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71.
Predicting the impact of mutations on the specific activity of Bacillus thermocatenulatus lipase using a combined approach of docking and molecular dynamics 下载免费PDF全文
Onur Yukselen Emel Timucin Ugur Sezerman 《Journal of molecular recognition : JMR》2016,29(10):466-475
Lipases are important biocatalysts owing to their ability to catalyze diverse reactions with exceptional substrate specificities. A combined docking and molecular dynamics (MD) approach was applied to study the chain‐length selectivity of Bacillus thermocatenulatus lipase (BTL2) towards its natural substrates (triacylglycerols). A scoring function including electrostatic, van der Waals (vdW) and desolvation energies along with conformational entropy was developed to predict the impact of mutation. The native BTL2 and its 6 mutants (F17A, V175A, V175F, D176F, T178V and I320F) were experimentally analyzed to determine their specific activities towards tributyrin (C4) or tricaprylin (C8), which were used to test our approach. Our scoring methodology predicted the chain‐length selectivity of BTL2 with 85.7% (6/7) accuracy with a positive correlation between the calculated scores and the experimental activity values (r = 0.82, p = 0.0004). Additionally, the impact of mutation on activity was predicted with 75% (9/12) accuracy. The described study represents a fast and reliable approach to accurately predict the effect of mutations on the activity and selectivity of lipases and also of other enzymes. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
72.
GhoshMoulick R Bhattacharya J Roy S Basak S Dasgupta AK 《Biochimica et biophysica acta》2007,1774(2):233-242
Glycation, a local covalent interaction, leads to alterations in secondary and tertiary structures of hemoglobin, the changes produced by fructose being more pronounced than those caused by glucose. The Stokes diameter of hemoglobin increases upon glycation from 7 to 14 nm and a concurrent inter-chain cross-linking and heme loss are also observed, particularly in the later stage of glycation. An initial increase of tryptophan (trp) fluorescence was observed in both glucation and fructation. In case of frucation however there was a decrease in tryptophan fluorescence that was accompanied by an increase in fluorescence of the advanced glycosylation end products (AGEs). This fluorescence behavior is indicative of energy transfer between tryptophan and the AGEs formed during the late stage of glycation. Emergence of an isosbestic point in the fluorescence spectra (taken at different time intervals) implies existence of two distinct glycation stages. The late glycation stage is also marked by an increase of beta structure and random coil at the expense of alpha helix. It is further observed that this compensatory loss of alpha helix (reported for the first time) and increase in beta sheet and random coil elements depend on the number of solvent-accessible glycation sites (rather than total number of such sites) and the subunit assembly of the protein. 相似文献
73.
Emel Rothzerg Jiake Xu David Wood Sulev Kks 《Experimental biology and medicine (Maywood, N.J.)》2021,246(19):2072
The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) project aims to determine molecular changes that drive childhood cancers, including osteosarcoma. The main purpose of the program is to use the open-source database to develop novel, effective, and less toxic therapies. We downloaded TARGET-OS RNA-Sequencing data through R studio and merged the mRNA expression of genes with clinical information (vital status, survival time and gender). Further, we analyzed differential gene expressions between dead and alive patients based on TARGET-OS project. By this study, we found 5758 differentially expressed genes between deceased and alive patients with a false discovery rate below 0.05; 4469 genes were upregulated in deceased patients compared to alive, whereas 1289 genes were downregulated. The survival-related genes were obtained using Kaplan–Meier survival analysis and Cox univariate regression (KM < 0.05 and Cox P-value < 0.05). Out of 5758 differentially expressed genes, only 217 have been associated with overall survival. Eight survival-related downregulated genes (ERCC4, CLUAP1, CTNNBIP1, GCA, RAB40C, SIRPA, USP11, and TCN2) and four survival-related upregulated genes (MUC1, COL13A1, JAG2 and KAZALD1) were selected for further analysis as potential independent prognostic candidate genes. This study may help to discover novel prognostic markers and potential therapeutic targets for osteosarcoma. 相似文献
74.
The relationship between trace elements and cardiac markers in acute coronary syndromes 总被引:3,自引:0,他引:3
Emel Altekin Canan oker Ali Rza iman Banu
nvural Filiz Kuralay
nder Krml 《Journal of trace elements in medicine and biology》2005,18(3):235-242
Previous studies have demonstrated increased serum copper and iron levels and decreased selenium and zinc levels in patients with myocardial infarction. Furthermore, the prognostic value of the levels of trace elements in myocardial infarction has been stressed. We examined serum levels of Cu, Fe, Zn and Se, as well as glutathione peroxidase (GPx), a selenoenzyme with antioxidant properties, and C-reactive protein (CRP), a marker of inflammation, in acute coronary syndromes (ACS) regarding their relationship to cardiac troponins and creatine kinase-MB mass (CK-MBm), important prognostic markers. Serum trace elements, GPx activity and CRP were determined in 70 patients with ACS who were admitted within 12 h after the onset. Differences in these parameters were evaluated in three groups of patients divided according to the levels of cardiac markers: group III consisted of patients with high increases in cTnT, cTnI and CK-MBm (> or =0.9 ng/mL, > or =1.0 ng/mL, > or =30 ng/mL, respectively), patients with milder increases in these markers were included in groups II and I consisted of patients with values just above the upper reference limits. Serum Fe levels increased significantly in group II and even more prominently in group III compared to group I (p = 0.04, 0.002, respectively). There was no significant difference between groups II and III. The increase in serum Cu was significant in group III compared to both groups II and I (p = 0.04, 0.001, respectively). There was no significant difference between groups I and II regarding Cu and Zn. The decrease in serum Se and GPx levels was significant only between groups III and I (p = 0.004 for Se and p = 0.0001 for GPx). CRP levels showed a significant increase in group III compared to groups II and I (p = 0.03 and 0.001). CRP showed a significant positive and GPx a significant negative correlation to the cardiac markers cTnT, cTnI and CK-MBm. Cu was positively correlated to all cardiac markers, while the positive correlation between Fe and cardiac markers was significant only for cTnI. Both Zn and Se were negatively correlated to cTnT, and Se was also to cTnI. In conclusion, the increase in serum levels of Cu and Fe and the decrease in serum levels of Zn and Se in patients with higher levels of troponins and CK-MBm imply that trace element levels are related to the degree of myocardial damage and thus may play a role in the pathogenesis of ischemic heart disease. The strong correlations between cardiac markers and both CRP and GPx suggest that these parameters are promising prognostic factors in acute coronary syndromes. 相似文献
75.
Sambuddha Banerjee Soma Sen Subhra Basak Samiran Mitra David L. Hughes Cédric Desplanches 《Inorganica chimica acta》2008,361(9-10):2707-2714
Two new pseudohalide-bridged copper(II) complexes [{Cu(PBH)(μ1,1-CNO)}2] (1) and {Cu(PBH)(μ1,5-NCNCN)}n (2) (where HPBH = 2-pyridinecarboxaldehyde benzoyl hydrazone) have been synthesised and characterised by elemental analysis, CV, IR and UV–Vis spectral studies. The tridentate hydrazone pro-ligand (HPBH) was obtained by the condensation of benzhydrazide and pyridine-2-carboxaldehyde. Structures of both complexes have been established by X-ray crystallography which shows that 1 is a μ1,1-CNO?-bridged dimer whereas 2 is a μ1,5-dca-bridged (dca = dicyanamide) linear polynuclear structure. Variable temperature magnetic susceptibility studies indicate weak antiferromagnetic interactions with J values ?0.50 cm?1 and ?0.10 cm?1 for 1 and 2, respectively. 相似文献
76.
The main aim of this research was to study the dynamics of K release from waste mica inoculated with potassium solubilizing microorganism (Bacillus mucilaginosus) and to investigate its effectiveness as potassic-fertilizer using sudan grass (Sorghum vulgare Pers.) var Sudanensis as test crop grown under two Alfisols. Results revealed that application of mica significantly enhanced biomass yield, uptake and per cent K recoveries by sudan grass than control (no-K). Biomass yield, uptake and per cent K recoveries increased further when mica was inoculated with bacterial strain in both the soils than uninoculated mica. Alfisol from Hazaribag recorded higher yield, uptake and K recoveries than Alfisol from Bhubaneswar. The dynamics of K in soils indicated that K was released from mica to water-soluble and exchangeable pools of K due to inoculation of mica with Bacillus mucilaginosus in both the soils. Significantly greater amounts of water-soluble, exchangeable and non-exchangeable K were maintained in Alfisol from Hazaribag than Bhubaneswar. Release kinetics of K showed significant release of K from mica treated with bacterial strain. Significant correlation between biomass yield, K uptake by sudan grass and different pools of K in soils were observed. X-ray diffraction analysis indicates greater dissolution of mica due to inoculation of Bacillus mucilaginosus strain in both the soils. Thus, bio-intervention of waste mica could be an alternative and viable technology to solubilize insoluble K into plant available pool and used efficiently as a source of K-fertilizer for sustaining crop production and maintaining soil potassium. 相似文献
77.
78.
Basab Roy Arindam Chakraborty Sudip K. Ghosh Amit Basak 《Bioorganic & medicinal chemistry letters》2009,19(24):7007-7010
A new class of chimeric molecules have been developed. These are based on polyphenols like catechin and epicatechin and monocyclic β-lactams. The two units are joined via a triazole linker using the ‘Click Chemistry’ conditions. The compounds showed good to weak antibacterial activity against Escherichia coli as well as moderate inhibition of RNase A. 相似文献
79.
A new class of bisenediyne bis sulfones has been synthesized. These molecules underwent cycloaromatization under basic conditions via isomerization to allene and were able to cleave ds-stranded plasmid DNA. 相似文献
80.
Sudeshna Chowdhury Shakuntala Ghorai Samudra Prosad Banik Swagata Pal Soumen Basak Suman Khowala 《Process Biochemistry》2009,44(10):1075-1082
An extracellular sucrase from the culture filtrate of filamentous basidiomycota Termitomyces clypeatus grown on high sucrose (5%, w/v) was purified by gel filtration chromatography, ion exchange chromatography and HPGPLC. The biochemical properties, molecular weight and conformation of sucrase produced were significantly different from the sucrase earlier purified from sucrose (1%, w/v) medium in the fungus. Purified sucrase was characterized as a low molecular weight protein of 13.5 kDa as approximated by SDS-PAGE and HPGPLC and exhibited predominantly random coil conformation in far-UV CD spectra. The enzyme was optimally active at 47 °C and pH 5.0. Km and catalytic activity of the enzyme for sucrose were found to be 3.5 mM and 1.06 U/mg/mM, respectively. The enzyme was maximally active towards sucrose than to raffinose and sucrase activity was significantly inhibited by bivalent metal ions and reducing group agents. The results indicated that due to changes in aggregation pattern, molecular organization of purified sucrase, produced in high sucrose medium, was altered and was different from the previously reported enzyme. This is the first report of a sucrase of such low size showing activity. 相似文献