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- Albers, Eva, 1966
(författare)
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Metabolic characteristics and importance of the universal methionine salvage pathway recycling methionine from 5'-methylthioadenosine
- 2009
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Ingår i: IUBMB Life. - : Wiley. - 1521-6543 .- 1521-6551. ; 61:12, s. 1132-1142
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Tidskriftsartikel (refereegranskat)abstract
- The methionine salvage pathway, also called the 5'-methylthioadenosine (MTA) cycle, recycles the sulfur of MTA, which is a by-product in the biosyntheses of polyamine and the plant hormone ethylene. MTA is first converted to 5'-methylthioribose-1-phosphate either by MTA phosphorylase or the combined action of MTA nucleosidase and 5'-methylthioribose kinase. Subsequently, five additional enzymatic steps, catalyzed by four or five proteins, will form 4-methylthio-2-oxobutyrate, the deaminated form of methionine. The final transamination is achieved by transaminases active in the amino acid biosynthesis. This pathway is present with some variations in all types of organisms and seems to be designed for a quick removal of MTA achieved by high affinities of the first enzymes. During evolution some enzymes have attained additional functions, like a proposed role in nuclear mRNA processing by the aci-reductone dioxygenase. For others the function seems to be lost due to conditions in specific ecological niches, such as, presence of sulfur and/or absence of oxygen resulting in that, for example,Escherichia coli is lacking a functional pathway. The pathway is regulated as response to sulfur availability and take part in the regulation of polyamine synthesis. Some of the enzymes in the pathway show separate specificities in different organisms and some others are unique for groups of bacteria and parasites. Thus, promising targets for antimicrobial agents have been identified. Other medical topics to which this pathway has connections are cancer, apoptosis, and inflammatory response.
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- Aydın, Efe, et al.
(författare)
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A hybrid approach to assess the structural impact of long noncoding RNA mutations uncovers key NEAT1 interactions in colorectal cancer
- 2023
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Ingår i: IUBMB Life. - : Wiley. - 1521-6543 .- 1521-6551. ; 75:7, s. 566-579
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Tidskriftsartikel (refereegranskat)abstract
- Long noncoding RNAs (lncRNAs) are emerging players in cancer and they entail potential as prognostic biomarkers or therapeutic targets. Earlier studies have identified somatic mutations in lncRNAs that are associated with tumor relapse after therapy, but the underlying mechanisms behind these associations remain unknown. Given the relevance of secondary structure for the function of some lncRNAs, some of these mutations may have a functional impact through structural disturbance. Here, we examined the potential structural and functional impact of a novel A > G point mutation in NEAT1 that has been recurrently observed in tumors of colorectal cancer patients experiencing relapse after treatment. Here, we used the nextPARS structural probing approach to provide first empirical evidence that this mutation alters NEAT1 structure. We further evaluated the potential effects of this structural alteration using computational tools and found that this mutation likely alters the binding propensities of several NEAT1-interacting miRNAs. Differential expression analysis on these miRNA networks shows upregulation of Vimentin, consistent with previous findings. We propose a hybrid pipeline that can be used to explore the potential functional effects of lncRNA somatic mutations.
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| 7. |
- Dunlop, Rachael A, et al.
(författare)
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Oxidized Proteins : Mechanisms of Removal and Consequences of Accumulation
- 2009
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Ingår i: IUBMB LIFE. - : Wiley. - 1521-6543 .- 1521-6551. ; 61:5, s. 522-527
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Tidskriftsartikel (refereegranskat)abstract
- Elevated levels of oxidized proteins are reported in diseased tissue from age-related pathologies such as atherosclerosis, neurodegenerative disorders, and cataract. Unlike the precise mechanisms that exist For the repair of nucleic acids, lipids, and carbohydrates, the primary pathway for the repair of oxidized proteins is complete catabolism to their constitutive amino acids. This process can be inefficient as is evidenced by their accumulation. It is generally considered that damaged proteins are degraded by the proteasome, however, this is only true for mildly oxidized proteins, because substrates must be unfolded to enter the narrow catalytic core. Rather, evidence suggests that moderately or heavily oxidized proteins are endocytosed and enter the endosomal/lysosomal system, indicating co-operation between the proteasomes and the lysosomes. Heavily modified substrates are incompletely degraded and accumulate within the lysosomal compartments resulting in the formation of lipofuscin-like, autofluorescent aggregates. Accumulation eventually results in impaired turnover of large organelles such as proteasomes and mitochondria, lysosomal destablization, leakage of proteases into the cytosol and apoptosis. In this review, we summarize reports published since our last assessments of the field of oxidized protein degradation including a role for modified proteins in the induction of apoptosis.
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| 9. |
- Gianni, Stefano, et al.
(författare)
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Conserved nucleation sites reinforce the significance of phi analysis in proteinfolding studies
- 2014
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Ingår i: IUBMB Life - A Journal of the International Union of Biochemistry and Molecular Biology. - : Wiley. - 1521-6543 .- 1521-6551. ; 66:7, s. 449-452
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Tidskriftsartikel (refereegranskat)abstract
- The only experimental strategy to address the structure of folding transition states, theso-called Φ value analysis, relies on the synergy between site directed mutagenesisand the measurement of reaction kinetics. Despite its importance, the Φ value analysishas been often criticized and its power to pinpoint structural information has beenquestioned. In this Hypothesis we demonstrate that comparing the Φ values betweenproteins not only allows highlighting the robustness of folding pathways, but alsoprovides per se a strong validation of the method.
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| 10. |
- Hughes, Diarmaid
(författare)
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Selection and Evolution of Resistance to Antimicrobial Drugs
- 2014
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Ingår i: IUBMB Life - A Journal of the International Union of Biochemistry and Molecular Biology. - : Wiley. - 1521-6543 .- 1521-6551. ; 66:8, s. 521-529
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Forskningsöversikt (refereegranskat)abstract
- The overuse and misuse of antibiotics over many years has selected a high frequency of resistance among medically important bacterial pathogens. The evolution of resistance is complex, frequently involving multiple genetic alterations that minimize biological fitness costs and/or increase the resistance level. Resistance is selected at very low drug concentrations, such as found widely distributed in the environment, and this selects for resistant mutants with a high fitness. Once resistance with high fitness is established in a community it is very difficult to reduce its frequency. Addressing the problem of resistance is essential if we are to ensure a future where we can continue to enjoy effective medical control of bacterial infections. This will require several actions including the discovery and development of novel antibiotics, the creation of a continuous pipeline of drug discovery, and the implementation of effective global antibiotic stewardship to reduce the misuse of antibiotics and their release into the environment.
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