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111.
Tijjani Salihu Shinkafi Abhinav Kaushik Amena Mahmood Ambrish Kumar Tiwari Mohammad Mumtaz Alam Mymoona Akhter 《Journal of biomolecular structure & dynamics》2020,38(10):2976-2987
AbstractThis study identifies and validates hexokinase type 4 (HK4), an isozyme of hexokinase in the liver and pancreas, as an important target of C2-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (βdGT), a xanthone glucoside suggested to have antidiabetic property. In the study, we applied the computational pipeline of molecular docking followed by the molecular dynamics simulations to shortlist potential βdGT protein targets. The analysis of protein dynamics and the binding free energy (ΔG) led us to the identification of HK4 as a key βdGT target, whereby the binding mode and domain dynamics suggested the activator function of βdGT. βdGT bound to the allosteric site of the isozyme ~13?Å away from the substrate (glucose)-binding site. The binding free energy of the ligand-protein complex was energetically feasible (ΔG, –41.61?kcal/mol) and the cleft angle deviation between the two (small and large) domains of HK4 revealed differential HK4 dynamics in response to βdGT binding. 3D structure analysis of the isozyme-ligand complex highlighted the role of Arg63, Glu67 and Lys458 in ligand stabilization and hydrophobic interactions mediated by Tyr214 and Met235. Experimental validation of the results of computational analysis confirmed the activator function of βdGT on HK4. The study has implication in diabetes as βdGT may be used to lower the blood glucose level by activating hepatic and pancreatic hexokinase without the risk of hypoglycemia.Communicated by Ramaswamy H. Sarma 相似文献
112.
Md. Saimul Islam Hemantika Dasgupta Mukta Basu Anup Roy Neyaz Alam Susanta Roychoudhury Chinmay Kumar Panda 《Journal of cellular physiology》2020,235(11):8114-8128
Triple negative breast cancer (TNBC) originates from a less differentiated ductal cell of breast, which is less sensitive to chemotherapy. The chemotolerance mechanism of TNBC has not yet been studied in detail. For this reason, molecular profiles (expression/genetic/epigenetic) of Y654-p-β-catenin (active) and its kinase epidermal growth factor receptor (EGFR) along with SH3GL2 (regulator of EGFR homeostasis) were compared between neoadjuvant chemotherapy treated (NACT) and pretherapeutic TNBC samples. Reduced nuclear expression of Y654-p-β-catenin protein with low proliferation index and CD44 prevalence showed concordance with reduced expression of EGFR/Y1045-p-EGFR proteins in the NACT samples than the pretherapeutic TNBC samples. Infrequent messenger RNA expression, gene amplification (10–32.5%), and mutation (1%) of EGFR were seen in the TNBC samples irrespective of therapy, suggesting the importance of EGFR protein stabilization in this tumor. The upregulation of SH3GL2 seen in the NACT samples in contrast to the pretherapeutic samples might be due to its promoter hypomethylation, as seen in the quantitative methylation assay. A similar trend of upregulation of SH3GL2 and downregulation of EGFR, Y1045-p-EGFR, Y654-p-β-catenin were seen in the MDA-MB-231 cell line using antharacycline antitumor drugs (doxorubicin/nogalamycin). The NACT patients with reduced expression of Y654-p-β-catenin and/or EGFR and high expression of SH3GL2 showed comparatively better prognosis than the pretherapeutic patients. Thus, our study showed that reduced nuclear expression of Y654-p-β-catenin in NACT samples due to downregulation of EGFR protein through promoter hypomethylation-mediated upregulation of SH3GL2, resulting in low proliferation index/CD44 prevalence with better prognosis of the NACT patients, might have an important role in the chemotolerance of TNBC. 相似文献
113.
Zaki A. Siddiqui Mohd. Shehzad Subha Alam 《Archives Of Phytopathology And Plant Protection》2013,46(4):449-455
Effect of interactions of Meloidogyne incognita with Ralstonia solanacearum and interaction of M. incognita with Pectobacterium carotovorum were studied in sequential and simultaneous inoculations on potato (Solanum tuberosum). Inoculation of M. incognita caused a lesser reduction in plant growth than caused by R. solanacearum. Inoculation of M. incognita plus R. solanacearum caused a greater reduction in plant growth than the damage caused by either pathogen. Inoculation of M. incognita prior to R. solanacearum resulted in a greater reduction in plant growth than R. solanacearum was inoculated prior to M. incognita. However, inoculation of M. incognita or P. carotovorum caused similar reduction in plant growth. Inoculation of P. carotovorum prior to M. incognita caused lesser reduction in plant growth than simultaneous inoculation of both pathogens. Inoculation of M. incognita caused galling in potato roots but the size of galls was small. Inoculation of P. carotovorum or R. solanacearum with M. incognita had adverse effect on galling and nematode multiplication. Wilting or soft rot index was 3 when R. solanacearum or P. carotovorum was inoculated alone. In other treatments, where R. solanacearum or P. carotovorum was inoculated with M. incognita, wilting or soft rot indices were 5. 相似文献
114.
S. T. Chandel H. S. Gaur M. M. Alam 《Archives Of Phytopathology And Plant Protection》2013,46(3):195-200
The effects of puddling and water regimes on hydraulic conductivity (cm/day) of soil and on bulk density (mg/m 3 ) during rice culture, soil physical characteristics of the experimental field population densities of plant-parasitic nematodes have been studied. Puddling reduced the bulk density of soil and decreased the hydraulic conductivity in the upper layers but not in the deeper layers of soil aeration was reduced due to high moisture levels retained in the puddled soil. Population density of M. triticoryzae declined in puddled soil. The invasion of the roots by the second-generation infective juveniles was reduced. The population density of the root-knot nematodes was higher in the non-puddled soil especially in unsubmerged condition compared to puddled and submerged soil. However, if the seedlings were already infected before transplanting and submergence, the nematode could survive well and reproduce within the aerenchyma of the root. 相似文献
115.
S. T. Chandel H. S. Gaur M. M. Alam 《Archives Of Phytopathology And Plant Protection》2013,46(4):287-290
Abstract Horsfall, J. G. (Ed.): Annual Review of Phytopathology. Vol. 4. VII + 423 S. Palo Alto, 1966: Annual Reviews, Inc. Leinen, 9,00 $. Reviewed by K. Naumann. Gregory, P. H. und Monteith, J. L. (Ed.): Airborne microbes. Seventeenth Symposium of the Society for General Microbiology held at the Imperial College, London April 1967. XII + 385 S., mit Abb. u. Tab. London, 1967: Cambridge University Press, Leinenrücken, 75 s. Reviewed by H. J. Müller. Raper, J. R.: Genetics of sexuality in higher fungi. VIII + 283 S., mit Abb. u. Tab., New York, 1966: The Ronald Press Company, Leinen, 12,00 $. Reviewed by M. Schmiedeknecht. Albrecht, F. O.: Polymorphisme phasaire et biologie des acridiens migrateurs. X + 194 S., 52 Abb. Paris, 1967: Masson et Cie, Éditeurs, karton., 50 F. Reviewed by R. Fritzsche. Wigglesworth, V. B.: Insect physiology. VII + 134 S., 12 Abb., London, 1966: Methuen &; Co Ltd., brosch., 10 s 6 d. Reviewed by G. Schäller. Machlis, L. (Ed.): Annual Review of Plant Physiology. Vol. 18. VIII + 480 S., mit Abb. u. Tab., Palo Alto, Ca., 1967: Annual Reviews, Inc., Leinen, 9,00 $. Reviewed by H. Wolffgang. Newton, B. A. und Reynolds, P. E. (Ed.): Biochemical studie of antimicrobial drugs. (Sixteenth symposium of the Society for General Microbiology held at the Royal Institution, London, April 1966). X + 349 S., mit Abb. u. Tab., London, 1966: Cambridge University Press, Halbleinen, 60 s. Reviewed by H. J. Müller. Pilet, P.-É.: La cellule, structure et fonctions. 406 S., 310 Abb.; 32 ganzs. Abb., Paris 1966: Schwarz-Weiß-Tafeln. Masson et Cie, Editeurs, brosch. 38 F. Reviewed by K. Schmelzer. Ciba (Ed.): Dimecron 257 S. Basle, Switzerland, 1967: P.O. Box — CIBA — Kunststoff Reviewed by Horst Beitz. Bellamy, L. J.: Ultrarot-Spektrum und chemische Konstitution. 2. Auflage, 325 S., 11 Abb., 23 Tab. Darmstadt, 1966: Dr. Dietrich Steinkopff Verlag, kart., 28,— DM Reviewed by Volker Müller. Bahr, G. F.; Zeitler, E. H. (Ed.): Quantitative electron microscopy. 1965, VIII + 605 (1340) S., mit Abb. u. Tab., Leinen, 16,00 $, Baltimore (Md.), The Williams &; Wilkins Company. Reviewed by H. B. Schmidt. 相似文献
116.
S. Datta R. G. Choudhary Md. Shamim Vishwa Dhar 《Archives Of Phytopathology And Plant Protection》2013,46(6):558-566
Fusarium species causing wilt diseases in different plants were characterised by comparing nonpathogenic and different pathogenic species using rDNA RFLP analysis. The ITS (internal transcribed spacer) region of 12 isolates belonging to the section Elegans, Laseola, Mortiella, Discolor, Gibbosum, Lateritium and Sporotrichiella were amplified by universal ITS primers (ITS-1 and ITS-4) using polymerase chain reaction (PCR). Amplified products, which ranged from 522 to 565 bp were obtained from all 12 Fusarium isolates. The amplified products were digested with seven restriction enzymes, and restriction fragment length polymorphism (RFLP) patterns were analysed. A dendrogram derived from PCR-RFLP analysis of the rDNA region divided the Fusarium isolates into three major groups. Assessment of molecular variability based on rDNA RFLP clearly indicated that Fusarium species are heterogeneous and most of the forma speciales have close evolutionary relationships. 相似文献
117.
Lucy Wentworth Justin V. Meyers Sheeba Alam Andrew J. Russ M. Suresh Clifford S. Cho 《Cancer immunology, immunotherapy : CII》2013,62(1):149-159
We have previously observed that in vivo exposure to growing melanoma tumors fundamentally alters activated T cell homeostasis by suppressing the ability of naïve T cells to undergo antigen-driven proliferative expansion. We hypothesized that exposure of T cells in later stages of differentiation to melanoma would have similar suppressive consequences. C57BL/6 mice were inoculated with media or syngeneic B16F10 melanoma tumors 8 or 60 days after infection with lymphocytic choriomeningitis virus (LCMV), and splenic populations of LCMV-specific T cells were quantified using flow cytometry 18 days after tumor inoculation. Inoculation with melanoma on post-infection day 8 potentiated the contraction of previously activated T cells. This enhanced contraction was associated with increased apoptotic susceptibility among T cells from tumor-bearing mice. In contrast, inoculation with melanoma on post-infection day 60 did not affect the ability of previously established memory T cells to maintain themselves in stable numbers. In addition, the ability of previously established memory T cells to respond to LCMV challenge was unaffected by melanoma. Following adoptive transfer into melanoma-bearing mice, tumor-specific memory T cells were significantly more effective at controlling melanoma growth than equivalent numbers of tumor-specific effector T cells. These observations suggest that memory T cells are uniquely resistant to suppressive influences exerted by melanoma on activated T cell homeostasis; these findings may have implications for T cell–based cancer immunotherapy. 相似文献
118.
Faizul Azam Honiwa Suliman Abodabos Ismail M. Taban Abdalla R. Rfieda Danish Mahmood Md Jamir Anwar 《Molecular simulation》2013,39(18):1563-1571
ABSTRACTInhibitors of monoamine oxidase (MAO)-B have been used for many years in the therapy of Parkinson’s disease (PD). Owing to the safety concerns of the currently used agents, the discovery of novel scaffolds is of considerable interest. MAO-B inhibitory potential of rutin, a flavonoid derived from natural sources, has been established in experimental findings. Hence, the current study seeks to examine the interactions between rutin and crystal structure of human MAO-B enzyme. Molecular docking calculations, as well as molecular dynamics simulations, were employed to investigate the binding mode and the stability of the rutin/MAO-B complex. Energies of highest occupied/lowest unoccupied molecular orbitals were computed through DFT studies and used to calculate electron affinity, hardness, chemical potential, electronegativity, and electrophilicity index in order to investigate the capability of these parameters to influence the ligand–receptor interactions. It was found that rutin traverses both the entrance cavity and the substrate cavity, forcing the Ile-199 ‘gate’ to rotate into its open conformation. It results in the fusion of the two cavities of the MAO-B binding site and directly leads to better binding interactions. Results of the current study can be used for lead modification and development of novel drugs for the treatment of PD. 相似文献
119.
Abdullah Naiyer Md. Imtaiyaz Hassan Asimul Islam Monica Sundd 《Journal of biomolecular structure & dynamics》2013,31(10):2267-2284
Almost all proteins fold via a number of partially structured intermediates such as molten globule (MG) and pre-molten globule states. Understanding the structure of these intermediates at atomic level is often a challenge, as these states are observed under extreme conditions of pH, temperature, and chemical denaturants. Furthermore, several other processes such as chemical modification, site-directed mutagenesis (or point mutation), and cleavage of covalent bond of natural proteins often lead to MG like partially unfolded conformation. However, the dynamic nature of proteins in these states makes them unsuitable for most structure determination at atomic level. Intermediate states studied so far have been characterized mostly by circular dichroism, fluorescence, viscosity, dynamic light scattering measurements, dye binding, infrared techniques, molecular dynamics simulations, etc. There is a limited amount of structural data available on these intermediate states by nuclear magnetic resonance (NMR) and hence there is a need to characterize these states at the molecular level. In this review, we present characterization of equilibrium intermediates by biophysical techniques with special reference to NMR. 相似文献
120.