排序方式: 共有61条查询结果,搜索用时 15 毫秒
41.
Mattias D. Hansson Tobias Karlberg Christopher A. G. Söderberg Sreekanth Rajan Martin J. Warren Salam Al-Karadaghi Stephen E. J. Rigby Mats Hansson 《Journal of biological inorganic chemistry》2011,16(2):235-242
Ferrochelatase catalyzes the insertion of Fe2+ into protoporphyrin IX. The enzymatic product heme (protoheme IX) is a well-known cofactor in a wide range of proteins. The
insertion of metal ions other than Fe2+ occurs rarely in vivo, but all ferrochelatases that have been studied can insert Zn2+ at a good rate in vitro. Co2+, but not Cu2+, is known to be a good substrate of the mammalian and Saccharomyces cerevisiae ferrochelatases. In contrast, Cu2+, but not Co2+, has been found to be a good substrate of bacterial Bacillus subtilis ferrochelatase. It is not known how ferrochelatase discriminates between different metal ion substrates. Structural analysis
of B. subtilis ferrochelatase has shown that Tyr13 is an indirect ligand of Fe2+ and a direct ligand of a copper mesoporphyrin product. A structure-based comparison revealed that Tyr13 aligns with a Met
residue in the S. cerevisiae and human ferrochelatases. Tyr13 was changed to Met in the B. subtilis enzyme by site-directed mutagenesis. Enzymatic measurements showed that the modified enzyme inserted Co2+ at a higher rate than the wild-type B. subtilis ferrochelatase, but it had lost the ability to use Cu2+ as a substrate. Thus, the B. subtilis Tyr13Met ferrochelatase showed the same metal specificity as that of the ferrochelatases from S. cerevisiae and human. 相似文献
42.
Sowmya Vanguru Lavanya Jilla Yasodakrishna Sajja Rajashaker Bantu Lingaiah Nagarapu Jagadeesh Babu Nanubolu Bala Bhaskar Nishant Jain Sreekanth Sivan Vijjulatha Manga 《Bioorganic & medicinal chemistry letters》2017,27(4):792-796
A new series of 1-((9-chloro-2,3-dimethyl-6,7-dihydro-5H-benzo[7]annulen-8-yl)methoxy)-3-(4-phenylpiperzin-1-yl) propan-2-ols (6a-k) have been designed, synthesized and their structures were established by spectroscopic data (FT-IR, 1H NMR, 13C NMR, HRMS) and further confirmed by X-ray analysis. The newly synthesized compounds 6a-k were evaluated for their in vitro anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MDA-MB-231 (breast), A549 (lung) and MIAPACA (pancreatic). Among the compounds tested, the compound 6e displayed most potent activity against four cancer cell lines with GI50 values ranging from 0.010 to 0.097 μM. The structure and anti-proliferative activity relationship was further supported by in silico molecular docking study of the active compounds against Colchicine binding site of β-tubulin. 相似文献
43.
Nervous systems extract and process information from the environment to alter animal behavior and physiology. Despite progress in understanding how different stimuli are represented by changes in neuronal activity, less is known about how they affect broader neural network properties. We developed a framework for using graph-theoretic features of neural network activity to predict ecologically relevant stimulus properties, in particular stimulus identity. We used the transparent nematode, Caenorhabditis elegans, with its small nervous system to define neural network features associated with various chemosensory stimuli. We first immobilized animals using a microfluidic device and exposed their noses to chemical stimuli while monitoring changes in neural activity of more than 50 neurons in the head region. We found that graph-theoretic features, which capture patterns of interactions between neurons, are modulated by stimulus identity. Further, we show that a simple machine learning classifier trained using graph-theoretic features alone, or in combination with neural activity features, can accurately predict salt stimulus. Moreover, by focusing on putative causal interactions between neurons, the graph-theoretic features were almost twice as predictive as the neural activity features. These results reveal that stimulus identity modulates the broad, network-level organization of the nervous system, and that graph theory can be used to characterize these changes. 相似文献
44.
Bava SV Sreekanth CN Thulasidasan AK Anto NP Cheriyan VT Puliyappadamba VT Menon SG Ravichandran SD Anto RJ 《The international journal of biochemistry & cell biology》2011,43(3):331-341
Paclitaxel is the most promising chemotherapeutic agent of plant origin despite its high cost and dose-limiting toxicity. Our earlier report has shown that cervical cancer cells can be sensitized by curcumin to paclitaxel-induced apoptosis through down-regulation of NF-κB and Akt. In the present study we have attempted to decipher the signaling pathways regulating the synergism of paclitaxel and curcumin. The study has clearly proved that Akt and NF-κB function successively in the sequence of paclitaxel induced signaling events where Akt is upstream of NF-κB. While inhibition of NF-κB led to complete inhibition of the synergism of paclitaxel and curcumin, inhibition of Akt brought about only partial reduction of the same, suggesting that, apart from Akt, there are other pathways induced by paclitaxel leading to NF-κB activation, which are also down-regulated by curcumin. Inactivation of NF-κB did not affect the activation of Akt and survivin, while that of Akt significantly inhibited NF-κB and completely inhibited up-regulation of survivin. Up-regulation of Cyclin-D1, Cox-2, XIAP and cIAP1 and phosphorylation of MAPKs, were completely inhibited on inactivation of NF-κB assigning a key regulatory role to NF-κB in the synergistic effect of paclitaxel and curcumin. While up-regulation of survivin by paclitaxel is regulated by Akt, independent of NF-κB, inactivation of neither Akt nor NF-κB produced any change in Bcl-2 level suggesting a distinct pathway for its action. As curcumin could effectively down-regulate all these survival signals induced by paclitaxel, we suggest it as a potent chemosensitizer to improve the therapeutic index of paclitaxel. 相似文献
45.
Sreekanth Ramachandran Manoranjan Panda Kakoli Mukherjee Nilanjana Roy Choudhury Subramanyam J. Tantry Chaitanya Kumar Kedari Vasanthi Ramachandran Sreevalli Sharma V.K. Ramya Supreeth Guptha Vasan K. Sambandamurthy 《Bioorganic & medicinal chemistry letters》2013,23(17):4996-5001
Imidazo[1,2-a]pyridine-8-carboxamides as a novel antimycobacterial lead were generated by whole cell screening of a focused library against Mycobacterium tuberculosis. Herein, we describe the synthesis and structure activity relationship evaluation of this class of inhibitors and the optimization of physicochemical properties. These are selective inhibitors of Mycobacterium tuberculosis with no activity on either gram positive or gram negative pathogens. 相似文献
46.
Good use of fruit wastes: eco‐friendly synthesis of silver nanoparticles,characterization, BSA protein binding studies 下载免费PDF全文
T. V. M. Sreekanth Sambandam Ravikumar Yong Rok Lee 《Journal of molecular recognition : JMR》2016,29(6):253-259
A simple and eco‐friendly methodology for the green synthesis of silver nanoparticles (AgNPs) using a mango seed extract was evaluated. The AgNPs were characterized by ultraviolet‐visible spectrophotometry, Fourier transform infrared spectroscopy, transmission electron microscopy, energy dispersive X‐ray spectroscopy, and X‐ray diffraction. The interaction between the green synthesized AgNPs and bovine serum albumin (BSA) in an aqueous solution at physiological pH was examined by fluorescence spectroscopy. The results confirmed that the AgNPs quenched the fluorophore of BSA by forming a ground state complex in aqueous solution. This fluorescence quenching data were also used to determine the binding sites and binding constants at different temperatures. The calculated thermodynamic parameters (ΔG°, ΔH° and ΔS°) suggest that the binding process occurs spontaneously through the involvement of electrostatic interactions. The synchronous fluorescence spectra showed a blue shift, indicating increasing hydrophobicity. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
47.
Ajit Prakash Sreekanth Rajan Ho Sup Yoon 《Protein science : a publication of the Protein Society》2016,25(4):905-910
Human FKBP25 (hFKBP25) is a nuclear immunophilin and interacts with several nuclear proteins, hence involving in many nuclear events. Similar to other FKBPs, FK506 binding domain (FKBD) of hFKBP25 also binds to immunosuppressive drugs such as rapamycin and FK506, albeit with a lower affinity for the latter. The molecular basis underlying this difference in affinity could not be addressed due to the lack of the crystal structure of hFKBD25 in complex with FK506. Here, we report the crystal structure of hFKBD25 in complex with FK506 determined at 1.8 Å resolution and its comparison with the hFKBD25–rapamycin complex, bringing out the microheterogeneity in the mode of interaction of these drugs, which could possibly explain the lower affinity for FK506. 相似文献
48.
Karki SS Thota S Darj SY Balzarini J De Clercq E 《Bioorganic & medicinal chemistry》2007,15(21):6632-6641
The synthesis and characterization of ruthenium compounds (Ru1-Ru12) of the type [Ru(S)(2)(K)], (where S=1,10-phenanthroline/2,2'-bipyridine and K=itsz, MeO-btsz, 4-Cl-btsz, 2-Cl-btsz, 2-F-btsz, hfc and itsz=isatin-3-thiosemicarbazone, MeO-btsz=1-(4'-methoxy-benzyl)-thiosemicarbazone, hfc=2-{[3-chloro-4-fluoro-phenylimino]methyl}phenol, 4-Cl-btsz=1-(4'-chlorobenzyl)-thiosemicarbazone, 2-Cl-btsz=1-(2'-chloro benzyl)-thiosemicarbazone, 2-F-btsz=1-(2'-fluorobenzyl)-thiosemicarbazone) are described. These ligands form bidentate octahedral ruthenium compounds. The title compounds were subjected to in vivo anticancer activity against a transplantable murine tumor cell line Ehrlich's Ascites Carcinoma (EAC) and in vitro cytotoxic activity against human cancer cell line Molt 4/C8, CEM and murine tumor cell line L1210. Ruthenium compounds (Ru1-Ru12) showed promising biological activity especially in decreasing tumor volume and viable ascites cell counts. Treatment with these compounds prolonged the life span of mice bearing EAC tumor by 10-43%. In vitro evaluation of these ruthenium compounds revealed cytotoxic activity from 0.24 to 27 microM against Molt 4/C8, 0.27 to 48 microM against CEM, and 0.94 to 248 microM against L1210. Their ligands alone failed to show cytotoxic activity at the concentrations tested (68-405 microM). 相似文献
49.
Nadim S. Shaikh Jitesh P. Iyer Yogesh S. Munot Partha P. Mukhopadhyay Amol A. Raje Ranganayaki Nagaraj Vijay Jamdar Ravindra Gavhane Mahendra Lohote Prasad Sherkar Madhu Bala Rajkanth Petla Ashwinkumar Meru Dhananjay Umrani Sreekanth Rouduri Sachin Joshi Satyanarayan Reddy Vishwottam Kandikere Kasim A. Mookhtiar 《Bioorganic & medicinal chemistry letters》2019,29(16):2208-2217
Targeting nuclear receptor RORγ is recognized to be beneficial in multiple autoimmune disorders. We disclosed new indole analogues as potent RORγ inverse agonists. RO-2 as one of the potent and orally bioavailable compounds was evaluated in various models of autoimmune disorder. It showed potent suppression of downstream markers of RORγt activity in murine and human primary cells, ex vivo PD assay and in multiple animal models of autoimmune diseases. The results indicate the potential of these indole analogues as orally bioavailable small molecule inverse agonists of RORγt, efficacious in various Th17 driven models of autoimmune disorders. 相似文献
50.
Bh3 induced conformational changes in Bcl‐Xl revealed by crystal structure and comparative analysis 下载免费PDF全文
Apoptosis or programmed cell death is a regulatory process in cells in response to stimuli perturbing physiological conditions. The Bcl‐2 family of proteins plays an important role in regulating homeostasis during apoptosis. In the process, the molecular interactions among the three members of this family, the pro‐apoptotic, anti‐apoptotic and BH3‐only proteins at the mitochondrial outer membrane define the fate of a cell. Here, we report the crystal structures of the human anti‐apoptotic protein Bcl‐XL in complex with BH3‐only BIDBH3 and BIMBH3 peptides determined at 2.0 Å and 1.5 Å resolution, respectively. The BH3 peptides bind to the canonical hydrophobic pocket in Bcl‐XL and adopt an alpha helical conformation in the bound form. Despite a similar structural fold, a comparison with other BH3 complexes revealed structural differences due to their sequence variations. In the Bcl‐XL‐BIDBH3 complex we observed a large pocket, in comparison with other BH3 complexes, lined by residues from helices α1, α2, α3, and α5 located adjacent to the canonical hydrophobic pocket. These results suggest that there are differences in the mode of interactions by the BH3 peptides that may translate into functional differences in apoptotic regulation. Proteins 2015; 83:1262–1272. © 2015 Wiley Periodicals, Inc. 相似文献