Sulfur and Selenium: The Role of Oxidation State in Protein Structure and Function

Jacob, Claus; Giles, Gregory I.; Giles, Niroshini M.; Sies, Helmut

doi:10.1002/anie.200300573

Cited by 711 publications

(386 citation statements)

References 129 publications

(148 reference statements)

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“…Figure 3 shows the spectra of selected organic reference compounds, where one can notice that the position of the white line is similar for all compounds (except the second peak of the oxy-myoglobin, that comes from sulphate ligand). The results, presented in Table I, are consistent with the literature [9][10][11][12]. As should be noticed, there is a difference between formal and apparent oxidation state, received from XANES measurements, for example the apparent oxidation states of sulphur in thiosulphates, obtained from XANES data, are −1 and +5, while the formal ones are −2 and +6.…”

Section: Determination Of Oxidation States Of Sulphursupporting

confidence: 89%

Determination of Changes in Sulphur Oxidation States in Prostate Cancer Cells

et al. 2012

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Prostate cancer cell lines along with selected organic and inorganic compounds used as references were studied with sulphur K-edge X-ray absorption near edge structure spectroscopy. The experiment was performed at the SUL-X beamline of the synchrotron radiation source ANKA, Karlsruhe (Germany). The sulphur was chosen for the studies because it is an essential biological element and out of many relevant factors, it is believed that it can take an important part in cancer transformations. The main goal was to determine which sulphur forms occur in prostate cancer cells and to compare these results with the ones obtained for non-cancerous cells. Therefore oxidation state of this element was analysed with S K-edge X-ray absorption near edge structure spectroscopy. The analysis of K-edge structure was done in order to investigate also the chemical structure of the elements neighbouring the central atom. The preliminary results from sulphur X-ray absorption near edge structure in prostate cancer cell line PC-3 and prostatic epithelial cell line PZ-HPV-7 (which was used as a control) show that there are various oxidation states of sulphur occurring in cells. The set of reference compounds with various sulphur oxidation states was used to establish the relation between the energy of the white line maximum and the oxidation state of sulphur. The equation of linear fit was used to compute the unknown oxidation state. In order to obtain a more detailed information the method of deconvolution of X-ray absorption near edge structure spectra was used. Experimental spectra were fitted with two Gaussian peaks and one arctangent step function. Fitting procedure was performed in Athena code and the deconvolution was used to assign the fraction of each sulphur form. The next step was to compare the results calculated for cancerous and non-cancerous cells. In this work, the first results of these studies are presented.

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Section: Determination Of Oxidation States Of Sulphursupporting

confidence: 89%

Determination of Changes in Sulphur Oxidation States in Prostate Cancer Cells

et al. 2012

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“…In fact, 5 of the cysteines are predicted to be surface-exposed. Sulfur in cysteine can adopt several redox states, and Cys is therefore involved in a number of functions and it is a common site for posttranslational modifications 31 . In the case of mouse SR, Mustafa et al 27 have shown that modification at C113 can prevent ATP binding and activation.…”

Section: Thermal Stability Of C217s K221e and S84g/p111l Hsrmentioning

confidence: 99%

Random mutagenesis of human serine racemase reveals residues important for the enzymatic activity

Hoffman

Jirásková

Zvelebil

et al. 2010

Collect. Czech. Chem. Commun.

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Human serine racemase (hSR) is a cytosolic pyridoxal-5′-phosphate dependent enzyme responsible for production of D-serine in the central nervous system. D-Serine acts as an endogenous coagonist of N-methyl-D-aspartate receptor ion channels. Increased levels of D-serine have been linked to amyotrophic lateral sclerosis and Alzheimer's disease, indicating that SR inhibitors might be useful tools for investigation or treatment of neurodegenerative diseases. However, despite hSR's promise as a therapeutic target, relatively few specific inhibitors have been identified, which is due in part to the lack of a three-dimensional structure of the enzyme. Here, we present a strategy for the generation and screening of random hSR mutants. From a library of randomly mutated hSR variants, twenty-seven soluble mutants were selected, expressed, and evaluated for enzymatic activity. Taking three carefully characterized mutants as an example, we show how this strategy can be used to pinpoint structurally and functionally important residues. In particular, we identify S84 and P111 as residues crucial for hSR activity and C217 and K221 as residues important for binding of the Mg 2+ cofactor as well as for overall stability of the enzyme. Keywords: D-Serine; Serine racemase; Error-prone PCR; Random mutagenesis; ThermoFluor assay; Enzymes; Racemases; Enzyme engineering; In vitro evolution.Eukaryotic serine racemase (SR; EC 5.1.1.18) is a cytosolic pyridoxal-5′-phosphate (PLP) dependent enzyme responsible for the production of D-serine from L-serine and vice versa. In the mammalian central nervous system (CNS), D-serine acts as an endogenous coagonist of N-methyl-D-aspartate (NMDA) receptors, which are involved in glutamate-mediated excitatory neurotrans-

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“…5 The thiol and thioether groups are part of amino acids and their oxidation by metal ions has been studied for decades because of their important role in both the structure and function of proteins. 6 Oxidatively modified proteins accumulate during aging, oxidative stress and in age-related diseases, and some of them were found in liver, heart, skeletal muscle, kidney, and in regions of the brain. 5 L-Cysteine, L-methionine and the tripeptide glutathione (GSH, γ-glu-cys-gly) contain at least three potential donor groups, viz.…”

Section: Introductionmentioning

confidence: 99%

Substitution versus redox reactions of gold(iii) complexes with l-cysteine, l-methionine and glutathione

et al. 2014

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The influence of tridentate, nitrogen donor ligands, on the stability of gold(III) complexes under physiological conditions was investigated. The interaction of [Au(terpy)Cl] 2+ (terpy = 2,2':6'2'' terpyridine), [Au(bpma)Cl] 2+ (bpma = bis(pyridyl-methyl)amine), [Au(dien)Cl] 2+ (dien = diethylenetriamine) and [AuCl 4 ] − with the biologically relevant thiols, L-cysteine (L-Cys) and glutathione (GSH), and thioether, L-methionine (L-Met), was studied using UV-Vis spectroscopy, cyclic voltammetry, 1 H NMR spectroscopy and ESI-MS. In this study, the rate constants for substitution reactions between monofunctional gold(III) complexes and sulfur donor ligands in aqueous solution were determined at different initial concentrations of reactants, chloride ions, pH and constant ionic strength. The obtained second-order rate constants for the reaction with L-methionine in the absence of added chloride at pH 2.5 and 25°C follow the sequence (7.5 ± 0.4) × 10 3 > (4.5 ± 0.1) × 10 2 > 88.3 ± 0.8 M −1 s −1 for the terpy, bpma and dien complexes, respectively, demonstrating that the substitution step could be detected prior to the reduction step. This behavior was expected due to the influence of a decreasing π-donor ability of the chelate ligands, which slows down the substitution reactions along the series of complexes studied. In order to throw more light on the mechanism of biological activity of gold(III) compounds, such a systematic study was performed for all the mentioned thiols and thioether.

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Sulfur and Selenium: The Role of Oxidation State in Protein Structure and Function

Cited by 711 publications

References 129 publications

Determination of Changes in Sulphur Oxidation States in Prostate Cancer Cells

Determination of Changes in Sulphur Oxidation States in Prostate Cancer Cells

Random mutagenesis of human serine racemase reveals residues important for the enzymatic activity

Substitution versus redox reactions of gold(iii) complexes with l-cysteine, l-methionine and glutathione

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