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| 2. |
- Schütz, Patrick, et al.
(författare)
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Comparative structural analysis of human DEAD-box RNA helicases
- 2010
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:9
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Tidskriftsartikel (refereegranskat)abstract
- DEAD-box RNA helicases play various, often critical, roles in all processes where RNAs are involved. Members of this family of proteins are linked to human disease, including cancer and viral infections. DEAD-box proteins contain two conserved domains that both contribute to RNA and ATP binding. Despite recent advances the molecular details of how these enzymes convert chemical energy into RNA remodeling is unknown. We present crystal structures of the isolated DEAD-domains of human DDX2A/eIF4A1, DDX2B/eIF4A2, DDX5, DDX10/DBP4, DDX18/myc-regulated DEAD-box protein, DDX20, DDX47, DDX52/ROK1, and DDX53/CAGE, and of the helicase domains of DDX25 and DDX41. Together with prior knowledge this enables a family-wide comparative structural analysis. We propose a general mechanism for opening of the RNA binding site. This analysis also provides insights into the diversity of DExD/H- proteins, with implications for understanding the functions of individual family members.
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| 4. |
- Bota, András, et al.
(författare)
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Socioeconomic and environmental patterns behind H1N1 spreading in Sweden
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the critical factors related to influenza spreading is crucial in predicting and mitigating epidemics. Specifically, uncovering the relationship between epidemic onset and various risk indicators such as socioeconomic, mobility and climate factors can reveal locations and travel patterns that play critical roles in furthering an outbreak. We study the 2009 A(H1N1) influenza outbreaks in Sweden’s municipalities between 2009 and 2015 and use the Generalized Inverse Infection Method (GIIM) to assess the most significant contributing risk factors. GIIM represents an epidemic spreading process on a network: nodes correspond to geographical objects, links indicate travel routes, and transmission probabilities assigned to the links guide the infection process. Our results reinforce existing observations that the influenza outbreaks considered in this study were driven by the country’s largest population centers, while meteorological factors also contributed significantly. Travel and other socioeconomic indicators have a negligible effect. We also demonstrate that by training our model on the 2009 outbreak, we can predict the epidemic onsets in the following five seasons with high accuracy.
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| 5. |
- Collins, Ruairi, et al.
(författare)
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Biochemical discrimination between selenium and sulfur 1 : a single residue provides selenium specificity to human selenocysteine lyase
- 2012
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Ingår i: PLoS One. - Stockholm : Karolinska Institutet, Dept of Medical Biochemistry and Biophysics. - 1932-6203.
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Tidskriftsartikel (refereegranskat)abstract
- Selenium and sulfur are two closely related basic elements utilized in nature for a vast array of biochemical reactions. While toxic at higher concentrations, selenium is an essential trace element incorporated into selenoproteins as selenocysteine (Sec), the selenium analogue of cysteine (Cys). Sec lyases (SCLs) and Cys desulfurases (CDs) catalyze the removal of selenium or sulfur from Sec or Cys and generally act on both substrates. In contrast, human SCL (hSCL) is specific for Sec although the only difference between Sec and Cys is the identity of a single atom. The chemical basis of this selenium-over-sulfur discrimination is not understood. Here we describe the X-ray crystal structure of hSCL and identify Asp146 as the key residue that provides the Sec specificity. A D146K variant resulted in loss of Sec specificity and appearance of CD activity. A dynamic active site segment also provides the structural prerequisites for direct product delivery of selenide produced by Sec cleavage, thus avoiding release of reactive selenide species into the cell. We thus here define a molecular determinant for enzymatic specificity discrimination between a single selenium versus sulfur atom, elements with very similar chemical properties. Our findings thus provide molecular insights into a key level of control in human selenium and selenoprotein turnover and metabolism.
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| 6. |
- Karlberg, Tobias, et al.
(författare)
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Structure of human argininosuccinate synthetase.
- 2008
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Ingår i: Acta Crystallogr D Biol Crystallogr. - 0907-4449. ; 64:Pt 3, s. 279-86
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Tidskriftsartikel (refereegranskat)abstract
- Argininosuccinate synthetase catalyzes the transformation of citrulline and aspartate into argininosuccinate and pyrophosphate using the hydrolysis of ATP to AMP and pyrophosphate. This enzymatic process constitutes the rate-limiting step in both the urea and arginine-citrulline cycles. Previous studies have investigated the crystal structures of argininosuccinate synthetase from bacterial species. In this work, the first crystal structure of human argininosuccinate synthetase in complex with the substrates citrulline and aspartate is presented. The human enzyme is compared with structures of argininosuccinate synthetase from bacteria. In addition, the structure also provides new insights into the function of the numerous clinical mutations identified in patients with type I citrullinaemia (also known as classic citrullinaemia).
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| 8. |
- Perez-Valera, Mario, et al.
(författare)
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Angiotensin-Converting Enzyme 2 (SARS-CoV-2 receptor) expression in human skeletal muscle
- 2021
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 31:12, s. 2249-2258
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Tidskriftsartikel (refereegranskat)abstract
- The study aimed to determine the levels of skeletal muscle Angiotensin-Converting Enzyme 2 (ACE2, the SARS-CoV-2 receptor) protein expression in men and women and assess whether ACE2 expression in skeletal muscle is associated with cardiorespiratory fitness and adiposity. The level of ACE2 in vastus lateralis muscle biopsies collected in previous studies from 170 men (age:19-65 yrs, weight:56-137 kg, BMI:23-44) and 69 women (age:18-55 yrs, weight:41-126 kg, BMI:22-39) was analysed in duplicate by western blot. VO2max was determined by ergospirometry and body composition by DXA. ACE2 protein expression was 1.8-fold higher in women than men (p=0.001, n=239). This sex difference disappeared after accounting for the percentage of body fat (fat %), VO2max per kg of legs lean mass (VO2max-LLM) and age (p=0.47). Multiple regression analysis showed that the fat % (β=0.47) is the main predictor of the variability in ACE2 protein expression in skeletal muscle, explaining 5.2 % of the variance. VO2max-LLM had also predictive value (β=0.09). There was a significant fat % by VO2max-LLM interaction, such that for subjects with low fat %, VO2max-LLM was positively associated with ACE2 expression while as fat % increased the slope of the positive association between VO2max-LLM and ACE2 was reduced. In conclusion, women express higher amounts of ACE2 in their skeletal muscles than men. This sexual dimorphism is mainly explained by sex differences in fat % and cardiorespiratory fitness. The percentage of body fat is the main predictor of the variability in ACE2 protein expression in human skeletal muscle.
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| 9. |
- Abbas, Zareen, 1962, et al.
(författare)
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Synthesis, characterization and particle size distribution of TiO2 colloidal nanoparticles
- 2011
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Ingår i: Colloids and Surfaces A: Physicochemical and Engineering Aspects. - : Elsevier BV. - 0927-7757. ; 384:1-3, s. 254-261
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Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles of controlled size, well defined shape, pure phase and of clean surfaces are ideal model systems to investigate surface/interfacial reactions. In this study we have explored the possibility of synthesizing TiO2 nanoparticles in the size range of 7–20 nm under well controlled experimental conditions. A simple method based on the hydrolysis of TiCl4 was used to obtain particles having surfaces free from organics. Stable dispersions of TiO2 nanoparticles of various sizes were obtained by optimizing the reaction/dialysis time and temperature. The synthesized TiO2 particles were found to be predominantly of anatase phase and narrow particle size distributions were obtained. The TiO2 particles were characterized with respect to their phase, size and shape by X-ray diffraction (XRD) and transmission electron microscopy (TEM), respectively. Particle size distribution in a colloidal dispersion was obtained by the electrospray scanning mobility particle sizer (ES-SMPS) method and compared with an average particle size determined from dynamic light scattering (DLS). The average particle sizes obtained by the DLS and ES-SMPS methods were in good agreement, while a primary particle size of 4 nm was found in X-ray diffraction irrespective of the particle size in solution. Early stages of the nucleation process were monitored by the ES-SMPS method. These results show that small particles of 4–5 nm are initially formed and it is highly likely that large particles are formed due to aggregation of primary particles.
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