排序方式: 共有144条查询结果,搜索用时 67 毫秒
141.
Ol’ha O. Brovarets’ Ivan S. Voiteshenko Horacio Pérez-Sánchez Dmytro M. Hovorun 《Journal of biomolecular structure & dynamics》2018,36(7):1649-1665
This work is devoted to the careful QM/QTAIM analysis of the evolution of the basic physico-chemical parameters along the intrinsic reaction coordinate (IRC) of the biologically important 2AP·T(WC)?2AP·T*(w) and 2AP·C*(WC)?2AP·C(w) Watson–Crick(WC)?wobble(w) tautomeric transformations obtained at each point of the IRC using original authors’ methodology. Established profiles reflect the high similarity between the courses of these processes. Basing on the scrupulous analysis of the profiles of their geometric and electron-topological parameters, it was established that the dipole-active WC?w tautomerizations of the Watson–Crick-like 2AP·T(WC)/2AP·C*(WC) mispairs, stabilized by the two classical N3H?N1, N2H?O2 and one weak C6H?O4/N4 H-bonds, into the wobble 2AP·T*(w)/2AP·C(w) base pairs, respectively, joined by the two classical N2H?N3 and O4/N4H?N1 H-bonds, proceed via the concerted stepwise mechanism through the sequential intrapair proton transfer and subsequent large-scale shifting of the bases relative each other, through the planar, highly stable, zwitterionic transition states stabilized by the participation of the four H-bonds – N1+H?O4–/N4–, N1+H?N3–, N2+H?N3–, and N2+H?O2–. Moreover, it was found out that the 2AP·T(WC)?2AP·T*(w)/2AP·C*(WC)?2AP·C(w) tautomerization reactions occur non-dissociatively and are accompanied by the consequent replacement of the 10 unique patterns of the specific intermolecular interactions along the IRC. Obtained data are of paramount importance in view of their possible application for the control and management of the proton transfer, e.g. by external electric or laser fields. 相似文献
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Complete suppression of Htt fibrilization and disaggregation of Htt fibrils by a trimeric chaperone complex 下载免费PDF全文
Annika Scior Alexander Buntru Kristin Arnsburg Anne Ast Manuel Iburg Katrin Juenemann Maria Lucia Pigazzini Barbara Mlody Dmytro Puchkov Josef Priller Erich E Wanker Alessandro Prigione Janine Kirstein 《The EMBO journal》2018,37(2):282-299
Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat in the huntingtin gene (HTT). Molecular chaperones have been implicated in suppressing or delaying the aggregation of mutant Htt. Using in vitro and in vivo assays, we have identified a trimeric chaperone complex (Hsc70, Hsp110, and J‐protein) that completely suppresses fibrilization of HttExon1Q48. The composition of this chaperone complex is variable as recruitment of different chaperone family members forms distinct functional complexes. The trimeric chaperone complex is also able to resolubilize Htt fibrils. We confirmed the biological significance of these findings in HD patient‐derived neural cells and on an organismal level in Caenorhabditis elegans. Among the proteins in this chaperone complex, the J‐protein is the concentration‐limiting factor. The single overexpression of DNAJB1 in HEK293T cells is sufficient to profoundly reduce HttExon1Q97 aggregation and represents a target of future therapeutic avenues for HD. 相似文献
144.
Diana Széliová Dmytro Iurashev David E Ruckerbauer Gunda Koellensperger Nicole Borth Michael Melcher Jürgen Zanghellini 《Biotechnology journal》2021,16(4):2000320
Chinese hamster ovary (CHO) cells are the most popular mammalian cell factories for the production of glycosylated biopharmaceuticals. To further increase titer and productivity and ensure product quality, rational system-level engineering strategies based on constraint-based metabolic modeling, such as flux balance analysis (FBA), have gained strong interest. However, the quality of FBA predictions depends on the accuracy of the experimental input data, especially on the exchange rates of extracellular metabolites. Yet, it is not standard practice to devote sufficient attention to the accurate determination of these rates. In this work, we investigated to what degree the sampling frequency during a batch culture and the measurement errors of metabolite concentrations influence the accuracy of the calculated exchange rates and further, how this error then propagates into FBA predictions of growth rates. We determined that accurate measurements of essential amino acids with low uptake rates are crucial for the accuracy of FBA predictions, followed by a sufficient number of analyzed time points. We observed that the measured difference in growth rates of two cell lines can only be reliably predicted when both high measurement accuracy and sampling frequency are ensured. 相似文献