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Int J Biol Macromol,
2016]
Brugia malayi Glucose 6-phosphate dehydrogenase apoenzyme (BmG6PD) was expressed and purified by affinity chromatography to study the differences in kinetic properties of enzyme and the effect of the cofactor NADP(+) binding on enzyme stability. The presence of cofactor NADP(+) influenced the tertiary structure of enzyme due to significant differences in the tryptophan microenvironment. However, NADP(+) binding have no effect on secondary structure of the enzyme. Quenching with acrylamide indicated that two or more tryptophan residues became accessible upon cofactor binding. Unfolding and cross linking study of BmG6PD showed that NADP(+) stabilized the protein in presence of high concentration of urea/GdmCl. A homology model of BmG6PD constructed using human G6PD (PDB id: 2BH9) as a template indicated 34% -helix, 19% -sheet and 47% random coil conformations in the predicted model of the enzyme. In the predicted model binding of NADP(+) to BmG6PD was less tight with the structural sites (-10.96 KJ/Mol binding score) as compared with the coenzyme site (-15.47 KJ/Mol binding score).
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J Biol Chem,
2004]
The consequences of mitochondrial dysfunction are not limited to the development of oxidative stress or initiation of apoptosis but can result in the establishment of stress tolerance. Using maize mitochondrial mutants, we show that permanent mitochondrial deficiencies trigger novel Ca2+-independent signaling pathways, leading to constitutive expression of genes for molecular chaperones, heat shock proteins (HSPs) of different classes. The signaling to activate hsp genes appears to originate from a reduced mitochondrial transmembrane potential. Upon depolarization of mitochondrial membranes in transient assays, gene induction for mitochondrial HSPs occurred more rapidly than that for cytosolic HSPs. We also demonstrate that in the nematode Caenorhabditis elegans transcription of hsp genes can be induced by RNA interference of nuclear respiratory genes. In both organisms, activation of hsp genes in response to mitochondrial impairment is distinct from their responses to heat shock and is not associated with oxidative stress. Thus, mitochondria-to-nucleus signaling to express a hsp gene network is apparently a widespread retrograde mechanism to facilitate cell defense
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J Enzyme Inhib Med Chem,
2013]
The aspartic protease inhibitory efficiency of rBm-33, an aspin from a filarial parasite Brugia malayi was investigated. rBm-33 was found to be thermostable up to 90C and it forms a stable 'enzyme-product' complex with human pepsin. Aspartic protease inhibitory activity was investigated using UV spectroscopy and isothermal titration calorimetry. Our results suggest that rBm-33 inhibits the activity of important human aspartic proteases that were examined with binding constants (Kb) values between 10.23 x 10(3) and 6.52 x 10(3) M(-1). The binding reactions were enthalpy driven with Hb values between -50.99 and -46.07 kJ mol(-1). From kinetic studies, pepsin inhibition by rBm-33 was found to be linear competitive with an inhibition constant (Ki) of 2.5 (+/-0.8) nM. Because of the inhibitory efficacy of Bm-33 against important human aspartic proteases which play a vital role in immune-regulation along with other functions, Bm-33 can be projected as a drug target for the filariasis.
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Genomics,
2018]
Identification of exon location in a DNA sequence has been considered as the most demanding and challenging research topic in the field of Bioinformatics. This work proposes a robust approach combining the Trigonometric mapping with Adaptive tuned Kaiser Windowing approach for locating the protein coding regions (EXONS) in a genetic sequence. For better convergence as well as improved accurateness, the side lobe height control parameter () of Kaiser Window in the proposed algorithm is made adaptive to track the changing dynamics of the genetic sequence. This yields better tracking potential of the anticipated Adaptive Kaiser algorithm as it uses the recursive Gauss Newton tuning which in turn utilizes the covariance of the error signal to tune the factor which has been shown through numerous simulation results under a variety of practical test conditions. A detailed comparative analysis with the existing mapping schemes, windowing techniques, and other signal processing methods like SVD, AN, DFT, STDFT, WT, and ST has also been included in the paper to focus on the strength and efficiency of the proposed approach. Moreover, some critical performance parameters have been computed using the proposed approach to investigate the effectiveness and robustness of the algorithm. In addition to this, the proposed approach has also been successfully applied on a number of benchmark gene sets like Musmusculus, Homosapiens, and C. elegans, etc., where the proposed approach revealed efficient prediction of exon location in contrast to the other existing mapping methods.