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1.
A fraction with the ability to bind the terminal fragment of equine adenovirus (EAd) DNA was prepared from MDBK cell nuclei. The fraction (MDBK nuclear factor) bound to the terminal fragment of all human and animal adenovirus DNAs examined except avian adenovirus EDS-76. However, the terminal fragments of two animal adenoviruses, EAd and bovine adenovirus type 3 (BAd3), showed higher affinity for the nuclear factor than the others. The MDBK nuclear factor-binding site determined by footprinting analysis was the sequence located between nucleotides 22 and 46 in EAd, between 36 and 53 in canine adenovirus type 2, and between 20 and 46 in BAd3, counting from the terminus. The respective binding site contained a sequence resembling the consensus sequence. The binding site of Ad4 DNA was not within the inverted terminal repetition, but was located at least 550 base pairs apart from the terminus. 相似文献
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Parasuraman Aiya Subramani Venkata Ramireddy Narala R Dinakaran Michael Dakshayani Lomada Madhava C Reddy 《Bioinformation》2015,11(5):248-253
Protein prenylation is a posttranslational modification that is indispensable for translocation of membrane GTPases like Ras, Rho,
Ras etc. Proteins of Ras family undergo farnesylation by FTase while Rho family goes through geranylgeranylation by GGTase1.
There is only an infinitesimal difference in signal recognition between FTase and GGTase1. FTase inhibitors mostly end up
selecting the cells with mutated Ras proteins that have acquired affinity towards GGTase1 in cancer microcosms. Therefore, it is of
interest to identify GGTase1 and FTase dual inhibitors using the docking tool AutoDock Vina. Docking data show that curcumin
(from turmeric) has higher binding affinity to GGTase1 than that of established peptidomimetic GGTase1 inhibitors (GGTI) such as
GGTI-297, GGTI-298, CHEMBL525185. Curcumin also interacts with FTase with binding energy comparable to co-crystalized
compound 2-[3-(3-ethyl-1-methyl-2-oxo-azepan-3-yl)-phenoxy]-4-[1-amino-1-(1-methyl-1h-imidizol-5-yl)-ethyl]-benzonitrile (BNE).
The docked complex was further simulated for 10 ns using molecular dynamics simulation for stability. Thus, the molecular basis
for curcumin binding to GGTase1 and FTase is reported. 相似文献
4.
Adenovirus DNA polymerase (AdPol) contains three clusters of basic amino acids within the N-terminal 48 amino acids: RARR, which begins at amino acid 8, RRRVR, which begins at amino acid 25, and RARRRR, which begins at amino acid 41. These clusters are designated BS I, BS II, and BS III, respectively. (The amino acid codes are: R, arginine; A, alanine; V, valine.) Mutational analysis of these noncontiguous clusters showed that AdPol contains a novel organization of bipartite nuclear localization signals (NLS) that interact differentially to serve in the nuclear targeting of AdPol or of chimeric proteins in which AdPol is linked to Escherichia coli beta-galactosidase (beta-gal). The region containing BS I and BS II functioned interdependently as an NLS for the nuclear targeting of AdPol, for which BS III was dispensible. However, the region containing BS II and BS III constituted a second and more efficient bipartite NLS for the nuclear targeting of the AdPol-E. coli beta-gal fusion protein. Moreover, deletion or limited insertion of amino acids in the spacer region between BS II and BS III did not affect their nuclear targeting function for these fusion proteins. Chou-Fasman predictive analysis of protein secondary structure in the vicinity of the bipartite NLS sequences supports a model in which protein conformation in the spacer region may play an important role in bringing these clusters of basic amino acids into close proximity, allowing them to function as nuclear targeting signals for this class of nuclear proteins. 相似文献
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For comparison with earlier data on naturally occurring non-polar amino acids (Ala, Leu, Phe, Val, Ile), the comparative helix-forming tendencies have been measured for non-polar amino acid residues that have unbranched side-chains, with an ethyl, propyl or butyl group, and also for methionine. The substitutions are made in a 17-residue alanine-based peptide. The results show that straight-chain non-polar amino acids have high helix-forming tendencies compared to beta-branched non-polar amino acids. Restriction of side-chain conformations in the helix, with a corresponding reduction in conformational entropy, is the likely explanation. There is a small increase in helix-forming tendency as the side-chain increases in length from ethyl to butyl, which suggests that a helix-stabilizing hydrophobic interaction is being detected. 相似文献
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Seetharamaiyer Padmanabhan Ruth C. Lavin Paresh M. Thakker Jinqing Guo Lu Zhang Deke Moore Michael E. Perlman Cassandra Kirk Deborah Daly Kathy J. Burke-Howie Teresa Wolcott Suchitra Chari David Berlove James B. Fischer William F. Holt Graham J. Durant Robert N. McBurney 《Bioorganic & medicinal chemistry letters》2001,11(24):1945-3155
Solution-phase synthesis of various acylguanidine derivatives and the evaluation of a small library of compounds as potential sodium channel blockers are described. 相似文献
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Huiguo Lai Dengfeng Dou Sridhar Aravapalli Tadahisa Teramoto Gerald H. Lushington Tom M. Mwania Kevin R. Alliston David M. Eichhorn Radhakrishnan Padmanabhan William C. Groutas 《Bioorganic & medicinal chemistry》2013,21(1):102-113
1,2-Benzisothiazol-3(2H)-ones and 1,3,4-oxadiazoles individually have recently attracted considerable interest in drug discovery, including as antibacterial and antifungal agents. In this study, a series of functionalized 1,2-benzisothiazol-3(2H)-one—1,3,4-oxadiazole hybrid derivatives were synthesized and subsequently screened against Dengue and West Nile virus proteases. Ten out of twenty-four compounds showed greater than 50% inhibition against DENV2 and WNV proteases ([I] = 10 μM). The IC50 values of compound 7n against DENV2 and WNV NS2B/NS3 were found to be 3.75 ± 0.06 and 4.22 ± 0.07 μM, respectively. The kinetics data support a competitive mode of inhibition by compound 7n. Molecular modeling studies were performed to delineate the putative binding mode of this series of compounds. This study reveals that the hybrid series arising from the linking of the two scaffolds provides a suitable platform for conducting a hit-to-lead optimization campaign via iterative structure–activity relationship studies, in vitro screening and X-ray crystallography. 相似文献