Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion

Nature Genetics, Journal Year: 2007, Volume and Issue: 39(6), P. 776 - 780

Published: May 7, 2007

Language: Английский

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Current progress of siRNA/shRNA therapeutics in clinical trials

Biotechnology Journal, Journal Year: 2011, Volume and Issue: 6(9), P. 1130 - 1146

Published: July 11, 2011

Abstract Through a mechanism known as RNA interference (RNAi), small interfering (siRNA) molecules can target complementary mRNA strands for degradation, thus specifically inhibiting gene expression. The ability of siRNAs to inhibit expression offers that be exploited novel therapeutics. Indeed, over the past decade, at least 21 siRNA therapeutics have been developed more than dozen diseases, including various cancers, viruses, and genetic disorders. Like other biological drugs, RNAi‐based often require delivery vehicle transport them targeted cells. Thus, clinical advancement numerous drugs has relied on development carriers, biodegradable nanoparticles, lipids, bacteria, attenuated viruses. Most therapies permit systemic drug, while others use ex vivo by autologous cell therapy. Advancements in bioengineering nanotechnology led improved control release some Likewise, progress molecular biology allowed design molecules. Here, we provide an overview trials, their progress, challenges they encountered, future hold treatment human diseases.

Language: Английский

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Dioxygen Activation by Nonheme Diiron Enzymes: Diverse Dioxygen Adducts, High-Valent Intermediates, and Related Model Complexes

Chemical Reviews, Journal Year: 2018, Volume and Issue: 118(5), P. 2554 - 2592

Published: Feb. 5, 2018

A growing subset of metalloenzymes activates dioxygen with nonheme diiron active sites to effect substrate oxidations that range from the hydroxylation methane and desaturation fatty acids deformylation aldehydes produce alkanes six-electron oxidation aminoarenes nitroarenes in biosynthesis antibiotics. common feature their reaction mechanisms is formation O2 adducts evolve into more reactive derivatives such as diiron(II,III)-superoxo, diiron(III)-peroxo, diiron(III,IV)-oxo, diiron(IV)-oxo species, which carry out particular tasks. In this review, we survey various enzymes belonging unique by carried out. We examine nature intermediates, revealed X-ray crystallography application spectroscopic methods associated reactivity. also discuss structural electronic properties model complexes have been found mimic salient aspects these enzyme sites. Much has learned past 25 years, but key questions remain be answered.

Language: Английский

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Coupled Ferredoxin and Crotonyl Coenzyme A (CoA) Reduction with NADH Catalyzed by the Butyryl-CoA Dehydrogenase/Etf Complex from Clostridium kluyveri

Journal of Bacteriology, Journal Year: 2007, Volume and Issue: 190(3), P. 843 - 850

Published: Nov. 10, 2007

Cell extracts of butyrate-forming clostridia have been shown to catalyze acetyl-coenzyme A (acetyl-CoA)- and ferredoxin-dependent formation H2 from NADH. It has proposed that these bacteria contain an NADH:ferredoxin oxidoreductase which is allosterically regulated by acetyl-CoA. We report here ferredoxin reduction with NADH in cell Clostridium kluyveri catalyzed the butyryl-CoA dehydrogenase/Etf complex acetyl-CoA dependence previously observed due fact via crotonyl-CoA butyryl-CoA. The cytoplasmic dehydrogenase was purified couple endergonic (E0' = -410 mV) -320 exergonic -10 stoichiometry fully coupled reaction extrapolated be as follows: 2 + 1 oxidized NAD+ reduced two electrons implications this finding for energy metabolism anaerobes are discussed accompanying paper.

Language: Английский

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The Biochemistry of Methane Oxidation

Annual Review of Biochemistry, Journal Year: 2007, Volume and Issue: 76(1), P. 223 - 241

Published: Feb. 9, 2007

Methanotrophic bacteria oxidize methane to methanol in the first step of their metabolic pathway. Two forms monooxygenase (MMO) enzymes catalyze this reaction: soluble MMO (sMMO) and membrane-bound or particulate (pMMO). pMMO is expressed when copper available, its active site believed contain copper. Whereas sMMO well characterized, most aspects biochemistry remain unknown somewhat controversial. This review emphasizes advances past two three years related uptake copper-dependent regulation methanotrophs. The metal centers have been characterized spectroscopically, crystal structure has determined. Significant effort devoted improving vitro activity. Proteins involved additional copper-regulated proteins identified, Methylococcus capsulatus (Bath) genome sequenced. Finally, methanobactin (mb), a small chelator proposed facilitate uptake, characterized.

Language: Английский

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Thioredoxin and Thioredoxin Target Proteins: From Molecular Mechanisms to Functional Significance

Antioxidants and Redox Signaling, Journal Year: 2012, Volume and Issue: 18(10), P. 1165 - 1207

Published: May 21, 2012

The thioredoxin (Trx) system is one of the central antioxidant systems in mammalian cells, maintaining a reducing environment by catalyzing electron flux from nicotinamide adenine dinucleotide phosphate through Trx reductase to Trx, which reduces its target proteins using highly conserved thiol groups. While importance protecting cells detrimental effects reactive oxygen species clear, decades research this field revealed that there network redox-sensitive forming redox-dependent signaling pathways are crucial for fundamental cellular processes, including metabolism, proliferation, differentiation, migration, and apoptosis. participates interacting with different control their dynamic regulation structure function. In review, we focus on involved pathways. Specifically, Trx-dependent reductive enzymes participate classical redox reactions molecules discussed greater detail. latter extensively discussed, as ongoing unveils more details about complex networks Trx-sensitive such apoptosis signal-regulating kinase 1, protein, phosphatase tensin homolog, thus highlighting potential direct indirect impact interaction Trx. Overall, findings described here illustrate complexity Trx-dependent, cell. Our increasing understanding components mechanisms these could lead identification new targets treatment diseases, cancer diabetes. Antioxid. Redox Signal. 18, 1165–1207.

Language: Английский

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Ribonucleotide reductase and cancer: biological mechanisms and targeted therapies

Oncogene, Journal Year: 2014, Volume and Issue: 34(16), P. 2011 - 2021

Published: June 9, 2014

Language: Английский

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Cyclin F-Mediated Degradation of Ribonucleotide Reductase M2 Controls Genome Integrity and DNA Repair

Cell, Journal Year: 2012, Volume and Issue: 149(5), P. 1023 - 1034

Published: May 1, 2012

Language: Английский

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The cysteine proteome

Free Radical Biology and Medicine, Journal Year: 2015, Volume and Issue: 84, P. 227 - 245

Published: April 6, 2015

The cysteine (Cys) proteome is a major component of the adaptive interface between genome and exposome. thiol moiety Cys undergoes range biologic modifications enabling biological switching structure reactivity. These include sulfenylation disulfide formation, formation higher oxidation states, S-nitrosylation, persulfidation, metalation, other modifications. Extensive knowledge about these systems their compartmentalization now provides foundation to develop advanced integrative models regulation. In particular, detailed understanding redox signaling pathways sensing networks becoming available allow discrimination network structures. This research focuses attention on need for atlases biology models. Such will be especially useful studies linking imaging omics platforms, providing basis improved redox-based therapeutics. Thus, framework emerging place as complement quantitative in continuum connecting

Language: Английский

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The Ferritin-like superfamily: Evolution of the biological iron storeman from a rubrerythrin-like ancestor

Biochimica et Biophysica Acta (BBA) - General Subjects, Journal Year: 2010, Volume and Issue: 1800(8), P. 691 - 705

Published: May 28, 2010

Language: Английский

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