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231.
Syeda Rehana Zia 《Molecular simulation》2018,44(17):1411-1425
Interleukin-2 (IL-2) protein belongs to the signal modulator cytokine's family and therefore it is prevalent for immunological responses. It has been identified as a centrally important potential drug target for the inhibition of protein-protein interactions; so as to suppress the immunological responses associated with autoimmune, inflammatory and immunological diseases, and cancer. In the present work, we have performed two independent 100?ns of molecular dynamics (MD) simulations on the apo IL-2 protein and its ligand-bound complex (with a potent inhibitor FRG), to study the effect of inhibitor binding on the dynamics and stability of the protein. The calculation of binding free energy via post-processing end state method of Molecular Mechanics Poisson Boltzmann Surface Area (MM-PBSA) and Molecular Mechanics Generalised Born Surface Area (MM-GBSA) has inferred a good correlation in accordance with the already reported experimental data, demonstrating that the free energy of binding calculated by the two methods has no significant difference. The investigation of individual components of free energy revealed that the association of IL-2 protein with FRG ligand is primarily driven by the van der Waals energy contribution that represents the non-polar/hydrophobic energy contribution as dominant in this case of ligand binding. 相似文献
232.
Tooba Siddiqui Mohammad Khalid Zia Haseeb Ahsan 《Journal of biomolecular structure & dynamics》2020,38(14):4107-4118
Abstract Quercetin is a widely used bioflavonoid found in onions, grapes, berries and citrus fruits. Under certain conditions, quercetin acts as a pro-oxidant thereby generating reactive oxygen species and promoting the oxidation of molecules. Our study investigates the effect of quercetin on the structure and function of alpha-2-macroglobulin (α2M) by employing various biophysical techniques and trypsin inhibitory assay. α2M is the major antiproteinase present in the plasma of vertebrates. Results of activity assay indicated that α2M loses its 56% of inhibitory activity on treatment with quercetin in the presence of light. UV spectroscopy reveals hyper chromaticity in absorption spectra of protein on interaction with quercetin suggesting structural change. The intrinsic fluorescence studies showed quenching of α2M spectra in the presence of quercetin, and the mode of quenching was found to be static in nature. Synchronous fluorescence indicated the alteration in the microenvironment of tryptophan residues. CD and FTIR spectroscopy confirms concentration-dependent alterations in secondary structure of α2M instigated by quercetin. The magnitude of binding constant, enthalpy change, entropy change and free energy change during the interaction process was determined by isothermal titration calorimetry. Hydrogen bonding and hydrophobic interaction were the main intermolecular forces involved during the process. This study identifies and signifies the damage induced by quercetin to α2M due to its pro-oxidant action. Communicated by Ramaswamy H. Sarma 相似文献
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Misbah SultanKhalid Mahmood Zia Haq Nawaz BhattiTahir Jamil Rizwan HussainMohammad Zuber 《Carbohydrate polymers》2012,87(1):397-404
Polyurethane (PU) prepolymers were prepared by using two different diisocyanates i.e., toluene-2,4-diisocyanate (TDI) and or isophorone diisocyanate (IPDI), and poly (2-methyl-1,3-propylene glutarate), hydroxyl terminated group. PU prepolymer was reacted with 2-hydroxyethylacrylate (HEA) to form vinyl terminated PU prepolymer. Vinyl terminated PU prepolymers were further copolymerized with butyl acrylates (BuA) by emulsion process. The structure of proposed PUACs samples was confirmed by FT-IR, and their physicochemical properties were studied determining solid contents (%), emulsion stability and its appearance, tackiness and film appearance. Their acids and base chemical resistance was also studied and discussed. The synthesized PUACs samples were applied using dip-padding techniques on mill un-desized poly-cotton plain weave fabrics. The results emphasis that PUACs based on toluene-2,4-diisocyanate (TDI) have shown excellent performance against physical and chemical resistance as compared to isophorone diisocyanate (IPDI) based PUACs, however vice versa results were found in some studies. 相似文献
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Jií Dostl Jií Brynda Lucie Vakov Syeda Rehana Zia Iva Pichov Olga Heidingsfeld Martin Lepík 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):914
Pathogenic Candida albicans yeasts frequently cause infections in hospitals. Antifungal drugs lose effectiveness due to other Candida species and resistance. New medications are thus required. Secreted aspartic protease of C. parapsilosis (Sapp1p) is a promising target. We have thus solved the crystal structures of Sapp1p complexed to four peptidomimetic inhibitors. Three potent inhibitors (Ki: 0.1, 0.4, 6.6 nM) resembled pepstatin A (Ki: 0.3 nM), a general aspartic protease inhibitor, in terms of their interactions with Sapp1p. However, the weaker inhibitor (Ki: 14.6 nM) formed fewer nonpolar contacts with Sapp1p, similarly to the smaller HIV protease inhibitor ritonavir (Ki: 1.9 µM), which, moreover, formed fewer H-bonds. The analyses have revealed the structural determinants of the subnanomolar inhibition of C. parapsilosis aspartic protease. Because of the high similarity between Saps from different Candida species, these results can further be used for the design of potent and specific Sap inhibitor-based antimycotic drugs. 相似文献
238.
Lauric acid alleviates insulin resistance by improving mitochondrial biogenesis in THP-1 macrophages
Tham Yong Yao Choo Quok Cheong Muhammad Tengku Sifzizul Tengku Chew Choy Hoong 《Molecular biology reports》2020,47(12):9595-9607
Molecular Biology Reports - Mitochondrial dysfunction plays a crucial role in the central pathogenesis of insulin resistance and type 2 diabetes mellitus. Macrophages play important roles in the... 相似文献
239.
Mycopathologia - Cigarette smoke is associated with higher oral Candida carriage and possible predisposition and increased susceptibility to oral candidal infection. Candida dubliniensis is... 相似文献
240.
Tesfaye Worku Kai Wang Duncan Ayers Di Wu Zia Ur Rehman Hao Zhou 《Cell cycle (Georgetown, Tex.)》2018,17(7):892-902
Recent findings suggest that ephrinA5 (Efna5) has a novel role in female mouse fertility, in addition to its well-defined role as a neurogenesis factor. Nevertheless, its physiological roles in ovarian granulosa cells (GC) have not been determined. In this study, mouse GC were cultured and transfected with ephrin A5 siRNA and negative control to determine the effects of Efna5 on GC apoptosis, proliferation, cell cycle progression, and related signaling pathways. To understand the mode signaling, the mRNA expression levels of Efna5 receptors (Eph receptor A5, Eph receptor A3, Eph receptor A8, and Eph receptor B2) were examined. Both mRNA and protein expressions of apoptosis-related factors (Bax, Bcl-2, Caspase 8, Caspase 3, and Tnfα) and a proliferation marker, Pcna, were investigated. Additionally, the role of Efna5 on paracrine oocyte-secreted factors and steroidogenesis hormones were also explored. Efna5 silencing suppressed GC apoptosis by downregulating Bax and upregulating Bcl-2 in a Caspase 8-dependent manner. Efna5 knockdown promoted GC proliferation via p-Akt and p-ERK pathway activation. The inhibition of Efna5 enhanced BMH15 and estradiol expression, but suppressed GDF9, while progesterone level remained unaltered. These results demonstrated that Efna5 is a pro-apoptotic agent in GC and plays important role in folliculogenesis by mediating apoptosis, proliferation, and steroidogenesis in female mouse. Therefore Efna5 might be potential therapeutic target for female fertility disorders. 相似文献