China
Africa
Explore chapters and articles related to this topic
Coat Protein
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
As it appears from Table 12.1, the amino acid-sequenced coats were always shorter for one amino acid residue than their counterparts deduced from the nucleotide sequence. This discrepancy was explained finally when Housman et al. (1972) found that the N-terminal formylmethionine was removed when the nascent chain of the phage f2 coat protein reached 40–60 amino acids in length. It was known before that all protein synthesized in vitro in the cell-free E. coli extracts retained an N-terminal formylmethionine or methionine residue (Lengyel and Soll 1969). By contrast, no completed protein isolated from growing E. coli cells contained formylmethionine as its N-terminal residue, and only 30% had an N-terminal methionine (Waller 1963). Since growing E. coli cells initiated protein synthesis with formyl-methionine tRNA (Eisenstadt and Lengyel 1966), these results suggested that the cell-free extracts were defective in the enzyme or enzymes which normally removed the amino-terminal formylmethionine or formyl residues (Adams and Capecchi 1966; Capecchi 1966b; Webster et al. 1966). The emotional moment of this important point was touched on in Chapter 1. Once and for all, Housman et al. (1972) showed clearly that the f2 coat protein synthesized by an infected cell was initiated with the N-terminal sequence fMet-Ala-Ser…, but the N-terminal fMet residue was removed while the polypeptide chain was still nascent.
The N-Formylpeptide Chemotactic Receptor
Published in Richard Horuk, Chemoattractant Ligands and Their Receptors, 2020
The natural agonists for FPR may not be limited to foreign oligopeptides. Mitochondria contain a separate genome with thirteen genes whose products also start with N-formylmethionine. At least one of these proteins has phagocyte chemoat-tractant activity.24 Moreover, it has been shown that synthetic N-formyl oligopeptides matching the N-terminal sequence of the mouse mitochondrially encoded subunit of NADH dehydrogenase can potently induce elastase release from rabbit neutrophils.25 Thus, one could easily imagine that mitochondrial N-formylpeptides released from dying cells at sites of tissue damage could attract phagocytes to the area to begin the process of tissue repair. This is still highly speculative, since it is not yet known whether N-formyl oligopeptides derived from mitochondrial proteins actually occur extracellularly in nature. Moreover, whether the activity is mediated by FPR or another related receptor has not been tested directly.
O
Published in Anton Sebastian, A Dictionary of the History of Medicine, 2018
Ochoa, Severo (b 1905) American geneticist, born in Spain and worked in Heidelberg and Oxford before emigrating to the USA to take up a post at Washington University Medical School. He later moved to the NewYork University School of Medicine. He isolated two enzymes from the Krebs cycle and polynucleotide phosphorylase, determined a number of genetic codons, studied protein synthesis and initiating factors in binding of N-formylmethionine. He was awarded the 1959 Nobel Prize for Physiology or Medicine, together with Arthur Kornberg (b 1918). See nucleic acids.
Biomarkers of oxidative stress in urine and plasma of operators at six Singapore printing centers and their association with several metrics of printer-emitted nanoparticle exposures
Published in Nanotoxicology, 2022
Dhimiter Bello, Lucia Chanetsa, Costas A. Christophi, Dilpreet Singh, Magdiel Inggrid Setyawati, David C. Christiani, Sanjay H. Chotirmall, Kee Woei Ng, Philip Demokritou
Global serum metabolomics was recently completed on the same set of 19 healthy TPE operators, 11 of whom were followed a year later (Jia et al. 2022). Significant exposure-dependent dysregulation of 52 metabolites was documented, with the highest dysregulation observed for the highest PEPs exposure group. This included several important upregulated biomolecules in the arginine, phenylalanine, tryptophan, histidine, and glutathione metabolism. Metabolites such as L-aspartate, L-proline, L-citrulline, 5-hydroxy-L-tryptophan, L-kynurenine, kyrurenic acid, Indolelactic acid, quinolinic acid, are involved in several important biochemical processes related to OS, inflammation, and immune response modulation. Significant cross-week increases were documented in several important metabolites, including L-lysine, choline, tyrosine, pyroglutamic acid, L-methionine, L-serine, L-aspartate, and N-formylmethionine. Collectively, these metabolites contribute to ROS scavenging and pro-oxidant activity, upregulation and stabilization of antioxidant defense mechanisms, including glutathione synthesis, and enhancement of immune responses to protect against PEPs-induced toxicity. Uric acid, a major serum antioxidant, was also found significantly elevated in workers’ serum, presumably as a compensatory antioxidant mechanism for the reduced pool of precursors in the glutathione synthesis. However, with time, the initial compensatory mechanisms will fail to keep up with continued insult giving way to more oxidative damage and inflammation. This overall conclusion is supported by global metabolomic analysis of the 11 workers in the 1-year follow-up, which identified 20 additional differentially expressed metabolites. Several of these metabolites that are involved in the antioxidant defense mechanisms, notably including L-cystine, indole-3-acetic acid, L-glutamine, and L-asparagine, were downregulated after an additional year of PEPs exposure, whereas the opposite was true for the metabolites involved in the inflammatory responses (upregulated).
The increasing importance of the novel Coronavirus
Published in Hospital Practice, 2021
Mohammad Ridwane Mungroo, Naveed Ahmed Khan, Ruqaiyyah Siddiqui
New treatment options can be discovered faster using drug repurposing rather than searching for novel drugs as the safety profiles for approved drugs are readily accessible. Bioinformatics can be used to effectively identify appropriate drugs for repurposing purposes by analyzing the interactions between dugs with proteins of SARS-CoV-2, the target organism. The use of bioinformatics recently led to the identification of 78 drugs as possible repurposed drugs that could target SARS-CoV-2 [71]. After being refined by eliminating drugs deemed unsuitable for repurposing, based on their side effects and influence on symptoms of SARS-CoV-2, the list was updated to 30 drugs [71]. Pseudoephedrine, Atiprimod, Adalimumab, Tapinarof, Epinephrine, Thalidomide, YSIL6, Infliximab, Andrographolide, Pranlukast, Afelimomab, Siltuximab, Ibalizumab, Abacavir, Etanercept, Golimumab, Cefazolin, Proline, Chloroquine, N-Formylmethionine, Framycetin, Olsalazine, Vicriviroc, Ruplizumab, Artenimol, Clenbuterol, Quercetin, Myricetin, Ketoprofen and Maraviroc are the 30 compounds recognized as potential compounds for repurposing versus SARS-CoV-2 [71]. Bioinformatic tools were also used in another study to elucidate existing compounds that may be appropriate candidates for repurposing against SARS-CoV-2. 15 approved compounds, 4 compounds being tested in phase 1 clinical trials and 18 compounds currently in the pre-clinical stage were elucidated using chemoinformatics while 12 approved compounds, 10 being tested in phase 1 clinical trials and 10 compounds currently in the pre-clinical stage were discovered via specialist knowledge [72]. 3 C-like protease, a 33.8kDa protease, identified as the main protease of SARS-CoV has been described as essential for the transcription and replication of the virus owing to its pivotal role in the processing of pp1a and pp1ab, 2 replicase polyproteins [73]. By using computer-aided drug design, the crystal structure of SARS-CoV-2 main protease was determined and using virtual and high-throughput screening based on the crystalline structure, 6 compounds that can inhibit the activity of the SARS-CoV-2 main protease with IC50 values between 0.67 μM and 21.4 μM were identified [74]. 2 of the compounds, namely disulfiram and carmofur are drugs that are approved by the Food and Drug Administration, and Ebselen, PX-12, Shikonin and Tideglusib are currently undergoing preclinical or clinical trials [74]. It was also demonstrated in vitro that Ebselen displayed activity against SARS-CoV-2 with EC50 value of 4.67 μM, suggesting that it might serve as a potential anti-SARS-CoV-2 drug [74].