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The Modification of Lysine
Published in Roger L. Lundblad, Chemical Reagents for Protein Modification, 2020
On occasion, the modification of an amino acid residue in a protein is associated with an apparent increase in catalytic activity. This was the situation with the modification of 14S and 30S dynein adenosine triphosphatase activities with trinitrobenzenesulfonic acid.129 In this study, the reaction was performed in 0.030 M barbital, pH 8.5 at 25°C. The extent of modification was determined spectrophotometrically at 345 nm (∊ = 1.45 x 104M−1 cm−1). In studies similar to those obtained with glutamate dehydrogenase as discussed above,124 glutathione reductase was demonstrated to reduce trinitrobenzenesulfonate.130 Inhibition of glutathione reductase was noted at low concentration (0.05 μM) of trinitrobenzenesulfonate.
Keratin
Published in Masahiko Mori, Histochemistry of the Salivary Glands, 2019
Myoepithelial cells or basket cells surround acinar cells or intercalated ducts. Enzyme-histochemically, they demonstrate alkaline phosphatase and/or adenosine triphosphatase activities.45 Immunohistochemically, they display myosin or actin proteins as contractive proteins. Immunohistochemically detectable keratins in myoepithelial cells have been identified by recognizing particular keratin polypeptides, and at the same time ductal basal cells are identified (Table 6). A specific keratin antibody for detecting myoepithelial cell has been reported by many authors. The monoclonal antibody stained either myoepithelial cells only, or myoepithelial and ductal basal cells. (Table 6)
Mutagenic Consequences Of Chemical Reaction with DNA
Published in Philip L. Grover, Chemical Carcinogens and DNA, 2019
Radman and co-workers have developed an in vitro assay for mutation.104 The system involves a synthetic template (currently poly dC oligo dG, formerly poly dT oligo dA). If replication on the template occurs, only one type of base should be inserted. Insertion of A instead of G (or vice versa) gives a measure of the accuracy of replication. It is possible to add to the system a variety of cell extracts obtained under different conditions in order to look for evidence of an inducible error-prone polymerase activity. Since only two triphosphates are needed to assay correct and incorrect synthesis on the template, it is possible to omit the other triphosphates and reduce synthesis on residual DNA present in the extracts. Using this system, Radman et al.107 obtained evidence of increased misincorporation using extracts of a tif strain prepared at elevated temperature. Recently, however, McGarva and Lehmann108 have shown the presence of a DNA-dependent triphosphatase in such extracts,27 which could cause serious artefacts, and the validity of this exciting in vitro approach to mutagenesis remains to be established.
Crotonaldehyde exposure induces liver dysfunction and mitochondrial energy metabolism disorder in rats
Published in Toxicology Mechanisms and Methods, 2021
Shuman Zhang, Biao Zhang, Qi Zhang, Zhihu Zhang
Mammalian mtDNA encodes the protein subunits of 13 ETC complexes, which are essential for the function of the OXPHOS system, cell function, and biological health (Murphy and Smith 2000). mtDNA is fragile, hence any damage to it results in altered function of mitochondrial OXPHOS (Scheibye-Knudsen et al. 2015; Gustafsson et al. 2016; Van Houten et al., 2016). C V is a key enzyme in ATP synthesis and ATPase6 gene is a subunit of the Fo functional region of the mtDNA encoding C V, which is primarily involved in ATP synthesis. A decrease in ATPase6 gene expression can cause changes in the expression of F0F1 adenosine triphosphatase protein, thereby inducing mitochondrial energy metabolism disorders (Zhang et al. 2010). Real-time PCR showed that crotonaldehyde exposure inhibited the expression of ATPase6 in rat liver mitochondria, which ultimately reduced ATP levels; in addition, crotonaldehyde exposure inhibited the expression of ND1, ND2, Cyt-b, COX1, and COX3 in rat liver mitochondria. These results indicate that crotonaldehyde exposure can disrupt mtDNA transcription, damage the structure and function of liver mitochondria, disturb the mtDNA encoded ETC complex, inhibit the activity of the ETC complex, interfere with energy metabolism, and promote liver damage.
The latest automated docking technologies for novel drug discovery
Published in Expert Opinion on Drug Discovery, 2021
In other interesting work, Scafuri et al [61] applied a reverse docking protocol to generate a list of human proteins potentially bound by apple phenolic compounds with colorectal cancer chemo-preventive effects. They found that the proteins guanosine triphosphatase, guanosine 5′-monophosphate oxidoreductase, and hypoxanthine-guanine phosphoribosyltransferase might be the key targets for these compounds. In other work, Maccari et al [62] used a target fishing procedure based on shape similarity, reverse docking, and consensus score to investigate the mode of action of macrocyclic amidinoureas previously identified as antifungal agents. They found that chitinase represents at least one of the main targets of the studied macrocyclic amidinoureas. In other work, Lee and Kim [63] developed the fully automated web tool CRDS (Consensus Reverse Docking System) for target fishing. This tool predicts potential interaction sites for a given drug. In a search, the web server provides the list of top 50 predicted interaction sites, docking conformations, 10 most significant pathways, and the distribution of consensus scores based on the combination of three different scoring functions.
New insights into targeting hepatic cystogenesis in autosomal dominant polycystic liver and kidney disease
Published in Expert Opinion on Therapeutic Targets, 2020
Thijs R. M. Barten, Lucas H. P. Bernts, Joost P. H. Drenth, Tom J. G. Gevers
Lovastatin (an HMG-COA reductase inhibitor) prevents cell proliferation by inhibiting the conversion of acetyl-CoA to farnesyl pyrophosphate (FPP). FPP is required for the activation of guanosine triphosphatase binding proteins that cause cell proliferation in mammalian cells [83]. Treating Han:SPRD rats (a rodent model for ADPKD) with lovastatin leads to structural changes in renal composition, including decreased cystic kidney size and volume density of cysts [83,84]. In addition, another statin (pravastatin) was effective in slowing the progression of structural kidney disease in children with ADPKD [85]. In contrast, a recent post-hoc analysis of the HALT-PKD trial found no differences in TKV and TLV between patients with and without statins. However, limitations of this post-hoc analysis were the small number of statin users, the use of different statin types and non-randomized allocation of doses [86], which precludes definitive answers on the effect of statins on hepatic and renal cystogenesis. The efficacy of pravastatin is currently investigated in adult ADPKD patients (ClinicialTrials.gov Identifier NCT03273413), in a trial that will compare the effect of pravastatin 40 mg with placebo on TKV in ADPKD patients, but does not include hepatic outcomes.