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- Billod, Jean-Marc, et al.
(författare)
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Structures, Properties, and Dynamics of Intermediates in eEF2-Diphthamide Biosynthesis
- 2016
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Ingår i: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 56:9, s. 1776-1786
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Tidskriftsartikel (refereegranskat)abstract
- The eukaryotic translation Elongation Factor 2 (eEF2) is an essential enzyme in protein synthesis. eEF2 contains a unique modification of a histidine (His699 in yeast; HIS) into diphthamide (DTA), obtained via 3-amino-3-carboxypropyl (ACP) and diphthine (DTI) intermediates in the biosynthetic pathway. This essential and unique modification is also vulnerable, in that it can be efficiently targeted by NAD(+)-dependent ADP-ribosylase toxins, such as diphtheria toxin (DT). However, none of the intermediates in the biosynthesis path is equally vulnerable against the toxins. This study aims to address the different susceptibility of DTA and its precursors against bacterial toxins. We have herein undertaken a detailed in silico study of the structural features and dynamic motion of different His699 intermediates along the diphthamide synthesis pathway (HIS, ACP, DTI, DTA). The study points out that DTA forms a strong hydrogen bond with an asparagine which might explain the ADP-ribosylation mechanism caused by the diphtheria toxin (DT). Finally, in silico mutagenesis studies were performed on the DTA modified protein, in order to hamper the formation of such a hydrogen bond. The results indicate that the mutant structure might in fact be less susceptible to attack by DT and thereby behave similarly to DTI in this respect.
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| 2. |
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| 3. |
- Grahnemo, Louise, et al.
(författare)
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Identification of three bacterial species associated with increased appendicular lean mass : the HUNT study.
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Appendicular lean mass (ALM) associates with mobility and bone mineral density (BMD). While associations between gut microbiota composition and ALM have been reported, previous studies rely on relatively small sample sizes. Here, we determine the associations between prevalent gut microbes and ALM in large discovery and replication cohorts with information on relevant confounders within the population-based Norwegian HUNT cohort (n = 5196, including women and men). We show that the presence of three bacterial species - Coprococcus comes, Dorea longicatena, and Eubacterium ventriosum - are reproducibly associated with higher ALM. When combined into an anabolic species count, participants with all three anabolic species have 0.80 kg higher ALM than those without any. In an exploratory analysis, the anabolic species count is positively associated with femoral neck and total hip BMD. We conclude that the anabolic species count may be used as a marker of ALM and BMD. The therapeutic potential of these anabolic species to prevent sarcopenia and osteoporosis needs to be determined.
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| 4. |
- Molin, Mikael, 1973, et al.
(författare)
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Protein kinase A controls yeast growth in visible light
- 2020
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Ingår i: BMC Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: A wide variety of photosynthetic and non-photosynthetic species sense and respond to light, having developed protective mechanisms to adapt to damaging effects on DNA and proteins. While the biology of UV light-induced damage has been well studied, cellular responses to stress from visible light (400–700 nm) remain poorly understood despite being a regular part of the life cycle of many organisms. Here, we developed a high-throughput method for measuring growth under visible light stress and used it to screen for light sensitivity in the yeast gene deletion collection. Results: We found genes involved in HOG pathway signaling, RNA polymerase II transcription, translation, diphthamide modifications of the translational elongation factor eEF2, and the oxidative stress response to be required for light resistance. Reduced nuclear localization of the transcription factor Msn2 and lower glycogen accumulation indicated higher protein kinase A (cAMP-dependent protein kinase, PKA) activity in many light-sensitive gene deletion strains. We therefore used an ectopic fluorescent PKA reporter and mutants with constitutively altered PKA activity to show that repression of PKA is essential for resistance to visible light. Conclusion: We conclude that yeast photobiology is multifaceted and that protein kinase A plays a key role in the ability of cells to grow upon visible light exposure. We propose that visible light impacts on the biology and evolution of many non-photosynthetic organisms and have practical implications for how organisms are studied in the laboratory, with or without illumination.
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