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991.
992.
Bcl-XL is a pro-survival member of the Bcl-2 family that can be found in the outer mitochondrial membrane and in soluble cytosolic homodimers. Bcl-XL can bind pro-apoptotic members of this family preventing them from activating the execution phase of apoptosis. Bcl-XL has been shown to homodimerize in different ways, although most binding and structural assays have been carried out in the absence of its carboxyl terminal transmembrane domain. We show here that this domain can by itself direct protein oligomerization, which could be related to its previously reported role in mitochondrial morphology alterations and apoptosis inhibition. 相似文献
993.
Our understanding of the evolution of the insulin signaling pathway (ISP) is still incomplete. One intriguing unanswered question is the explanation of the emergence of the glucostatic role of insulin in mammals. To find out whether this is due to the development of new sets of signaling transduction elements in these organisms, or to the establishment of new interactions between pre-existing proteins, we rebuilt putative orthologous ISPs in 17 eukaryotic organisms. Then, we computed the conservation of orthologous ISPs at different levels, from sequence similarity of orthologous proteins to co-evolution of interacting domains. We found that the emergence of glucostatic role in mammals can neither be explained by the development of new sets of signaling elements, nor by the establishment of new interactions between pre-existing proteins. The comparison of orthologous IRS molecules indicates that only in mammals have they acquired their complete functionality as efficient recruiters of effector sub-pathways. 相似文献
994.
Sérgio M. Santos Sadaki Yokota Shrivallabh P. Kamat José A. S. Cavaleiro Tomonori Motokawa Tomomi Kato Mayu Mochizuki Toshiyuki Fujiwara Yuki Fujii Yoshitaka Tanaka 《Pigment cell & melanoma research》2014,27(3):376-386
Tyrosinase, a melanosomal membrane protein containing copper, is a key enzyme for melanin synthesis in melanocytes. Inulavosin inhibits melanogenesis by enhancing a degradation of tyrosinase in lysosomes. However, the mechanism by which inulavosin redirects tyrosinase to lysosomes is yet unknown. The analyses of structure–activity relationship of inulavosin and its benzo‐derivatives reveal that the hydroxyl and the methyl groups play a critical role in their inhibitory activity. Intriguingly, the docking studies to tyrosinase suggest that the compounds showing inhibitory activity bind through hydrophobic interactions to the cavity of tyrosinase below which the copper‐binding sites are located. This cavity is proposed to be required for the association with a chaperon that assists in copper loading to tyrosinase in Streptomyces antibioticus. Inulavosin and its benzo‐derivatives may compete with the copper chaperon and result in a lysosomal mistargeting of apo‐tyrosinase that has a conformational defect. 相似文献
995.
In higher plants, the PII protein is a nuclear-encoded plastid protein that regulates the activity of a key enzyme of arginine biosynthesis. We have previously observed that Arabidopsis PII mutants are more sensitive to nitrite toxicity. Using intact chloroplasts isolated from Arabidopsis leaves and (15)N-labelled nitrite we show that a light-dependent nitrite uptake into chloroplasts is increased in PII knock-out mutants when compared to the wild-type. This leads to a higher incorporation of (15)N into ammonium and amino acids in the mutant chloroplasts. However, the uptake differences do not depend on GS/GOGAT activities. Our observations suggest that PII is involved in the regulation of nitrite uptake into higher plant chloroplasts. 相似文献
996.
Effects of mechanical stress on Anammox granules in a sequencing batch reactor (SBR) 总被引:1,自引:0,他引:1
The effect of shear stress on Anammox process was studied in a sequencing batch reactor (SBR). The reactor was operated during 218 days under different stirring speeds (60-250 rpm) in order to expose the system to different shear conditions and to study the stability of the Anammox granules referred to their biological activity and size. The nitrogen loading rate (NLR) fed to the SBR was kept around 0.3g N(L day)(-1). The nitrite (limiting substrate) removal percentage was 98% during most of the operational period. The specific Anammox activity of the biomass was practically constant and around 0.4 g N(g VSSday)(-1) and the average feret diameter of the formed granules was 0.64 mm. Obtained results indicated that stirring speeds up to 180 rpm have no negative effect on the performance of the Anammox process, whereas Anammox activity decreased to 40% when a rotating speed of 250 rpm was tested and the average diameter decreased in 45%, the concentration of solids in the effluent increased to 0.2g TSSL(-1) and nitrite was accumulated in the reactor up to 60 mg NL(-1). 相似文献
997.
Two diterpene carboxylic acids, one a new kaurenoid derivative and one the previously characterized labdane, ()-cis-ozic acid, as well as a 相似文献
998.
Jeff A. O'Meara Christopher T. Lemke Cédrickx Godbout George Kukolj Lisette Lagacé Beno?t Moreau Diane Thibeault Peter W. White Montse Llinàs-Brunet 《The Journal of biological chemistry》2013,288(8):5673-5681
Although optimizing the resistance profile of an inhibitor can be challenging, it is potentially important for improving the long term effectiveness of antiviral therapy. This work describes our rational approach toward the identification of a macrocyclic acylsulfonamide that is a potent inhibitor of the NS3-NS4A proteases of all hepatitis C virus genotypes and of a panel of genotype 1-resistant variants. The enhanced potency of this compound versus variants D168V and R155K facilitated x-ray determination of the inhibitor-variant complexes. In turn, these structural studies revealed a complex molecular basis of resistance and rationalized how such compounds are able to circumvent these mechanisms. 相似文献
999.
1000.
Ekaterini Blaveri Fiona Kelly Alessandra Mallei Kriss Harris Adam Taylor Juliet Reid Maria Razzoli Lucia Carboni Chiara Piubelli Laura Musazzi Girogio Racagni Aleksander Mathé Maurizio Popoli Enrico Domenici Stewart Bates 《PloS one》2010,5(9)