinal

Size Matters: Free-Energy Calculations of Amino Acid Adsorption over Pristine Graphene

Mateo Barria-Urenda, Alvaro Ruiz-Fernandez, Carlos Gonzalez, Chris Oostenbrink, Jose Antonio Garate

Summary: This study systematically investigated the adsorption process of amino acids onto graphene through free-energy calculations. A linear correlation was found between the free energy and the change in solvent accessible surface area, which could be used to predict the adsorption free energy of pentapeptides. Graphene oxidation resulted in a loss of favorability for amino acid adsorption.

JOURNAL OF CHEMICAL INFORMATION AND MODELING (2023)

Article Biochemistry & Molecular Biology

The role of the distal cavity in carbon monoxide stabilization in the coproheme decarboxylase enzyme from C. diphtheriae

Federico Sebastiani, Andrea Dali, Diego Javier Alonso de Armino, Lorenzo Campagni, Gaurav Patil, Maurizio Becucci, Stefan Hofbauer, Dario A. Estrin, Giulietta Smulevich

Summary: This study focuses on the carbon monoxide adducts of the wild-type and selected variants of the coproheme decarboxylase from actinobacterial Corynebacterium diphtheriae complexed with coproheme, monovinyl monopropionyl deuteroheme (MMD), and heme b. The results show that the wild-type coproheme-CO adduct is characterized by two CO conformers, hydrogen-bonded and weak polar interaction with the distal cavity. The absence of the H118 residue leads to the formation of non-H-bonded CO species. In addition, CO binding to reversed heme b and heme d is also investigated in this work.

JOURNAL OF INORGANIC BIOCHEMISTRY (2023)

Article Biochemistry & Molecular Biology

Iron insertion into coproporphyrin III-ferrochelatase complex: Evidence for an intermediate distorted catalytic species

Thomas Gabler, Andrea Dali, Federico Sebastiani, Paul Georg Furtmueller, Maurizio Becucci, Stefan Hofbauer, Giulietta Smulevich

Summary: Understanding the reaction mechanism of enzymes is challenging, but studying model substrates can provide valuable information. In this study, we investigated the mechanism of ferrous iron incorporation in a bacterial enzyme complex and discovered the role of hydrogen bond interactions in this process.

PROTEIN SCIENCE (2023)

Review Biochemistry & Molecular Biology

Structural aspects of enzymes involved in prokaryotic Gram-positive heme biosynthesis

Nikolaus Falb, Gaurav Patil, Paul G. Furtmueller, Thomas Gabler, Stefan Hofbauer

Summary: The coproporphyrin dependent heme biosynthesis pathway is predominantly used by Gram-positive bacteria. This pathway is of interest for basic research as it relates to medical biotechnology and the development of new antibiotic targets against Gram-positive superbugs. A review of the accumulated structural data on the enzymes involved in this pathway is provided, highlighting the need for further analysis and future research to gain a comprehensive understanding of prokaryotic heme biosynthesis.

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL (2023)

Article Biochemistry & Molecular Biology

Understanding the riddle of amine oxidase flavoenzyme reactivity on the stereoisomers of N-methyl-dopa and N-methyl-tyrosine

Oriol Gracia Carmona, Majd Lahham, Peter Poliak, Dominic Goj, Eva Friesser, Silvia Wallner, Peter Macheroux, Chris Oostenbrink

Summary: This study investigates the substrate specificity of the FsqB enzyme and discovers the role of tyrosine and aspartate residues in fixing the substrate close to the isoalloxazine ring of the cofactor. The combination of experimental and theoretical approaches helps solve the mystery behind the activity of FsqB enzyme.

JOURNAL OF MOLECULAR RECOGNITION (2023)

No Data Available