Browsing by Author "Essiz, Sebnem"

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Citation Count: 0
Investigation of Structural and Antibacterial Properties of WS₂-Doped ZnO Nanoparticles
(Amer Chemical Soc, 2024) Eşsiz, Şebnem; Essiz, Sebnem; Uysal, Bengu Ozugur
ZnO nanoparticles, well-known for their structural, optical, and antibacterial properties, are widely applied in diverse fields. The doping of different materials to ZnO, such as metals or metal oxides, is known to ameliorate its properties. Here, nanofilms composed of ZnO doped with WS2 at 5, 15, and 25% ratios are synthesized, and their properties are investigated. Supported by molecular docking analyses, the enhancement of the bactericidal properties after the addition of WS2 at different ratios is highlighted and supported by the inhibitory interaction of residues playing a crucial role in the bacterial survival through the targeting of proteins of interest.
Citation Count: 0
Modelling of C-terminal tail of human STING and its interaction with tank-binding kinase 1
(Tubitak Scientific & Technical Research Council Turkey, 2022) Eşsiz, Şebnem; Audu-Bida, Hajara; Essiz, Sebnem
Stimulator of interferon genes (STING) plays a significant role in a cell's intracellular defense against pathogens or self DNA by inducing inflammation or apoptosis through a pathway known as cGAS-cGAMP-STING. STING uses one of its domains, the C-terminal tail (CTT) to recruit the members of the pathway. However, the structure of this domain has not been solved experimentally. STING conformation is open and more flexible when inactive. When STING gets activated by cGAMP, its conformation changes to a closed state covered by 4 beta-sheets over the binding site. This conformational change leads to its binding to Tank-binding kinase 1 (TBK1). TBK1 then phosphorylates STING aiding its entry to the cell's nucleus. In this study, we focused on the loop modeling of the CTT domain in both the active and inactive STING conformations. After the modeling step, the active and inactive STING structures were docked to one of the cGAS-cGAMP-STING pathway members, TBK1, to observe the differences of binding modes. CTT loop stayed higher in the active structure, while all the best-scored models, active or inactive, ended up around the same position with respect to TBK1. However, when the STING poses are compared with the cryo-EM image of the complex structure, the models in the active structure chain B displayed closer results to the complex structure.
Citation Count: 0
Newly synthesized 6-substituted piperazine/phenyl-9-cyclopentyl containing purine nucleobase analogs act as potent anticancer agents and induce apoptosis via inhibiting Src in hepatocellular carcinoma cells
(Royal Soc Chemistry, 2023) Eşsiz, Şebnem; Servili, Burak; Altiparmak, Duygu; Servili, Burak; Essiz, Sebnem; Cetin-Atalay, Rengul; Tuncbilek, Meral
Newly synthesized 6-substituted piperazine/phenyl-9-cyclopentyl-containing purine nucleobase analogs were tested for their in vitro anticancer activity against human cancer cells. Compounds 15, 17-24, 49, and 56 with IC50 values less than 10 mu M were selected for further examination on an enlarged panel of liver cancer cell lines. Experiments revealed that compound 19 utilizes its high cytotoxic potential (IC50 < 5 mu M) to induce apoptosis in vitro. Compound 19 displayed a KINOMEscan selectivity score S35 of 0.02 and S10 of 0.01 and demonstrated a significant selectivity against anaplastic lymphoma kinase (ALK) and Bruton's tyrosine kinase (BTK) over other kinases. Compounds 19, 21, 22, 23, and 56 complexed with ALK, BTK, and (discoidin domain-containing receptor 2) DDR2 were analyzed structurally for binding site interactions and binding affinities via molecular docking and molecular dynamics simulations. Compounds 19 and 56 displayed similar interactions with the activation loop of the kinases, while only compound 19 reached toward the multiple subsites of the active site. Cell cycle and signaling pathway analyses exhibited that compound 19 decreases phosho-Src, phospho-Rb, cyclin E, and cdk2 levels in liver cancer cells, eventually inducing apoptosis.
Citation Count: 12
Sustainable production of formic acid from CO2 by a novel immobilized mutant formate dehydrogenase
(Elsevier, 2023) Eşsiz, Şebnem; Servili, Burak; Servili, Burak; Essiz, Sebnem; Binay, Baris; Yildirim, Deniz
Formate dehydrogenase (NAD+-dependent FDH) is an enzyme that catalyzes the reversible oxidation of formate to CO2 while reducing NAD+ to NADH. The enzyme has been used in industrial and chemical applications for NADH regeneration for a long time. However, discovering the unique ability of FDHs, which is to reduce CO2 and produce formic acid, leads studies focusing on discovering or redesigning FDHs. Despite using various protein engineering techniques, these studies mostly target the same catalytic site amino acids of FDHs. Here, for the first time, the effect of an Asp188 mutation on a potential allosteric site in NAD+-dependent CtFDH around its subunit-subunit interface was studied by molecular modelling and simulation in the presence of bicarbonate and formate. Biochemical and kinetic characterization of this Asp188Arg mutant and wild type CtFDH enzymes were performed in detail. Both enzymes were also immobilized on newly synthesized MWCNT-Ni-O-Si/Ald and MWCNT-Ni-O-Si/Glu supports designed to overcome well-known CtFDH stability problems including thermostability and reuse resistance. Integrating mutation and immobilization provided about a 25-fold increase in catalytic efficiency for carbonate activity. The one-way ANOVA analysis also ensured significant effect of the mutation and immobilization on kinetic constants. After characterizing the immobilization of highly purified wild type and mutant enzyme with instrumental analysis techniques, the thermal stability of MWCNT-Ni-Si@wtCtFDH and MWCNT-Ni-Si@mt-CtFDH was found to increase about 11-and 18-fold, respectively, compared to their free counterparts at 50 degrees C. The mutant CtFDH and its immobilized counterpart produced around 2-fold more formic acid than those of wild type CtFDH and its immobilized counterpart under the same conditions. MWCNT-Ni-Si@wt-CtFDH and MWCNT-Ni-Si@mt-CtFDH remained around 82 % and 86 % of their initial activities respectively after lots of recycling. Integration of subunit interface amino acid position of NAD+ dependent FDHs engineering and immobilization provides a new insight can be scientifically and rationally employed for this current application FDHs as a solution to produce formic acids from renewable sources.
Citation Count: 0
Synthesis of New Imidazo[1,2-a]pyridine Triazole Hybrid Molecules as Potential Apoptotic Antitumor Agents
(Wiley-v C H verlag Gmbh, 2024) Eşsiz, Şebnem; Servili, Burak; Servili, Burak; Altundas, Ramazan; Sucu, Bilgesu Onur; Kulu, Irem
Novel imidazo[1,2-a]pyridines bearing 1,2,3-triazole moieties at the C3 position were synthesized. After the characterization of the synthesized compounds, their in vitro therapeutic activities were evaluated in various cancer cell lines (MCF7, A549, HePG2 and T98G). Methoxy substituted derivative was identified as the most potent compound based on the results of its anti-proliferative activity on various cancer cell lines, as well as showing no cytotoxicity on the healthy human fibroblast cell line (MRC-5). As an indicator of apoptosis, a significant decrease in the level of PARP protein was observed in the MCF7 cells treated with this derivative. Molecular docking studies were conducted on wide range of targets such as phosphoinositide 3-kinase (PI3K), cyclin-independent kinase 2 (CDK2), mitogen-activated protein kinase (MEK), insulin-like growth-factor-1 (IGF-1), tubulin, DNA topoisomerase, poly (ADP-ribose) polymerase (PARP) and B-cell lymphoma-2 (BCL2). All the compounds tested showed the lowest binding energies with target PARP1. Moreover, CDK2 and tubulin displayed relatively good binding scores. The docking poses and scores were cross-checked with two different software and multiple protein conformations were included to incorporate flexible protein docking features. Finally, drug-likeness properties of the compounds are further tested via Swiss-ADME software. Novel imidazo[1,2-a]pyridine-1,2,3-triazole derivatives have been synthesized and evaluated for antiproliferative activity against MCF7, A549, HePG2, T98G cell lines. Compound 5c was found to be more potent on PARP protein in MCF7 cell line. The synthesized compounds were docked to PI3K, CDK2, MEK1, IGF-1, TUB1, DNA topoisomerase, PARP1, and BCL2. The best docking poses for PARP1 and CDK2 were obtained from 5c, 5d and 5 f. image