Şebnem Eşsiz

Eşsiz, Şebnem

Name Variants

Eşsiz, Şebnem
Eşsiz, Sebnem
E., Sebnem
Sebnem Eşsiz
Eşsiz, Ş.
Essiz, Sebnem
Essiz,Sebnem
Şebnem Eşsiz
S. Eşsiz
Essiz,Ş.
E., Şebnem
Eşsiz, S.
DAVUTYAN N.
Eşsiz, ŞEBNEM
Ş. Eşsiz
Şebnem EŞSIZ
Eşsiz,Ş.
EŞSIZ, Şebnem
E.,Sebnem
Essiz,S.
ŞEBNEM EŞSIZ
Sebnem, Essiz
Davutyan N.
EŞSIZ, ŞEBNEM
Gökhan, Şebnem Eşsiz
Eşsiz, Şebnem
Eşsiz Gökhan, Şebnem
Gökhan Eşsiz, Şebnem
Gökhan, Şebnem Eşsiz
Essız, Sebnem
Eşsiz, Şebnem
Essız, Sebnem
Eşsiz Gökhan, Şebnem

Job Title

Dr. Öğr. Üyesi

Email Address

sebnem.gokhan@khas.edu.tr

Main Affiliation

Molecular Biology and Genetics

Sustainable Development Goals Report Points

SDG data could not be loaded because of an error. Please refresh the page or try again later.

Scholarly Output

23

Articles

13

Citation Count

135

Supervised Theses

7 Scholarly Output Search Results

Now showing 1 - 10 of 22

Citation - WoS: 28
Citation - Scopus: 29
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; Core Program; Molecular Biology and Genetics
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 - WoS: 0
Soman as a Wrench in the Works of Human Acetylcholinesterase: Soman Induced Conformational Changes Revealed by Molecular Dynamics Simulations
(Amer Chemical Soc, 2014) Bennion, Brian J.; Eşsiz, Şebnem; Eşsiz, Şebnem; Lau, Edmond Y.; Fattebert, Jean-Luc; Emigh, Aiyana; Lightstone, Felice C.; Molecular Biology and Genetics
[Abstract Not Available]
Structural Study of Gaba Type a Receptor : the Effect of Intrasubunit Disulphide Bridges on Dynamics
(Kadir Has Üniversitesi, 2014) Ayan, Meral; Eşsiz, Şebnem; Gökhan Eşsiz, Şebnem; Molecular Biology and Genetics
In the mammalian brain the gamma-aminobutyric acid type A receptor is the most commonly expressed subtype of receptor family. Although there is a rich pharmacological activity of R, specific molecular features are still not well known. In this study, we developed a new homology model based on a recently available X-Ray structure of the glutamate-gated chloride channel. When it is compared with previous homology models of the based on lower sequence identity templates, there are three additional disulphide bridges occurring in between membrane spanning alpha helices namely two in the alpha and one in the gamma subunits. These new disulphide bridges are occurring due to the differences in the sequence alignments of template and target structures. Additionally, we performed molecular dynamics simulations with two models, one with the disulphide bridges in the transmembrane domanin, and the other without disulphide bridges. To analyze simulation results, minimum pore radius along the pore, root-mean-square deviation of proteins and root mean square fluctuation of alpha are analyzed. Finally principal component analysis of the 100 nanosecond long trajectory is calculated to compare the differences in the correlated motions of two models
Citation - WoS: 47
Citation - Scopus: 51
New Azole Derivatives Showing Antimicrobial Effects and Their Mechanism of Antifungal Activity by Molecular Modeling Studies
(Elsevier France-Editions Scientifiques Medicales Elsevier, 2017) Doğan, İnci Selin; Eşsiz, Şebnem; Saraç, Selma; Sarı, Suat; Kart, Didem; Eşsiz, Şebnem; Vural, İmran; Dalkara, Sevim; Molecular Biology and Genetics
Azole antifungals are potent inhibitors of fungal lanosterol 14 alpha demethylase (CYP51) and have been used for eradication of systemic candidiasis clinically. Herein we report the design synthesis and biological evaluation of a series of 1-phenyl/1-(4-chlorophenyl)-2-(1H-imidazol-1-yl) ethanol esters. Many of these derivatives showed fungal growth inhibition at very low concentrations. Minimal inhibition concentration (MIC) value of 15 was 0.125 mu g/mL against Candida albicans. Additionally some of our compounds such as 19 (MIC: 0.25 mu g/mL) were potent against resistant C. glabrata a fungal strain less susceptible to some first-line antifungal drugs. We confirmed their antifungal efficacy by antibiofilm test and their safety against human monocytes by cytotoxicity assay. To rationalize their mechanism of action we performed computational analysis utilizing molecular docking and dynamics simulations on the C. albicans and C. glabrata CYP51 (CACYP51 and CGCYP51) homology models we built. Leu130 and T131 emerged as possible key residues for inhibition of CGCYP51 by 19. (C) 2017 Elsevier Masson SAS. All rights reserved.
Citation - WoS: 2
Citation - Scopus: 2
Correlated conformational dynamics of the human GluN1-GluN2A type N-methyl-D-aspartate (NMDA) receptor
(SPRINGER, 2021) Eşsiz, Şebnem; Servili, Burak; Aktolun, Muhammed; Demir, Ayhan; Carpenter, Timothy S.; Servili, Burak; Core Program; Molecular Biology and Genetics
N-Methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels found in the nerve cell membranes. As a result of overexcitation of NMDARs, neuronal death occurs and may lead to diseases such as epilepsy, stroke, Alzheimer's disease, and Parkinson's disease. In this study, human GluN1- GluN2A type NMDAR structure is modeled based on the X-ray structure of the Xenopus laevis template and missing loops are added by ab-initio loop modeling. The final structure is chosen according to two different model assessment scores. To be able to observe the structural changes upon ligand binding, glycine and glutamate molecules are docked into the corresponding binding sites of the receptor. Subsequently, molecular dynamics simulations of 1.3 mu s are performed for both apo and ligand-bound structures. Structural parameters, which have been considered to show functionally important changes in previous NMDAR studies, are monitored as conformational rulers to understand the dynamics of the conformational changes. Moreover, principal component analysis (PCA) is performed for the equilibrated part of the simulations. From these analyses, the differences in between apo and ligand-bound simulations can be summarized as the following: The girdle right at the beginning of the pore loop, which connects M2 and M3 helices of the ion channel, partially opens. Ligands act like an adhesive for the ligand-binding domain (LBD) by keeping the bi-lobed structure together and consequently this is reflected to the overall dynamics of the protein as an increased correlation of the LBD with especially the amino-terminal domain (ATD) of the protein.
Loop Modeling and Molecular Dynamics Simulations of Apo and Ligand-Bound Human Glun1-Hlun2a Nmda Type Receptors
(Kadir Has Üniversitesi, 2017) Aktolun, Muhammed; Eşsiz, Şebnem; Eşsiz, Şebnem; Molecular Biology and Genetics
N-Methyl-D-Aspartate receptors (NMDARs) are glutamate-gated ion channels found in the nerve cell membranes. The functioning of the receptor is of crucial importance in consciousness and normal brain functions. As a result of overexcitation of NMDARs neuronal death occurs and may lead to diseases such as epilepsy stroke Alzheimer's and Parkinson's. Understanding the molecular mechanism and structure function relationships of the receptor might lead to discovery of new drug target mechanisms. Recently there are two intact X-ray structures available one is from Xenopus laevis and the other one is from Rattus norvegicus for GluN1-GluN2B type NMDA receptor. First both Xray structures are examined and compared for the ion channel especially by taking the general problems into consideration which arise from crystallization conditions. Human GluN1- GluN2A type NMDAR structure is modeled based on the structure of Xenopus laevis template and missing loops are added by ab-initio loop modeling. Final structure is chosen according to the model assessment scoring function. NMDAR activation requires binding of two coagonists glycine and glutamate. To be able to observe the structural changes upon ligand binding glycine and glutamate molecules are docked into the corresponding binding sites of the receptor. Subsequently Molecular Dynamics (MD) simulations of 1 microsecond are performed for both apo and ligand-bound structures. 10 structural parameters which have been considered as functionally important in previous NMDA studies are developed to understand the dynamics of the conformational changes that is associated with the function of the protein throughout the simulations. Moreover Principal Component Analysis is performed for the equilibrated part of the simulations to classify similar conformations together. in the ligand-bound simulation certain loop regions showed higher mobility. Upon ligand binding closure in LBD clamshell smaller ATD-LBD inter-domain distance and larger LBDTMD linker distance is observed in specific subunits. Opening in the bottom TMD girdle is observed for a short time. Correlated motions of the receptor in the ligand-bound simulation increased. The structure showed rotation-like motion in the apo simulation whereas slidinglike motion within the neighboring heterodimers are observed.
Citation - WoS: 1
Citation - Scopus: 1
Synthesis of New Imidazo[1,2-A]pyridine Triazole Hybrid Molecules as Potential Apoptotic Antitumor Agents
(Wiley-v C H verlag Gmbh, 2024) Halac, Fatma Albayrak; Eşsiz, Şebnem; Essiz, Sebnem; Servili, Burak; Servili, Burak; Altundas, Ramazan; Sucu, Bilgesu Onur; Kulu, Irem; Core Program; Molecular Biology and Genetics
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
Citation - WoS: 31
Citation - Scopus: 32
A Wrench in the Works of Human Acetylcholinesterase: Soman Induced Conformational Changes Revealed by Molecular Dynamics Simulations
(Public Library Science, 2015) Eşsiz, Şebnem; Eşsiz, Şebnem; Lau, Edmond Y.; Fattebert, Jean-Luc; Emigh, Aiyana; Lightstone, Felice C.; Molecular Biology and Genetics
Irreversible inactivation of human acetylcholinesterase (hAChE) by organophosphorous pesticides (OPs) and chemical weapon agents (CWA) has severe morbidity and mortality consequences. We present data from quantum mechanics/molecular mechanics (QM/MM) and 80 classical molecular dynamics (MD) simulations of the apo and soman-adducted forms of hAChE to investigate the effects on the dynamics and protein structure when the catalytic Serine 203 is phosphonylated. We find that the soman phosphonylation of the active site Ser203 follows a water assisted addition-elimination mechanism with the elimination of the fluoride ion being the highest energy barrier at 6.5 kcal/mole. We observe soman-dependent changes in backbone and sidechain motions compared to the apo form of the protein. These alterations restrict the soman-adducted hAChE to a structural state that is primed for the soman adduct to be cleaved and removed from the active site. The altered motions and resulting structures provide alternative pathways into and out of the hAChE active site. In the soman-adducted protein both side and back door pathways are viable for soman adduct access. Correlation analysis of the apo and soman adducted MD trajectories shows that the correlation of gorge entrance and back door motion is disrupted when hAChE is adducted. This supports the hypothesis that substrate and product can use two different pathways as entry and exit sites in the apo form of the protein. These alternative pathways have important implications for the rational design of medical countermeasures.
Effects of Nerve Agents on Conformational Dynamics of Acetylcholinesterase
(Kadir Has Üniversitesi, 2021) Güleşen, Sevilay; Güleşen, Sevilay; Eşsiz, Şebnem; Gökhan, Şebnem Eşsiz; Core Program; Molecular Biology and Genetics
Human acetylcholinesterase (hAChE), an essential enzyme in the central and peripheral nervous system, hydrolyses acetylcholine (ACh) at the cholinergic synapses. Organophosphorus pesticides (OPs), also called nerve agents, can inactivate the hAChE irreversibly and leads to serious morbidity (such as paralysis, cognitive deficiencies, and seizures) and even mortality consequences based on the amount of exposure and rapidness of treatment. Therefore, understanding the inhibition mechanism of hAChE by OPs, such as soman and sarin, is critical since it may guide developing a new and efficient treatment for poisoning by the nerve agents. The effects of soman inhibition on the dynamics of the hAChE were investigated in comparison with the results of the molecular dynamics study of the apo form and another OP adducted, i.e. soman adducted, form of hAChE in 2005. To understand the changes in the protein structure of hAChE after binding soman, 40 MD data were published. In this thesis, we aimed to find how sarin phosphorylation of the active site Ser203 residue of the hAChE affects the protein dynamics and to compare the result with the previously discovered results of the apo and soman-adducted hAChE. First, 40 classical MD simulations for the sarin adducted hAChE were run with the exact parameters of the apo and soman-adducted hAChE simulations. The sarin adducted hAChE was used for the MD simulations. Resulting trajectories were analyzed with RMSD analysis, principal component analysis (PCA), and K-means clustering algorithm calculations to understand the differences between collective motions of the apo, soman adducted, and sarin adducted hAChE. According to the results, the sarin molecule has an alternative pathway for entering and leaving from the active site of the hAChE like the soman molecule. The back door area when it is calculated from the backbone atoms versus the sidechain atoms shows a significant different behavior. The backbone atoms calculation of the sarin-adducted gives similar results with the apo simulation. However, there is a significant third peak at much larger value observed in the calculation of the sarin-adducted sidechain. That might be an alternative pathway for entrance to the molecule. Also, the gorge entrance and back door motion correlation is affected when hAChE is adducted by sarin, depending on correlation analysis. This disruption and the previous mentioned above area results support the hypothesis about alternative pathways for entrance and exit in the protein. All these motions and alternative pathways are critical for the development of the treatment of sarin poisoning. Keywords: Molecular dynamic simulation, acetylcholinesterase, sarin, soman, principal component analysis
Modelling of C-Terminal Tail of Human Sting and Its Interaction With\rtank-Binding Kinase 1
(2022) Masrı, Rahaf Ata Ouda Al; Eşsiz, Şebnem; Bıda, Hajara Audu; Eşsiz, Şebnem; Molecular Biology and Genetics
Stimulator of interferon genes (STING) plays a significant role in a cell’s intracellular defense against pathogens or selfDNA by inducing inflammation or apoptosis through a pathway known as cGAS-cGAMP-STING. STING uses one of its domains, the\rC-terminal tail (CTT) to recruit the members of the pathway. However, the structure of this domain has not been solved experimentally.\rSTING conformation is open and more flexible when inactive. When STING gets activated by cGAMP, its conformation changes to a\rclosed state covered by 4 beta-sheets over the binding site. This conformational change leads to its binding to Tank-binding kinase 1\r(TBK1). TBK1 then phosphorylates STING aiding its entry to the cell’s nucleus.\rIn this study, we focused on the loop modeling of the CTT domain in both the active and inactive STING conformations. After the\rmodeling step, the active and inactive STING structures were docked to one of the cGAS-cGAMP-STING pathway members, TBK1,\rto observe the differences of binding modes. CTT loop stayed higher in the active structure, while all the best-scored models, active or\rinactive, ended up around the same position with respect to TBK1. However, when the STING poses are compared with the cryo-EM\rimage of the complex structure, the models in the active structure chain B displayed closer results to the complex structure.