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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/3
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Publication Metadata only Characterization and comparison of insulinoma tumor model and pancreatic damage caused by the tumor, and identification of possible markers(Springer Science and Business Media B.V., 2024) Karatug Kacar, Ayse; Aylar, Dilara; Celikten, Mert; Bolkent, Sehnaz; Bulutay, Pınar; School of MedicineInsulinoma is a neuroendocrine tumor. It arises from the uncontrolled proliferation of pancreatic β cells. In this study, we created an insulinoma tumor model in nude mice. INS-1 cells were injected in two different ways, subcutaneously (S.C.) or intraperitoneally (I.P.). Body weight, tumor weight, and size were measured. ELISA kits were used analyze to Glucose, insulin, and CA19-9 levels in serum, pancreas, and tumor tissues. KCNN4, KCNK1, GLUT2, IR, HSP70, HSF1, and HSP90 levels were analyzed by western blotting of membrane and/or cytosolic fractions of tumor and pancreas tissue. Tumor formation occurred in nude mice, but it did not occur in Wistar albino rats. The tumor has neuroendocrine cell morphology. Insulin and CA19-9 levels increased in pancreas tissue. In tumor tissue, KCNN4 levels were higher in both membrane and cytosolic fractions, while KCNK1 levels were lower in the membrane fraction of the S.C. group. HSP70 levels were also lower in the S.C. group. In pancreas tissue, KCNK1 levels were lower in the membrane fraction of the S.C. and I.P. groups. GLUT2 levels increased in both groups according to the control group, while IR levels decreased in the S.C. group compared to the control group. However, HSF1 levels increased in the I.P. group, while HSP90 decreased in the S.C. group in pancreatic tissues. The S.C. group is a more suitable insulinoma tumor model. KCNN4, KCNK1, and HSP70 proteins may be important biomarkers in the diagnosis and treatment of insulinoma.Publication Metadata only The introduction of hydrogen bond and hydrophobicity effects into the rotational isomeric states model for conformational analysis of unfolded peptides(Iop Publishing Ltd, 2009) N/A; Department of Mechanical Engineering; Department of Chemical and Biological Engineering; Engin, Özge; Sayar, Mehmet; Erman, Burak; Master Student; Faculty Member; Faculty Member; Department of Mechanical Engineering; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering, College of Engineering; College of Engineering; N/A; 109820; 179997Relative contributions of local and non-local interactions to the unfolded conformations of peptides are examined by using the rotational isomeric states model which is a Markov model based on pairwise interactions of torsion angles. the isomeric states of a residue are well described by the Ramachandran map of backbone torsion angles. the statistical weight matrices for the states are determined by molecular dynamics simulations applied to monopeptides and dipeptides. Conformational properties of tripeptides formed from combinations of alanine, valine, tyrosine and tryptophan are investigated based on the Markov model. Comparison with molecular dynamics simulation results on these tripeptides identifies the sequence-distant long-range interactions that are missing in the Markov model. these are essentially the hydrogen bond and hydrophobic interactions that are obtained between the first and the third residue of a tripeptide. a systematic correction is proposed for incorporating these long-range interactions into the rotational isomeric states model. Preliminary results suggest that the Markov assumption can be improved significantly by renormalizing the statistical weight matrices to include the effects of the long-range correlations.Publication Metadata only Membrane-associated Ras dimers are isoform-specific: K-Ras dimers differ from H-Ras dimers(Portland Press Ltd, 2016) Nussinov, Ruth; Jang, Hyunbum; N/A; Department of Chemical and Biological Engineering; Department of Computer Engineering; Muratçıoğlu, Serena; Keskin, Özlem; Gürsoy, Attila; PhD Student; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Department of Computer Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; 26605; 8745Are the dimer structures of active Ras isoforms similar? This question is significant since Ras can activate its effectors as a monomer; however, as a dimer, it promotes Raf's activation and MAPK (mitogen-activated protein kinase) cell signalling. In the present study, we model possible catalytic domain dimer interfaces of membrane-anchored GTP-bound K-Ras4B and H-Ras, and compare their conformations. The active helical dimers formed by the allosteric lobe are isoform-specific: K-Ras4B-GTP favours the alpha 3 and alpha 4 interface; H-Ras-GTP favours alpha 4 and alpha 5. Both isoforms also populate a stable beta-sheet dimer interface formed by the effector lobe; a less stable beta-sandwich interface is sustained by salt bridges of the beta-sheet side chains. Raf's high-affinity beta-sheet interaction is promoted by the active helical interface. Collectively, Ras isoforms' dimer conformations are not uniform; instead, the isoform-specific dimers reflect the favoured interactions of the HVRs (hypervariable regions) with cell membrane microdomains, biasing the effector-binding site orientations, thus isoform binding selectivity.Publication Metadata only Identification and characterization of a new class of (6−4) photolyase from Vibrio cholerae(Amer Chemical Soc, 2019) Ozcelik, Gozde; Ozturk, Nuri; N/A; N/A; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Dikbaş, Uğur Meriç; Tardu, Mehmet; Gül, Şeref; Barış, İbrahim; Kavaklı, İbrahim Halil; Master Student; PhD Student; Researcher; Teaching Faculty; Faculty Member; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Sciences; College of Engineering; N/A; N/A; N/A; 111629; 40319Light is crucial for many biological activities of most organisms, including vision, resetting of circadian rhythm, photosynthesis, and DNA repair. The cryptochrome/photolyase family (CPF) represents an ancient group of UV-A/blue light sensitive proteins that perform different functions such as DNA repair, circadian photoreception, and transcriptional regulation. The CPF is widely distributed throughout all organisms, including marine prokaryotes. The bacterium Vibrio cholerae was previously shown to have a CPD photolyase that repairs UV-induced thymine dimers and two CRY-DASHs that repair UV-induced single-stranded DNA damage. Here, we characterize a hypothetical gene Vca0809 encoding a new member of CPF in this organism. The spectroscopic analysis of the purified protein indicated that this enzyme possessed a catalytic cofactor, FAD, and photoantenna chromophore 6,7-dimethyl 8-ribityllumazin. With a slot blot-based DNA repair assay, we showed that it possessed (6-4) photolyase activity. Further phylogenetic and computational analyses enabled us to classify this gene as a member of the family of iron-sulfur bacterial cryptochromes and photolyases (FeS-BCP). Therefore, we named this gene Vc(6-4) FeS-BCP.Publication Metadata only Molecular dynamics simulations provide molecular insights into the role of HLA-B51 in Behcet's disease pathogenesis(2020) Gür, Mert; Gölcük, Mert; Gül, Ahmet; Department of Chemical and Biological Engineering; Erman, Burak; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 179997Behcet's disease is an inflammatory disorder of unknown etiology. Genetic tendency has an important role in its pathogenesis, and HLA-B51, a class I MHC antigen, has been recognized as the strongest susceptibility factor for Behcet's disease. Despite the confirmation of the association of HLA-B51 with Behcet's disease in different populations, its pathogenic mechanisms remain elusive. HLA-B51 differs in only two amino acids from HLA-B52, other split antigen of HLA-B5, which is not associated with Behcet's disease. These two amino acids are located in the B pocket of the antigen-binding groove, which occupies the second amino acids of the bound peptides. To understand the nature of the HLA-peptide interactions, differences in structure and dynamics of two HLA alleles were investigated by molecular dynamics simulations using YAYDGKDYI, LPRSTVINI, and IPYQDLPHL peptides. For HLA-B51, all bound peptides fluctuated to larger extent than HLA-B52. Free energy profiles of unbinding process for YAYDGKDYI by steered molecular dynamics simulations showed that unbinding from HLA-B52 results in greater free energy differences than HLA-B51. These results suggest the possibility of an instability of HLA-B51 associated with the repertoire of peptides, and this finding may provide significant insight to its pathogenic role in Behcet's disease.Publication Metadata only Quantification of interactions among circadian clock proteins via surface plasmon resonance(Wiley, 2014) N/A; N/A; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Kepsütlü, Burcu; Kızılel, Rıza; Kızılel, Seda; Master Student; Researcher; Faculty Member; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; 114475; 28376Circadian clock is an internal time keeping system recurring 24h daily rhythm in physiology and behavior of organisms. Circadian clock contains transcription and translation feedback loop involving CLOCK/NPaS2, BMaL1, Cry1/2, and Per1/2. in common, heterodimer of CLOCK/NPaS2 and BMaL1 binds to EBOX element in the promoter of Per and Cry genes in order to activate their transcription. CRY and PER making heterodimeric complexes enter the nucleus in order to inhibit their own BMaL1-CLOCK-activated transcription. the aim of this study was to investigate and quantify real-time binding affinities of clock proteins among each other on and off DNa modes using surface plasmon resonance. the pairwise interaction coefficients among clock proteins, As well as interaction of PER2, CRY2, and PER2:CRY2 proteins with BMaL1:CLOCK complex in the presence and absence of EBOX motif have been investigated via analysis of surface plasmon resonance data with pseudo first-order reaction kinetics approximation and via nonlinear regression curve fitting. the results indicated that CRY2 and PER2, BMaL1, and CLOCK proteins form complexes in vitro and that PER2, CRY2 and PER2:CRY2 complex have similar affinities toward BMaL1:CLOCK complex. CRY2 protein had the highest affinity toward EBOX complex, whereas PER2 and CRY2:PER2 complexes displayed low affinity toward EBOX complex. the quantification of the interaction between clock proteins is critical to understand the operation mechanism of the biological clock and to address the behavioral and physiological disorders, and it will be useful for the design of new drugs toward clock-related diseases.Publication Metadata only Characterization and prediction of protein interfaces to infer protein-protein interaction networks(Bentham Science Publ Ltd, 2008) N/A; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Department of Computer Engineering; Keskin, Özlem; Tunçbağ, Nurcan; Gürsoy, Attila; Faculty Member; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Department of Computer Engineering; College of Engineering; College of Engineering; College of Engineering; 26605; 245513; 8745Complex protein-protein interaction networks govern biological processes in cells. Protein interfaces are the sites where proteins physically interact. Identification and characterization of protein interfaces will lead to understanding how proteins interact with each other and how they are involved in protein-protein interaction networks. What makes a given interface bind to different proteins; how similar/different the interactions in proteins are some key questions to be answered. Enormous amount of protein structures and experimental protein-protein interactions data necessitate advanced computational methods for analyzing and inferring new knowledge. Interface prediction methods use a wide range of sequence, structural and physico-chemical characteristics that distinguish interface residues from non-interface surface residues. Here, we present a review focusing on the characteristics of interfaces and the current status of interface prediction methods.Publication Metadata only Does prolonged radiofrequency radiation emitted from wi-fi devices induce dna damage in various tissues of rats?(Elsevier, 2016) Akdag, Mehmet Zulkuf; Dasdag, Suleyman; Canturk, Fazile; Karabulut, Derya; Caner, Yusuf; N/A; Adalıer, Nur; Undergraduate Student; School of Medicine; N/AWireless internet (Wi-Fi) providers have become essential in our daily lives, as wireless technology is evolving at a dizzying pace. Although there are different frequency generators, one of the most commonly used Wi-Fi devices are 2.4 GHz frequency generators. These devices are heavily used in all areas of life but the effect of radiofrequency (RF) radiation emission on users is generally ignored. Yet, an increasing share of the public expresses concern on this issue. Therefore, this study intends to respond to the growing public concern. The purpose of this study is to reveal whether long term exposure of 2.4 GHz frequency RF radiation will cause DNA damage of different tissues such as brain, kidney, liver, and skin tissue and testicular tissues of rats. The study was conducted on 16 adult male Wistar Albino rats. The rats in the experimental group (n = 8) were exposed to 2.4 GHz frequency radiation for over a year. The rats in the sham control group (n = 8) were subjected to the same experimental conditions except the Wi-Fi generator was turned off. After the exposure period was complete the possible DNA damage on the rat's brain, liver, kidney, skin, and testicular tissues was detected through the single cell gel electrophoresis assay (comet) method. The amount of DNA damage was measured as percentage tail DNA value. Based on the DNA damage results determined by the single cell gel electrophoresis (Comet) method, it was found that the% tail DNA values of the brain, kidney, liver, and skin tissues of the rats in the experimental group increased more than those in the control group. The increase of the DNA damage in all tissues was not significant (p > 0.05). However the increase of the DNA damage in rat testes tissue was significant (p < 0.01). In conclusion, long-term exposure to 2.4GHz RF radiation (Wi-Fi) does not cause DNA damage of the organs investigated in this study except testes. The results of this study indicated that testes are more sensitive organ to RF radiation.Publication Metadata only Oxidative stress-A direct bridge to central nervous system homeostatic dysfunction and Alzheimer's disease(Wiley, 2022) N/A; Anwar, Mai; Other; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; N/ANeurologists have highly observed a frequent increasing number of elderly patients with Alzheimer's disease (AD) without any relevant evidence of any genetic or known AD-linked predisposing factors in the past few years. Those patients are characterized by continuous and irreversible neuron cells loss along with declined cognitive functions. Numerous studies have suggested that the exaggerated release of reactive oxygen species (ROS) within the brain may develop late-onset neurodegenerative disorders, especially AD-neuroinflammatory type. However, the central nervous system is vitally linked with whole-brain chemical integrity and its related healthy state, the cascade by which ROS may result in AD's development has not been highly justified or even maintained. It is widely known that the brain consumes a vast amount of oxygen and is characterized by being rich in lipid polyunsaturated fatty acids content, explaining why it is a prone region to oxidative stress (OS) and ROS damage. The formed OS-AD cytoskeletal protein aggregates can be considered a main predisposing factor for amyloid-beta (A beta) hallmarks precipitation. Herein, this review aims to provide a detailed information on how oxidative stress can play a pathogenic role in activating damage-associated molecular patterns (DAMPs)-related toll-like receptor-4 inflammatory (TLR-4) cascades resulting in the deposition of A beta hallmarks in brain tissues ending with irreversible cognitive dysfunction. It also explains how microglia can be activated via ROS, which may significantly release several pro-inflammatory cascades ending with general brain atrophy. Furthermore, different types of suggested antioxidant therapies will be discussed to combat AD-related pathological disorders and hallmarks.Publication Metadata only Relationships between ligand binding sites, protein architecture and correlated paths of energy and conformational fluctuations(Iop Publishing Ltd, 2011) Department of Chemical and Biological Engineering; Erman, Burak; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 179997The statistical thermodynamics basis of energy and residue position fluctuations is explained for native proteins. The protein and its surroundings are treated as a canonical system with emphasis on the effects of energy exchange between the two. Fluctuations of the energy are related to fluctuations of residue positions, which in turn are related to the connectivity matrix of the protein, thus establishing a connection between energy fluctuation pathways and protein architecture. The model gives the locations of hotspots for ligand binding and identifies the pathways of energy conduction within the protein. Results are discussed in terms of two sets of models, the BPTI and 12 proteins that contain the PDZ domain. A possible use of the model for determining functionally similar domains in a diverse set of proteins is pointed out.
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