Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.2.13 (aldolase)
 3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Statistically significant charge clusters (basic, acidic, or of mixed charge) in tertiary protein structures are identified by new methods from a large representative collection of protein structures. About 10% of protein structures show at least one charge cluster, mostly of mixed type involving about equally anionic and cationic residues. Positive charge clusters are very rare. Negative (or histidine-acidic) charge clusters often coordinate calcium, or magnesium or zinc ions [e.g., thermolysin (PDB code: 3tln), mannose-binding protein (2msb), aminopeptidase (1amp)]. Mixed-charge clusters are prominent at interchain contacts where they stabilize quaternary protein formation [e.g., glutathione S-transferase (2gst), catalase (8act), and fructose-1,6-bisphosphate aldolase (1fba)]. They are also involved in protein-protein interaction and in substrate binding. For example, the mixed-charge cluster of aspartate carbamoyl-transferase (8atc) envelops the aspartate carbonyl substrate in a flexible manner (alternating tense and relaxed states) where charge associations can vary from weak to strong. Other proteins with charge clusters include the P450 cytochrome family (BM-3, Terp, Cam), several flavocytochromes, neuraminidase, hemagglutinin, the photosynthetic reaction center, and annexin. In each case in Table 2 we discuss the possible role of the charge clusters with respect to protein structure and function.
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PMID:Clusters of charged residues in protein three-dimensional structures. 871 Aug 74

This study uses microsomal membranes from rat testis tissue, including the cytochrome P450c17 (steroid 17 alpha-monooxygenase/17 alpha-hydroxyprogesterone aldolase, catalyzing the conversion of progesterone to androstenedione), to decipher the possible relation of NADPH-induced (no exogenous iron added) lipid peroxidation and cytochrome P450 inactivation and the protective effect of certain steroids. NADPH (300 microM) causes a 3.6-fold stimulation of malondialdehyde formation (thiobarbituric acid-reactive substances) and a 29% cytochrome P450c17 loss within 1 h at 37 degrees C, but has no effect on lipid peroxidation in the presence of the iron chelator desferrioxamine. Hydrogen peroxide has only marginal effects. The antioxidant efficiency of estradiol (IC50 = 13.9 microM) is higher than its cytochrome P450c17 protective efficiency (IC50 = 33.0 microM), whereas androstenedione does not inhibit lipid peroxidation but protects cytochrome P450c17 completely. The human choriogonadotropin-induced degradation of cytochrome P450c17 in incubated decapsulated testes can not be correlated with a stimulation of lipid peroxidation, and it is partially inhibited by estradiol but completely abolished by androstenedione. It is concluded (I) that NADPH stimulates iron-dependent generation of reactive oxygen species by the monooxygenase system even in the presence of certain P450 ligands in the physiological membrane environment, (II) that membrane lipid peroxidation may be suppressed by hydrophobic steroids acting as antioxidants such as estradiol, (III) that steroid ligands stabilize cytochrome P450c17 against inactivation in the presence of NADPH even if they do not act as substrates and do not possess antioxidant activity, and (IV) that the choriogonadotropin-induced down-regulation of cytochrome P450c17 is not due to accumulating steroids acting as "pseudosubstrates" as occasionally supposed.
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PMID:Novel connections between NADPH-induced lipid peroxidation and cytochrome P450 inactivation, and antioxidant and enzyme protective properties of estradiol in gonadal membranes. 925 24

Stable lysine adducts were formed in proteins following reaction with trichloroethylene (TCE) oxide, the major reactive compound generated by the metabolism of TCE. The order of formation of these adducts is N(6)-formyllysine > N(6)-(dichloroacetyl)lysine >> N(6)-glyoxyllysine, with the ratio being influenced by the particular protein. Protein lysine adducts were also analyzed following the enzymatic oxidation of TCE with several different cytochrome P450 (P450) enzyme systems. The ratio of formyl/dichloroacetyl lysine adducts was influenced by the enzyme system that was used. Chloral and TCE oxide formation was more extensive with rat liver microsomes isolated from phenobarbital-treated rats than with rat microsomes in which P450 2E1 was induced by treatment with isoniazid or in human P450 2E1 systems. Glutathione (GSH) and GSH transferase had inhibitory effects on the reaction of TCE oxide with albumin, with formylation being atteunated much more than the formation of dichloroacetyllysine. GSH is likely to react with the reactive acyl chloride intermediates formed from TCE oxide hydrolysis, instead of direct reaction with TCE oxide, as judged by the lack of an effect of GSH on the rate of decomposition of TCE oxide. Studies with the model enzymes aldolase and glucose-6-phosphate dehydrogenase, both known to have sensitive lysine groups, indicate that TCE oxide has effects similar to known acylating agents that form the same adducts; concentrations of TCE oxide (or the model acylating agents) in the low-millimolar range were needed for inhibition. The characterization of TCE-derived protein adducts can be used as a basis for consideration of the exposure and risk of TCE to humans. Human P450 2E1 was less likely to oxidize TCE to form TCE oxide and protein lysine adducts than rat P450 2B1, and the difference is rationalized in terms of the influence of the protein on chloride migration in an enzyme reaction intermediate.
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PMID:Acylation of protein lysines by trichloroethylene oxide. 1081 48

Workers are occupationally exposed to Pd and Pd-complexes during the refining process, in particular in Pt-refineries. The metal is increasingly used as component in fine jewellery, is commonly present in dental alloys, and is also employed in telecommunication systems.In view of the toxicity of Pd when absorbed and anticipating the possible entry of some of this material into man's environment from the use of automotive catalitic converters, the retention, tissue distribution, excretion and placental transfer of Pd were determined by several authors following different administration routes in animal experiments. Most investigations on Pd and the Pt group metals were performed with simple and complex salts (chlorides and water-soluble ammoniacal compounds of Pt, Ir, Os, Pd, Rh and Ru). The highest retention for Pd was obtained following intravenous dosing, and the lowest retention occured after oral administration. Following a single oral dose, almost all Pd is excreted in the faeces, whereas after i.v. injections, similar quantities are excreted in both urine and faeces. Tissues containing the highest concentrations were the kidneys, spleen and liver. Following i.v. dosing of pregnant rats, a small amount is found in the fetuses.Pd and its compounds are considered to have hepatotoxic and nephrotoxic effects, acting by way of the -SH groups on complex biosystems: proteins, enzymes, etc. Oral administration of PdCh2 has obvious effects on the hepatic mono-oxygenase system and causes notable decreases in hepatic content of cytochrome-P450. Pd++ salts have also metabolic effects on a lot of other enzymes by inhibiting the activity of prolyl-hydroxylase, creatine kinase, aldolase, succinic dehydrogenase, carbonic anhydrase and alkaline phosphatase. These studies suggest that Pd may interfere with energy metabolism, acidlbase and electrolyte eqUilibria. In addition, Pd significantly increases the hepatic Se content and has a strong interaction within the Se-Hg competition. Proposed exposure limit for Pd compounds is 0.03 mg/m3.It is highly important to make the difference between soluble Pd-salts and metallic Pd. Although simple and complex Pd-salts have obvious hepatotoxic and nephrotoxic effects, no biological incidences have been demonstrated for metallic Pd. This is important especially for its increasing use in dental alloys. Our own experiences on cell culture systems with powders of pure metallic Pd and Pd-containing dental alloys have never shown any influence on the cell viability and on the induction of inflammatory effects. Its biocompatibility is comparable to that of Au, Pt or Ti.In the last few years, however, Pd has caused a lot of controversial discussion with respect to its sensitizing effects. The present state-of-the-art of this problem is that Pd sensitization may coincide with Ni sensitization.
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PMID:Biological and hepatotoxic effects of palladium. An overview on experimental investigations and personal studies. 2351 34

Molecular detection of herbicide non-target-site-based resistance (NTSR) classically requires extensively validated NTSR genes. We assessed the feasibility of predicting NTSR phenotypes using expression data of NTSR transcriptional markers, i.e., transcripts which expression levels are statistically correlated to NTSR. Markers were sought by comparative RNA-Seq analysis of untreated NTSR or sensitive plants from four rye-grass populations followed by expression quantification in 299 individual plants with characterised sensitivity to two acetolactate-synthase-inhibiting herbicides. Multivariate analyses were implemented to predict NTSR using combined marker expression data. Nineteen markers (four cytochromes P450, four glutathione-S-transferases, three glycosyltransferases, two ABC transporters, two hydrolases, one aldolase, one peptidase, one transferase and one esterase) expressed significantly higher in NTSR plants were identified. Expression was highest in the most resistant plants. Some markers appeared co-regulated. Combined marker expression data enabled prediction of NTSR phenotypes in individual plants or of resistant plant frequencies in populations. Thus, NTSR detection based on transcriptional markers proved feasible. Accuracy can be improved by identifying additional markers, especially markers associated to NTSR regulation. Additionally, our data suggest that NTSR mechanisms emerged in different populations via redundant evolution, and that NTSR can evolve by selection for higher constitutive expression of whole herbicide-response pathways.
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PMID:Transcriptional markers enable identification of rye-grass (Lolium sp.) plants with non-target-site-based resistance to herbicides inhibiting acetolactate-synthase. 2822 16