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31.
Mehdi Adib Fariba Peytam Reihaneh Shourgeshty Maryam Mohammadi-Khanaposhtani Mehdi Jahani Somaye Imanparast Mohammad Ali Faramarzi Bagher Larijani Ali Akbar Moghadamnia Ensieh Nasli Esfahani Fatemeh Bandarian Mohammad Mahdavi 《Bioorganic & medicinal chemistry letters》2019,29(5):713-718
Twenty three fused carbazole–imidazoles 6a–w were designed, synthesized, and screened as new α-glucosidase inhibitors. All the synthesized fused carbazole-imidazoles 6a-w were found to be more active than acarbose (IC50?=?750.0?±?1.5?µM) against yeast α-glucosidase with IC50 values in the range of 74.0?±?0.7–298.3?±?0.9?µM. Kinetic study of the most potent compound 6v demonstrated that this compound is a competitive inhibitor for α-glucosidase (Ki value?=?75?µM). Furthermore, the in silico studies of the most potent compounds 6v and 6o confirmed that these compounds interacted with the key residues in the active site of α-glucosidase. 相似文献
32.
Brain Cytochrome Oxidase in Alzheimer''s Disease 总被引:5,自引:0,他引:5
Stephen J. Kish Catherine Bergeron Ali Rajput† Slobodan Dozic‡ Frank Mastrogiacomo Li-Jan Chang Julie M. Wilson Linda M. DiStefano Jose N. Nobrega§ 《Journal of neurochemistry》1992,59(2):776-779
A recent demonstration of markedly reduced (-50%) activity of cytochrome oxidase (CO; complex 4), the terminal enzyme of the mitochondrial enzyme transport chain, in platelets of patients with Alzheimer's disease (AD) suggested the possibility of a systemic and etiologically fundamental CO defect in AD. To determine whether a CO deficiency occurs in AD brain, we measured the activity of CO in homogenates of autopsied brain regions of 19 patients with AD and 30 controls matched with respect to age, postmortem time, sex, and, as indices of agonal status, brain pH and lactic acid concentration. Mean CO activity in AD brain was reduced in frontal (-26%: p less than 0.01), temporal (-17%; p less than 0.05), and parietal (-16%; not significant, p = 0.055) cortices. In occipital cortex and putamen, mean CO levels were normal, whereas in hippocampus, CO activity, on average, was nonsignificantly elevated (20%). The reduction of CO activity, which is tightly coupled to neuronal metabolic activity, could be explained by hypofunction of neurons, neuronal or mitochondrial loss, or possibly by a more primary, but region-specific, defect in the enzyme itself. The absence of a CO activity reduction in all of the examined brain areas does not support the notion of a generalized brain CO abnormality. Although the functional significance of a 16-26% cerebral cortical CO deficit in human brain is not known, a deficiency of this key energy-metabolizing enzyme could reduce energy stores and thereby contribute to the brain dysfunction and neurodegenerative processes in AD. 相似文献
33.
Stachybotrys microspora is a filamentous fungus that produces various β-glucosidases, of which two have already been characterized. The present study reports on the production of a third one, named bglG, in the presence of d-glucose used as a sole carbon source, and on its subsequent purification and characterization. Although efficiently produced in the presence of d-glucose, bglG continues to be highly inhibited by this sugar. In fact, the addition of d-glucose significantly decreases the glucose formation rates during the hydrolysis of pNPG. This work reports on the effect of various carbohydrates on bglG activity in order to understand the mechanisms adopted by d-glucose to inhibit this enzyme. The findings indicate that bglG is strongly inhibited by d-glucose (44% of the relative activity at 5 mM), d-glucitol (96% of the relative activity), d-mannose (56% of the relative activity), cellobiose and maltose (72% and 71% of the relative activity, respectively). On the other hand, d-galactose, d-fructose, lactose, and sucrose have no effect on bglG activity. Similarly, several isomers, such as 2-acetamido-2-deoxy-d-glucose and 2-deoxy-d-arabino-hexose (2-deoxy-d-glucose) were noted to bring no change on the relative activity of bglG. d-xylose and xylitol, on the other hand, enhanced bglG activity up to 123% and 120% of relative activity, respectively. Accordingly, the configuration, epimerisation, isomerisation, and substitutions played key roles in bglG inhibition. The effect of the combination of iron (the best activator of bglG, 161%) with some of those additives was also investigated. The findings revealed that, while a combination of iron at a concentration of 10 mM with d-glucose resulted in a two-fold decrease in bglG inhibition (84% at 5 mM), iron maintained the same effect with the remainder of the additives being tested. 相似文献
34.
Salehi Jouzani G Seifinejad A Saeedizadeh A Nazarian A Yousefloo M Soheilivand S Mousivand M Jahangiri R Yazdani M Amiri RM Akbari S 《Canadian journal of microbiology》2008,54(10):812-822
The characterization of nematode-effective strains and cry genes in the Iranian Bacillus thuringiensis (Bt) collection (70 isolates) is presented. Characterization was based on PCR analysis using 12 specific primers for cry5, cry6, cry12, cry13, cry14, and cry21 genes encoding proteins active against nematodes, crystal morphology, and protein band patterns as well as their nematicidal activity on root-knot nematode (Meloidogyne incognita) and two free-living nematodes (Chiloplacus tenuis and Acrobeloides enoplus). PCR results with primers for these genes showed that 22 isolates (31.5%) contain a minimum of one nematode-active cry gene. Strains containing the cry6 gene were the most abundant and represent 22.8% of the isolates. Bt strains harboring cry14 genes were also abundant (14.2%). cry21 and cry5 genes were less abundant, found in 4.2% and 2.8% of the strains, respectively. In total, six different nematode-active cry gene profiles were detected in this collection. Four isolates did not show the expected PCR product size for cry5, cry6, and cry21 genes; they might contain potentially novel insecticidal crystal protein genes. Twenty-two Bt isolates containing nematode-active cry genes were selected for preliminary bioassays on M. incognita. Based on these bioassays, four isolates were selected for detailed bioassays. Isolates YD5 and KON4 at 2 x 10(8) CFU/mL concentrations showed 77% and 81% toxicity on M. incognita, respectively. The free-living nematodes C. tenuis and A. enoplus were more susceptible and the highest mortality was observed within 48 h of incubation at all of the concentrations tested. Maximum mortality was recorded for isolates SN1 and KON4 at 2 x 10(8) CFU/mL concentrations and resulted in 68% and 77% adults deaths of C. tenuis and 68% and 72% for A. enoplus, respectively. Our results showed that PCR is a useful technique for toxicity prediction of nematicidal Bt isolates. 相似文献
35.
36.
Muhammad Muzammal Adeel Muhammad Qasim Usman Ali Ashfaq Muhammad Shareef Masoud Mahmood ur Rehman Muhammad Tahir ul Qamar Muhammad Rizwan Javed 《Bioinformation》2014,10(7):454-459
Computational tools occupy the prime position in the analysis of large volume of post-genomic data. These tools have advantage
over the wet lab experiments in terms of high coverage, cost and time. Breast cancer is the most common cancer in females
worldwide. It is a genetically heterogeneous disorder and many genes are involved in the pathway of the disease. Mutations in
metastasis suppressor gene are the major cause of the disease. In this study, the effects of mutations in breast cancer metastasis
suppressor 1gene upon protein structure and function were examined by means of computational tools and information from
databases.This study can be useful to predict the potential effect of every allelic variant, devise new biological experiments and to
interpret and predict the patho-physiological impact of new mutations or non-synonymous polymorphisms. 相似文献
37.
Irum Sidra Andleeb Saadia Ali Amjad Rashid Muhammad Ibrahim Majid Mahnoor 《International journal of peptide research and therapeutics》2021,27(4):2313-2331
International Journal of Peptide Research and Therapeutics - Pseudomonas aeruginosa (P. aeruginosa) is a critical healthcare challenge due to its ability to cause persistent infections and the... 相似文献
38.
Tong L Lin Q Wong WK Ali A Lim D Sung WL Hew CL Yang DS 《Protein expression and purification》2000,18(2):175-181
HPLC6 is the major component of liver-type antifreeze polypeptides (AFPs) from the winter flounder, Pleuronectes americanus. To facilitate mutagenesis studies of this protein, a gene encoding the 37-amino acid mature polypeptide was chemically synthesized and cloned into the Tac cassette immediately after the bacterial ompA leader sequence for direct excretion of the AFP into the culture medium. Escherichia coli transformant with the construct placIQpar8AF was cultured in M9 medium. The recombinant AFP (rAFP) was detected by a competitive enzyme-linked immunosorbent assay (ELISA). After IPTG induction, a biologically active rAFP was expressed. The majority of the rAFP was excreted into the culture medium with only trace amounts trapped in the periplasmic space and cytoplasm. After 18 h of induction, the accumulated rAFP in the culture medium amounted to about 16 mg/L. The excreted AFP was purified from the culture medium by a single-step reverse-phase HPLC. Mass spectrometric and amino acid composition analyses confirmed the identity of the purified product. The rAFP, which lacked amidation at the C-terminal, was about 70% active when compared to the amidated wild-type protein, thus confirming the importance of C-terminal cap structure in protein stability and function. 相似文献
39.
Proteases are one of the highest value commercial enzymes as they have broad applications in food, pharmaceutical, detergent, and
dairy industries and serve as vital tools in determination of structure of proteins and polypeptides. Multiple application of these
enzymes stimulated interest to discover them with novel properties and considerable advancement of basic research into these
enzymes. A broad understanding of the active site of the enzyme and of the mechanism of its inactivation is essential for
delineating its structure-function relationship. Primary structure analysis of alkaline protease showed 42% of its content to be alpha
helix making it stable for three dimensional structure modeling. Homology model of alkaline protease has been constructed using
the X-ray structure (3F7O) as a template and swiss model as the workspace. The model was validated by ProSA, SAVES,
PROCHECK, PROSAII and RMSD. The results showed the final refined model is reliable. It has 53% amino acid sequence identity
with the template, 0.24 Å as RMSD and has -7.53 as Z-score, the Ramachandran plot analysis showed that conformations for 83.4 %
of amino acid residues are within the most favored regions and only 0.4% in the disallowed regions. 相似文献