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991.
MOTIVATION: All residues in a protein are not equally important. Some are essential for the proper structure and function of the protein, whereas others can be readily replaced. Conservation analysis is one of the most widely used methods for predicting these functionally important residues in protein sequences. RESULTS: We introduce an information-theoretic approach for estimating sequence conservation based on Jensen-Shannon divergence. We also develop a general heuristic that considers the estimated conservation of sequentially neighboring sites. In large-scale testing, we demonstrate that our combined approach outperforms previous conservation-based measures in identifying functionally important residues; in particular, it is significantly better than the commonly used Shannon entropy measure. We find that considering conservation at sequential neighbors improves the performance of all methods tested. Our analysis also reveals that many existing methods that attempt to incorporate the relationships between amino acids do not lead to better identification of functionally important sites. Finally, we find that while conservation is highly predictive in identifying catalytic sites and residues near bound ligands, it is much less effective in identifying residues in protein-protein interfaces. AVAILABILITY: Data sets and code for all conservation measures evaluated are available at http://compbio.cs.princeton.edu/conservation/ 相似文献
992.
A variety of tropane derivatives 14a–g were prepared via the reaction of the alcohol analogs 12a and 12b with substituted fluorobenzenes 13a–f. The prepared compounds were tested for their activity and selectivity toward the norepinephrine transporter (NET) and serotonin transporter (SERT) using yohimbine-induced mortality and 5-hydroxytryptophan-induced neurotoxicity in mice, respectively. All the tested compounds were found to be NE and 5-HT reuptake inhibitors except 14d which exhibited selective 5-HT reuptake inhibition activity. 相似文献
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Forouzan Amerizadeh Afsane Bahrami Majid Khazaei AmirReza Hesari Majid Rezayi Sahar Talebian Mona Maftouh Mehrdad Moetamani-Ahmadi Sima Seifi Soodabeh Shahidsales Mona Joudi-Mashhad Gordon A. Ferns Faezeh Ghasemi Amir Avan 《Journal of cellular biochemistry》2019,120(5):6962-6971
The transforming growth factor-β (TGF-β) signaling pathway is one of the important pathways involved in the cancer cell proliferation, invasion, migration, angiogenesis, apoptosis, as well as in metastasis by agitation or invasion of metastasis-related factors, including matrix metalloproteinase (MMP), epithelial-to-mesenchymal transition (EMT), tumor microenvironment (TME), cancer stem cells (CSCs), and cell adhesion molecules (CAMs). These data suggest its potential value as a therapeutic object in the treatment of malignancies including breast cancer. Several pharmacological approaches have been established to suppress TGF-β pathway; such as vaccines, small molecular inhibitors, antisense oligonucleotides, and monoclonal antibodies. Some of these are now approved by the US Food and Drug Administration for targeting the TGF-β signaling pathway. This study attempts to summarize the current data about the functions of TGF-β in cancer cells, and their probable application in the cancer therapy with a specific emphasis on recent preclinical and clinical research in the treatment of breast cancer and its prognostic value. 相似文献
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In situ analysis of sulfur species in sulfur globules produced from thiosulfate by Thermoanaerobacter sulfurigignens and Thermoanaerobacterium thermosulfurigenes 下载免费PDF全文
Lee YJ Prange A Lichtenberg H Rohde M Dashti M Wiegel J 《Journal of bacteriology》2007,189(20):7525-7529
The Firmicutes Thermoanaerobacter sulfurigignens and Thermoanaerobacterium thermosulfurigenes convert thiosulfate, forming sulfur globules inside and outside cells. X-ray absorption near-edge structure analysis revealed that the sulfur consisted mainly of sulfur chains with organic end groups similar to sulfur formed in purple sulfur bacteria, suggesting the possibility that the process of sulfur globule formation by bacteria is an ancient feature. 相似文献
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999.
Farahani Masoumeh Rezaei-Tavirani Mostafa Zali Alireza Zamanian-Azodi Mona 《Cellular and molecular neurobiology》2022,42(4):1091-1103
Cellular and Molecular Neurobiology - Autism spectrum disorder (ASD), a heterogeneous neurodevelopmental disorder resulting from both genetic and environmental risk factors, is manifested by... 相似文献
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Hesse Julia Rosse Mona K. Steckel Bodo Blank-Landeshammer Bernhard Idel Svenja Reinders Yvonne Sickmann Albert Sträter Norbert Schrader Jürgen 《Purinergic signalling》2022,18(1):115-121
Purinergic Signalling - CD73-derived adenosine plays a major role in damage-induced tissue responses by inhibiting inflammation. Damage-associated stimuli, such as hypoxia and mechanical stress,... 相似文献