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951.
952.
Nina Østergaard Knudsen Sofie Dabros Andersen Anne Lützen Finn Cilius Nielsen Lene Juel Rasmussen 《DNA Repair》2009,8(6):682-689
DNA mutations are circumvented by dedicated specialized excision repair systems, such as the base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR) pathways. Although the individual repair pathways have distinct roles in suppressing changes in the nuclear DNA, it is evident that proteins from the different DNA repair pathways interact [Y. Wang, D. Cortez, P. Yazdi, N. Neff, S.J. Elledge, J. Qin, BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures, Genes Dev. 14 (2000) 927–939; M. Christmann, M.T. Tomicic, W.P. Roos, B. Kaina, Mechanisms of human DNA repair: an update, Toxicology 193 (2003) 3–34; N.B. Larsen, M. Rasmussen, L.J. Rasmussen, Nuclear and mitochondrial DNA repair: similar pathways? Mitochondrion 5 (2005) 89–108]. Protein interactions are not only important for function, but also for regulation of nuclear import that is necessary for proper localization of the repair proteins. This review summarizes the current knowledge on nuclear import mechanisms of DNA excision repair proteins and provides a model that categorizes the import by different mechanisms, including classical nuclear import, co-import of proteins, and alternative transport pathways. Most excision repair proteins appear to contain classical NLS sequences directing their nuclear import, however, additional import mechanisms add alternative regulatory levels to protein import, indirectly affecting protein function. Protein co-import appears to be a mechanism employed by the composite repair systems NER and MMR to enhance and regulate nuclear accumulation of repair proteins thereby ensuring faithful DNA repair. 相似文献
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Yihui Chen Ana G. Petrovic Marin Roje Gennaro Pescitelli Margaret M. Kayser Yan Yang Nina Berova Gloria Proni 《Chirality》2010,22(1):140-152
This article describes an application of the host‐guest chiral recognition approach called tweezer methodology for the determination of the absolute configuration of 3‐hydroxy‐β‐lactams. These substrates represent challenging cases due to their chemical reactivity, the presence of multiple stereogenic centers and several functional groups which offer various possibilities of binding to the Zn‐porphyrin host. OPLS‐2005, the force field used in this work to predict the interporphyrin twist, modeled correctly the host‐guest complexation mechanism and revealed conformational details of the bound substrates. The computational study also suggested that in cases where an increase in the magnitude of the stereodifferentiation and an intense experimental CD are observed, the bound conformation of the conjugates are hydrogen bonded. The present investigation provides evidence that when the tweezer method is assisted by the OPLS‐2005 based computational approach, it can be successfully applied to the configurational and conformational elucidation of multi‐functional compounds with multiple stereogenic centers. Chirality, 2010. © 2009 Wiley‐Liss, Inc. 相似文献
958.
Peter Comba Nina Dovalil Gebhard Haberhauer Graeme R. Hanson Yuki Kato Toshiaki Taura 《Journal of biological inorganic chemistry》2010,15(7):1129-1135
The CuII coordination chemistry of three synthetic analogues of westiellamide (H3Lwa) with an [18]azacrown-6 macrocyclic structure and imidazole (H3L1), oxazole (H3L2), or thiazole (H3L3) heterocyclic donors in addition to the peptide groups, is reported. The Nheterocycle–Npeptide–Nheterocycle binding sites are highly preorganized for the coordination to CuII ions. The stability constants of mono- and dinuclear CuII complexes of H3L1, H3L2, and H3L3, obtained by isothermal titration microcalorimetry, are reported. EPR and NMR spectroscopy as well as electrospray ionization
mass spectrometry (ESI-MS) were used to characterize the complexes formed in solution. The stabilities of the mononuclear
and dinuclear CuII complexes of the three ligands are in the range of 105 M−1, but there are subtle differences; specifically the oxazole-derived ligand has, in contrast to the other two macrocycles,
a negative formation entropy for coordination to the first CuII ion and a higher stability for complexation to a second CuII center in comparison with the first CuII center (cooperativity). Differences between the three ligands are also apparent in terms of the formation mechanism. With
the oxazole-based ligand H3L2, NMR spectroscopy, EPR spectroscopy, and ESI-MS indicate the formation of a ligand–CuII 2:1 intermediate, and this may explain the differences in the formation entropy as well as the cooperativity. 相似文献
959.
Arctic charr are characterized by an extensive variability in growth and body size in natural waters. Although growth traits
may involve a significant heritable component, most of this intraspecific variation presumably is environmentally induced
and thus attributable to phenotypic plasticity. In the present study, size-at-age and length–weight relationship (body condition)
were assessed for three Finnish Arctic charr populations of different geographical origins and extreme size forms (a stunted
vs. two large-growing, predatory charr) held under standardized rearing conditions for 3 years (up to 37 months after hatching).
In particular, our interest was to investigate whether the differences in growth between the large and the stunted charr as
observed in the wild populations would diminish when the fish are offered suitable food in abundance. Population-specific
mean body size and condition differed significantly in 0+, 1+, 2+ and 3+ fish. However, the identical rearing conditions resulted
in the originally stunted charr reaching a comparable final mean size (317 mm/427 g) as the large charr populations (343 mm/510 g
and 359 mm/497 g). Some individuals were of the same size as their parents at spawning already at the age of 0+ years. Furthermore,
length–weight regression residuals of the stunted charr developed to a notably high level, indicating the largest final condition
mean. The increase of size variation (CV of weight) in stunted charr lasted for over two growth seasons, whereas in large
charr it remained stable since the end of the first summer. Variations in mortality and sexual maturation at age 2 seemed
to be less relevant factors affecting overall growth performance. The study demonstrates an example of the high plasticity
involved in the growth of fish: the stunted charr possess a tremendous capacity for growth in a benign environment, virtually
corresponding to that observed in the large predatory populations. 相似文献
960.
Jelena M. Aćimović Bojana D. Stanimirović Nina Todorović Vesna B. Jovanović Ljuba M. Mandić 《Chemico-biological interactions》2010,188(1):21-30
Methylglyoxal (MG), a reactive α-oxoaldehyde that is produced in higher quantities in diabetes, uremia, oxidative stress, aging and inflammation, reacts with the thiol groups (in addition to the amino and guanidino groups) of proteins. This causes protein modification, formation of advanced glycated end products (AGEs) and cross-linking. Low molecular mass thiols can be used as competitive targets for MG, preventing the reactions mentioned above. Therefore, this paper investigated how the microenvironment of the thiol group in low molecular mass thiols (cysteine, N-acetylcysteine (NAcCys), carboxymethylcysteine (CMC) and glutathione (GSH)) and human serum albumin (HSA) affected the thiol reaction with MG. The SH group reaction course was monitored by 1H-NMR spectroscopy and spectrophotometric quantification. Changes in the HSA molecules were monitored by SDS-PAGE. The microenvironment of the SH group had a major effect on its reactivity and on the product yield. The reactivity of SH groups decreased in the order Cys > GSH > NAcCys. CMC did not react. The percentages of the reacted SH groups in the equilibrium state were almost equal, regardless of the ratio of thiol compound/MG (1:1, 1:2, 1:5): 38.1 ± 0.9%; 38.2 ± 0.7% and 39.0 ± 0.8% for Cys; 26.5 ± 0.6%; 26.6 ± 2.6% and 27.4 ± 2.5% for GSH; 10.8 ± 0.9%; and 11.2 ± 0.7% and 12.2 ± 0.9% for NAcCys, respectively. Our results explain why substances containing α-amino-β-mercapto-ethane as a pharmacophore are successful scavengers of MG. In equilibrium, HSA SH reacted in high percentages both with an insufficient amount and with an excess of MG (55% and 65%, respectively). An analysis of the hydrophobicity of the microenvironment of the SH group on the HSA surface showed that it could contribute to high levels of SH modification, leading to an increase in the scavenging activity of the albumin thiol. 相似文献