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211.
Samikshan Dutta Jyothi Shaw Swagata Sinha Kanchan Mukhopadhyay 《Indian journal of human genetics》2009,15(1):28-31
Chromosomal abnormalities are thought to be the most common cause of mental retardation (MR). However, apart from a few selected types with typical aneuploidy, like Downs syndrome, Klinefelter syndrome, Turner syndrome, etc., the frequency of detectable chromosomal abnormalities in association with idiopathic MR is very low. In this study, we have investigated chromosomal abnormalities in female MR subjects (n = 150) by high-resolution GTG banding. Of them, 30 cases were diagnosed as Downs syndrome. Among the remaining (n = 120), chromosomal abnormalities/marked polymorphisms were detectable in only three MR cases (0.025). 相似文献
212.
Nikhil Jain Abu Rafay Khan Sushil Kumar Tomar Dipak Dutta Balaji Prakash 《Biochemical and biophysical research communications》2009,379(2):201-205
HflX is a GTP binding protein of unknown function. Based on the presence of the hflX gene in hflA operon, HflX was believed to be involved in the lytic-lysogenic decision during phage infection in Escherichia coli. We find that E. coli HflX binds 16S and 23S rRNA - the RNA components of 30S and 50S ribosomal subunits. Here, using purified ribosomal subunits, we show that HflX specifically interacts with the 50S. This finding is in line with the homology of HflX to GTPases involved in ribosome biogenesis. However, HflX-50S interaction is not limited to a specific nucleotide-bound state of the protein, and the presence of any of the nucleotides GTP/GDP/ATP/ADP is sufficient. In this respect, HflX is different from other GTPases. While E. coli HflX binds and hydrolyses both ATP and GTP, only the GTP hydrolysis activity is stimulated by 50S binding. This work uncovers interesting attributes of HflX in ribosome binding. 相似文献
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Mukherjee M Dutta K White MA Cowburn D Fox RO 《Protein science : a publication of the Protein Society》2006,15(6):1342-1355
Flaviviruses cause many human diseases, including dengue fever, yellow fever, West Nile viral encephalitis, and hemorrhagic fevers, and are transmitted to their vertebrate hosts by infected mosquitoes and ticks. Domain III of the envelope protein (E-D3) is considered to be the primary viral determinant involved in the virus-host-cell receptor interaction, and thus represents an excellent target for antiviral drug development. Langat (LGT) virus is a naturally attenuated BSL-2 TBE virus and is a model for the pathogenic BSL-3 and BSL-4 viruses in the serogroup. We have determined the solution structure of LGT-E-D3 using heteronuclear NMR spectroscopy. The backbone dynamics of LGT-E-D3 have been investigated using 15N relaxation measurements. A detailed analysis of the solution structure and dynamics of LGT-E-D3 suggests potential residues that could form a surface for molecular recognition, and thereby represent a target site for antiviral therapeutics design. 相似文献
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Background
Novel therapeutics are urgently needed to control tuberculosis (TB). Thioridazine (THZ) is a candidate for the therapy of multidrug and extensively drug-resistant TB.Methodology/Principal Findings
We studied the impact of THZ on Mycobacterium tuberculosis (Mtb) by analyzing gene expression profiles after treatment at the minimal inhibitory (1x MIC) or highly inhibitory (4x MIC) concentrations between 1–6 hours. THZ modulated the expression of genes encoding membrane proteins, efflux pumps, oxido-reductases and enzymes involved in fatty acid metabolism and aerobic respiration. The Rv3160c-Rv3161c operon, a multi-drug transporter and the Rv3614c/3615c/3616c regulon, were highly induced in response to THZ. A significantly high number of Mtb genes co-expressed with σB (the σB regulon) was turned on by THZ treatment. σB has recently been shown to protect Mtb from envelope-damage. We hypothesized that THZ damages the Mtb cell-envelope, turning on the expression of the σB regulon. Consistent with this hypothesis, we present electron-microscopy data which shows that THZ modulates cell-envelope integrity. Moreover, the Mtb mutants in σH and σE, two alternate stress response sigma factors that induce the expression of σB, exhibited higher sensitivity to THZ, indicating that the presence and expression of σB allows Mtb to resist the impact of THZ. Conditional induction of σB levels increased the survival of Mtb in the presence of THZ.Conclusions/Significance
THZ targets different pathways and can thus be used as a multi-target inhibitor itself as well as provide strategies for multi-target drug development for combination chemotherapy. Our results show that the Mtb sigma factor network comprising of σH, σE and σB plays a crucial role in protecting the pathogen against cell-envelope damage. 相似文献220.