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Claus Jacob

Publications and source records attributed to Claus Jacob.

8 recordsLinked to original sources
PubMed2003

Sulfur and selenium: the role of oxidation state in protein structure and function.

Sulfur and selenium occur in proteins as constituents of the amino acids cysteine, methionine, selenocysteine, and selenomethionine. Recent research underscores that these amino acids are truly exceptional. Their redox activity under physiological conditions allows an amazing variety of posttranslational protein modifications, metal free redox pathways, and unusual chalcogen redox states that increasingly attract the attention of biological chemists. Unlike any other amino acid, the "redox chameleon" cysteine can participate in several distinct redox pathways, including exchange and radical reactions, as well as atom-, electron-, and hydride-transfer reactions. It occurs in various oxidation states in the human body, each of which exhibits distinctive chemical properties (e.g. redox activity, metal binding) and biological activity. The position of selenium in the periodic table between the metals and the nonmetals makes selenoproteins ideal catalysts for many biological redox transformations. It is therefore apparent that the chalcogen amino acids cysteine, methionine, selenocysteine, and selenomethionine exhibit a unique biological chemistry that is the source of exciting research opportunities.

Cysteine↗
PubMed2003

Redox catalysts as sensitisers towards oxidative stress.

The predominance of oxidative stress in many tumour cell environments provides a means to selectively target these cells via protein oxidation. The zinc fingers of transcription factors utilise cysteine thiols for structural zinc coordination. Redox control of DNA binding regulates transcription and therefore the overall rates of proliferation, apoptosis and necrosis in the carcinoma. We report here the adverse effects of glutathione peroxidase (GPx) mimics towards zinc finger motifs and PC12 cell survival. Nanomolar catalyst concentrations facilitated H2O2-induced oxidation of an Sp1 transcription factor fragment. In PC12 cells GPx catalysis triggered a significant increase in cell death, correlating with severity of oxidative stress. As a consequence, we conclude that GPx mimics are potential chemotherapeutic agents.

Animals↗
PubMed2003

Multiple roles of cysteine in biocatalysis.

In biology, sulfur frequently occurs in the form of cysteine, an amino acid that fulfills a wide range of different functions in proteins including disulfide formation, metal-binding, electron donation, hydrolysis, and redox-catalysis. The 'redox-chameleon' sulfur appears in several oxidation states in vitro, each of them exhibiting specific reactivity, redox-activity, and metal-binding properties. While cysteine-peptidases rely on reduced cysteine to catalyze hydrolytic reactions, many redox-enzymes use distinctively different cysteine redox-couples for exchange, electron, atom, and radical transfer reactions. Although cysteine and cystine can still be considered as the most abundant forms of cysteine in vivo, other modifications such as cysteine acids and sulfur-centered radicals are becoming increasingly important in biochemical research. As such, the biochemistry of sulfur remains a source of continuous investigation and excitement.

Catalysis↗
PubMed2003

Metal and redox modulation of cysteine protein function.

In biological systems, the amino acid cysteine combines catalytic activity with an extensive redox chemistry and unique metal binding properties. The interdependency of these three aspects of the thiol group permits the redox regulation of proteins and metal binding, metal control of redox activity, and ligand control of metal-based enzyme catalysis. Cysteine proteins are therefore able to act as "redox switches," to sense concentrations of oxidative stressors and unbound zinc ions in the cytosol, to provide a "storage facility" for excess metal ions, to control the activity of metalloproteins, and to take part in important regulatory and signaling pathways. The diversity of cysteine's multiple roles in vivo is equally as fascinating as it is promising for future biochemical and pharmacological research.

Catalysis↗
PubMed2003

Statement analysis in chemistry.

Close philosophical examination of chemical research reports ("statement analysis") can lead to clarification of ambiguities and resolution of logical confusions, and also lead to other useful conclusions.

Journal Article↗
PubMed2002

Reactive sulphur species: an in vitro investigation of the oxidation properties of disulphide S-oxides.

We have recently proposed that disulphide S-monoxides (thiosulphinates) and disulphide S-dioxides (thiosulphonates) are formed from their parent disulphides and 'reactive oxygen species' during oxidative stress. These 'reactive sulphur species' are themselves strong oxidizing agents that preferably attack the thiol functionality. We now show that under conditions where disulphides show little effect, disulphide S-oxides rapidly modify metallothionein, alcohol and glyceraldehyde 3-phosphate dehydrogenases and a zinc finger-protein fragment in vitro. The known antioxidants ascorbate, NADH, trolox and melatonin are unable to inhibit this oxidation pathway and only an excess of the cellular redox-buffer glutathione quenches the disulphide S-oxide activity. These results suggest that, under conditions of oxidative stress, despite the presence of high concentrations of antioxidants, reactive sulphur species formation may occur and inhibit the function of thiol-dependent proteins. Such a characterization of the disulphide S-oxide-oxidation pathway might also account for some previously observed anomalies in protein oxidation.

Antioxidants↗
PubMedDate not supplied

Reactive sulfur species: an emerging concept in oxidative stress.

The ingredients of oxidative stress include a variety of reactive species such as reactive oxygen and reactive nitrogen species (ROS, RNS). While sulfur is usually considered as part of cellular antioxidant systems there is mounting evidence that reactive sulfur species (RSS) with stressor properties similar to the ones found in ROS are formed under conditions of oxidative stress. Thiols as well as disulfides are easily oxidised to sulfur species with sulfur in higher oxidation states. Such agents include thiyl radicals, disulfides, sulfenic acids and disulfide-S-oxides. They rapidly oxidise and subsequently inhibit thiol-proteins and enzymes and can be considered as a separate class of oxidative stressors providing new antioxidant drug targets.

Animals↗