A5056974735- Sulfur Compounds in Biology
- Metalloenzymes and iron-sulfur proteins
- Folate and B Vitamins Research
- Redox biology and oxidative stress
- Heme Oxygenase-1 and Carbon Monoxide
- Trace Elements in Health
- Metabolism and Genetic Disorders
- Alcohol Consumption and Health Effects
- Adenosine and Purinergic Signaling
- DNA Repair Mechanisms
- Eicosanoids and Hypertension Pharmacology
- Nitric Oxide and Endothelin Effects
- Cancer therapeutics and mechanisms
- Metal-Catalyzed Oxygenation Mechanisms
- Amino Acid Enzymes and Metabolism
- ATP Synthase and ATPases Research
- Machine Learning in Bioinformatics
- Cancer-related gene regulation
- Biochemical and Molecular Research
- Fractal and DNA sequence analysis
- Iron Metabolism and Disorders
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Tea Polyphenols and Effects
- Alcoholism and Thiamine Deficiency
University of Michigan
2017-2021
Michigan Medicine
2021
Louisiana State University
2010-2020
Louisiana State University Agricultural Center
2015
The human mitochondrial outer membrane protein mitoNEET is a novel target of the type II diabetes drug pioglitazone. C-terminal cytosolic domain hosts redox-active [2Fe-2S] cluster via an unusual ligand arrangement three cysteine residues and one histidine residue. Here we report that clusters are fully reduced when expressed in Escherichia coli cells. In vitro studies show purified can be partially by monothiols such as glutathione, l-cysteine or N-acetyl-l-cysteine dithiothreitol E....
Summary Among the iron‐sulphur cluster assembly proteins encoded by gene iscSUA ‐ hscBA fdx in E scherichia coli , IscA has a unique and strong iron binding activity can provide for vitro . Deletion of its paralogue SufA results an mutant that fails to assemble [4 F e‐4 S ] clusters under aerobic conditions, suggesting crucial role biogenesis. Here we report among proteins, also specific Cu ( I ) vivo The centre is stable resistant oxidation conditions. Mutation conserved cysteine residues...
Buildup of hydrogen sulfide (H2S), which functions as a signaling molecule but is toxic at high concentrations, averted by its efficient oxidation the mitochondrial pathway. The first step in this pathway catalyzed flavoprotein, quinone oxidoreductase (SQR), converts H2S to persulfide and transfers electrons coenzyme Q via flavin cofactor. All previous studies on human SQR have used detergent-solubilized protein. Here, we embedded nanodiscs (ndSQR) studied highly homogenous preparations...
The dual roles of H2S as an endogenously synthesized respiratory substrate and a toxin raise questions to how it is cleared when the electron transport chain inhibited. Sulfide quinone oxidoreductase (SQOR) catalyzes first step in mitochondrial oxidation pathway, using CoQ acceptor, connects at level complex III. We have discovered that high concentrations, which are known inhibit IV, new redox cycle established between SQOR II, operating reverse. Under these conditions, purine nucleotide...
Hydrogen sulfide, a signaling molecule formed mainly from cysteine, is catabolized by sulfide:quinone oxidoreductase (gene SQOR). Toxic hydrogen sulfide exposure inhibits complex IV. We describe children of two families with pathogenic variants in SQOR. Exome sequencing identified variants; SQOR enzyme activity was measured spectrophotometrically, protein levels evaluated western blotting, and mitochondrial function assayed. In family A, following brief illness, 4-year-old girl presented...
Hydrogen sulfide is synthesized by enzymes involved in sulfur metabolism and oxidized via a dedicated mitochondrial pathway that intersects with the electron transport chain at level of complex III. Studies H2S are challenging since it volatile also reacts thiols culture medium, forming sulfane species. The half-life exogenously added to cultured cells unknown. In this study, we first examined human colonic epithelial cells. plate cultures, disappeared t1/2 3 4 min 37 °C small fraction being...
IscA is a key member of the iron-sulfur cluster assembly machinery in prokaryotic and eukaryotic organisms; however, physiological function still remains elusive. In present paper we report vivo evidence demonstrating iron-binding activity Escherichia coli cells. Supplement exogenous iron (1 μM) M9 minimal medium sufficient to maximize binding expressed E. cells under aerobic growth conditions. contrast, IscU, an scaffold protein, or CyaY, bacterial frataxin homologue, fails bind any same...
Iron-sulphur cluster biogenesis requires coordinated delivery of iron and sulphur to scaffold proteins, followed by transfer the assembled clusters from proteins target proteins. This complex process is accomplished a group dedicated iron-sulphur assembly that are conserved bacteria humans. While in provided L-cysteine via cysteine desulfurase, donor(s) for remains largely elusive. Here we report among primary IscA has unique strong binding activity mononuclear vitro vivo. Furthermore,...
The mitochondrial sulfide oxidation pathway prevents the toxic accumulation of hydrogen (H2S), a signaling molecule that is maintained at low steady-state concentrations. Sulfide quinone oxidoreductase (SQR), an inner membrane-anchored protein, catalyzes first and committing step in this pathway, oxidizing H2S to persulfide. catalytic cycle comprises addition active site cysteine disulfide SQR followed by sulfur transfer small acceptor, while pair electrons moves from sulfide, FAD, coenzyme...
Sulfide quinone oxidoreductase (SQOR) catalyzes the first step in sulfide clearance, coupling H2S oxidation to coenzyme Q reduction. Recent structures of human SQOR revealed a sulfur atom bridging active site cysteines trisulfide configuration. Here, we assessed importance this cofactor using kinetic, crystallographic, and computational modeling approaches. Cyanolysis proceeds via formation an intense charge transfer complex that subsequently decays eliminate thiocyanate. We captured...
Human telomere length regulator Rtel1 is a superfamily II DNA helicase and essential for maintaining proper of telomeres in chromosomes. Here we report that the N-terminal domain human (RtelN) expressed Escherichia coli cells produces protein contains redox active iron-sulfur cluster with midpoint potential −248 ± 10 mV (pH 8.0). The RtelN sensitive to hydrogen peroxide nitric oxide, indicating reactive oxygen/nitrogen species may modulate activity via modification its cluster. Purified...