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41.
Yogavel Manickam Nipun Malhotra Siddhartha Mishra Palak Babbar Abhishek Dusane Benoît Laleu Valeria Bellini Mohamed-Ali Hakimi Alexandre Bougdour Amit Sharma 《PLoS pathogens》2022,18(3)
Toxoplasmosis is caused by Toxoplasma gondii and in immunocompromised patients it may lead to seizures, encephalitis or death. The conserved enzyme prolyl-tRNA synthetase (PRS) is a validated druggable target in Toxoplasma gondii but the traditional ‘single target–single drug’ approach has its caveats. Here, we describe two potent inhibitors namely halofuginone (HFG) and a novel ATP mimetic (L95) that bind to Toxoplasma gondii PRS simultaneously at different neighbouring sites to cover all three of the enzyme substrate subsites. HFG and L95 act as one triple-site inhibitor in tandem and form an unusual ternary complex wherein HFG occupies the 3’-end of tRNA and the L-proline (L-pro) binding sites while L95 occupies the ATP pocket. These inhibitors exhibit nanomolar IC50 and EC50 values independently, and when given together reveal an additive mode of action in parasite inhibition assays. This work validates a novel approach and lays a structural framework for further drug development based on simultaneous targeting of multiple pockets to inhibit druggable proteins. 相似文献
42.
Amit Kumar Solanki Abhishek Acharya Himani Kaushik Bharti Bhatia Lalit C Garg 《Bioinformation》2021,17(6):628
Beta toxin from Clostridium perfringens after being secreted in gut is capable of causing necrotic enteritis in humans and several other animal species and does not respond to routinely used antibiotics. Therefore, there is a need to design an effective inhibitor for the Clostridium perfringens beta toxin (CPB) using cutting edge drug discovery technologies. Hence, potential CPB inhibitors were identified using computer aided screening of compounds from the ZINC database. Further, we document the molecular docking analysis of Clostridium perfringens beta toxin model (that revealed 4 binding pockets, A-D) with the identified potential inhibitors. We show that ZINC291192 [N-[(1-methylindol-3-yl) methyl eneamino]-7,10-dioxabicyclo[4.4.0]deca-2,4,11-triene-8- carboxamide] has optimal binding features with calculated binding energy of -10.38 kcal/mol and inhibition constant of 24.76 nM for further consideration. 相似文献
43.
44.
Genotyping over 100,000 SNPs on a pair of oligonucleotide arrays 总被引:1,自引:0,他引:1
Matsuzaki H Dong S Loi H Di X Liu G Hubbell E Law J Berntsen T Chadha M Hui H Yang G Kennedy GC Webster TA Cawley S Walsh PS Jones KW Fodor SP Mei R 《Nature methods》2004,1(2):109-111
We present a genotyping method for simultaneously scoring 116,204 SNPs using oligonucleotide arrays. At call rates >99%, reproducibility is >99.97% and accuracy, as measured by inheritance in trios and concordance with the HapMap Project, is >99.7%. Average intermarker distance is 23.6 kb, and 92% of the genome is within 100 kb of a SNP marker. Average heterozygosity is 0.30, with 105,511 SNPs having minor allele frequencies >5%. 相似文献
45.
Pseudomonas sp. NBRI 4014 is a potent phosphorus solubilizer (284 μg/ml). It also produced significant levels of siderophore (143.87
μg/ml) and IAA (5.6 μg/ml). Siderotyping indicated it was P. aeruginosa siderovar 1. Cadmium (180 μM), nickel (420 μM), and chromium (370 μM) resistant mutants were developed and characterized
for their PGPR properties. Mutants were stable under non-selective pressure. In cases of nickel and cadmium, there were reductions
of the siderophore levels. However, they were able to promote root and shoot elongation in soybeans (Glycine max PK 564) at a significant level (p < 0.05) in the presence of metals unfamiliar to the wild type. The persistence and stability of mutants were evident in rhizospheric
soil, thus their exploitation for polluted/contaminated sites was supported.
Received: 27 December 2001 / Accepted: 28 January 2002 相似文献
46.
Rubinder K Chadha BS Singh N Saini HS Singh S 《Journal of industrial microbiology & biotechnology》2002,29(2):70-74
Thermomyces lanuginosus was subjected to three cycles of mutagenesis (UV/NTG) and a selection procedure to develop amylase-hyperproducing, catabolite-repression-resistant
and partially constitutive strains. One of the selected derepressed mutant strain III51, produced ∼7- and 3-fold higher specific activity of α-amylase (190 U/mg protein) and glucoamylase (105 U/mg protein), respectively,
compared to a wild-type parental strain. Further, the effect of production parameters on mutant strain III51 was studied using a Box–Behnken design. The regression models computed showed significantly high R
2 values of 96 and 97% for α-amylase and glucoamylase activities, respectively, indicating that they are appropriate for predicting
relationships between corn flour, soybean meal and pH with α-amylase and glucoamylase production. Journal of Industrial Microbiology & Biotechnology (2002) 29, 70–74 doi:10.1038/sj.jim.7000270
Received 05 July 2001/ Accepted in revised form 16 April 2002 相似文献
47.
48.
Kaushalendra Kumar Ashish Singh Santosh Kumar Faujdar Ram Abhishek Singh Usha Ram Joel Negin Paul R. Kowal 《PloS one》2015,10(8)
Background and Objectives
The provision of affordable health care is generally considered a fundamental goal of a welfare state. In addition to its role in maintaining and improving the health status of individuals and households, it impacts the economic prosperity of a society through its positive effects on labor productivity. Given this context, this paper assesses socioeconomic-differentials in the impact of out-of-pocket-health-expenditure (OOPHE) on impoverishment in China and India, two of the fastest growing economies of the world.Data and Methods
The paper uses data from the World Health Organisation’s Study on Global Ageing and Adult Health (WHO SAGE), and Bivariate as well as Multivariate analyses for investigating the socioeconomic-differentials in the impact of out-of-pocket-health-expenditure (OOPHE) on impoverishment in China and India.Results and Conclusions
Annually, about 7% and 8% of the population in China and India, respectively, fall in poverty due to OOPHE. Also, the percentage shortfall in income for the population from poverty line due to OOPHE is 2% in China and 1.3% in India. Further, findings from the multivariate analysis indicate that lower wealth status and inpatient as well as outpatient care increase the odds of falling below poverty line significantly (with the extent much higher in the case of in-patient care) due to OOPHE in both China and India. In addition, having at least an under-5 child in the household, living in rural areas and having a household head with no formal education increases the odds of falling below poverty line significantly (compared to a head with college level education) due to OOPHE in China; whereas having at least an under-5 child, not having health insurance and residing in rural areas increases the odds of becoming poor significantly due to OOPHE in India. 相似文献49.
Influence of protein and carbohydrate contents of soy protein hydrolysates on cell density and IgG production in animal cell cultures 下载免费PDF全文
Abhishek J. Gupta Peter A. Wierenga Harry Gruppen Jan‐Willem Boots 《Biotechnology progress》2015,31(5):1396-1405
The variety of compounds present in chemically defined media as well as media supplements makes it difficult to use a mechanistic approach to study the effect of supplement composition on culture functionality. Typical supplements, such as soy protein hydrolysates contain peptides, amino acids, carbohydrates, isoflavones, and saponins. To study the relative contribution of these compound classes, a set of hydrolysates were produced, containing 58‐83% proteinaceous material and 5‐21% carbohydrates. While the content of the different compounds classes varied, the composition (e.g., peptide profiles, carbohydrate composition) did not vary in hydrolysates. The hydrolysates were supplemented to a chemically defined medium in cell culture, based on equal weight and on equal protein levels. The latter showed that an increase in the carbohydrate concentration significantly (P value < 0.004) increased integral viable cell density (IVCD) (R = 0.7) and decreased total IgG (R = ?0.7) and specific IgG production (R = ?0.9). The extrapolation of effects of protein concentration showed that an increase in protein concentration increased total and specific IgG production and suppressed IVCD. In addition to proteins and carbohydrates, the functionality of soy protein hydrolysates may be modulated by the presence of other minor compounds. In the current study, the large differences in the balance between total proteins and total carbohydrates in the supplemented media seem to be a main factor influencing the balance between the viable cell density, total IgG, and specific IgG production. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1396–1405, 2015 相似文献
50.
Abhishek Kumar Sandeep J. Sarde Anita Bhandari 《Biochemical and biophysical research communications》2014
Angiotensinogen (AGT) belongs to the serpin superfamily. It acts as the unique substrate of all angiotensin peptides, which generates a spectrum of angiotensin peptides in the renin-angiotensin system and regulates hypertension. This serpin belongs to the multiple member group V2 of the intron encoded vertebrate serpin classification. Despite huge advancements in the understanding of angiotensinogen based on biochemical properties and its roles in the RAS, phylogenetic history of AGT remains forgotten. To date, there is no comprehensive study illustrating the phylogenetic history of AGT. Herein, we investigated phylogenetic traits of AGT gene across vertebrates. Gene structures of AGT gene from selected ray-finned fishes varied in exon I and II with insertions of two novel introns in the core domain for ray-finned fishes at the position 77c and 233c. We that found AGT loci is conserved from lampreys to human and estimated to be older than 500 MY. By comparing AGT protein in 57 vertebrate genomes, we illustrated that the reactive center loop (RCL) of AGT protein became from inhibitory (in lampreys, GTEAKAETVVGIMPI†SMPPT) to non-inhibitory (in human, EREPTESTQQLNKPE†VLEVT) during period of 500 MY. We identified 690 AGT variants by analysis of 1092 human genomes with top three variation classes belongs to SNPs (89.7%), somatic SNVs (5.2%) and deletion (2.9%). There are 32 key residues out of 121 missense variants, which are deleterious for AGT protein, computed by combination of SIFT and PolyPhen V2 methods. These results may have clinical implications for understanding hypertension. 相似文献