Person: MUTLU, ÖZAL
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MUTLU
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ÖZAL
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Publication Metadata only Computational insight into the phthalocyanine-DNA binding via docking and molecular dynamics simulations(ELSEVIER SCI LTD, 2018) MUTLU, ÖZAL; Ozalp, Lalehan; Erdem, Safiye Sag; Yuce-Dursun, Basak; Mutlu, Ozal; Ozbil, MehmetPhthalocyanines are considered as good DNA binders, which makes them promising anti-tumor drug leads. The purpose of this study is to investigate the interactions between DNA and quaternary metallophthalocyanine derivatives (Q-MPc) possessing varying metals (M = Zn, Ni, Cu, Fe, Mg and Ca) by molecular docking since there seems to be a lack of information in the literature regarding this issue. In this direction, Autodock Vina and Molegro Virtual Docker programs were employed. Autodock Vina results reveal that each Q-MPc derivative binds to DNA strongly with similar binding energies and almost identical binding modes. They bind to the grooves of DNA by constituting favorable interactions between phosphate groups of DNA and Q-MPcs. Although changing the metal has no significant effect on binding, presence of quaternary amine substituents increases the binding constant K-b by about 2-fold comparing to the core Pc (ZnPc). Contrary to Autodock Vina, the calculated Molegro Virtual Docker binding scores have been more diverse indicating that the scoring function of Molegro is better in differentiating these metals. Despite the fact that Molegro is superior to Autodock Vina in terms of metal characterization, Autodock Vina and Molegro exhibit similar binding sites for the studied metallophthalocyanines. We propose that Q-MPc derivatives designed in this study are promising anti-tumor lead compounds since they tightly bind to DNA with considerably high K-b values. Cationic substituents and presence of metal have both positive effects on DNA binding which is critical for designing DNA-active drugs. Additional calculations employing molecular dynamics (MD) simulations verified the stability of Q-MPc-DNA complexes which remained in contact after 20 ns via attractive interactions mainly between DNA backbone and the Pc metal center.Publication Metadata only Biochemical and in silico Characterization of Recombinant L-Lactate Dehydrogenase of Theileria annulata(HUMANA PRESS INC, 2016) MUTLU, ÖZAL; Nural, Belma; Erdemir, Aysegul; Mutlu, Ozal; Yakarsonmez, Sinem; Danis, Ozkan; Topuzogullari, Murat; Turgut-Balik, DilekTheileria annulata is a parasite that causes theileriosis in cattle. Reports about drug resistance made essential to develop new drug. LDH of Theileria schizonts is the vital enzyme for its anaerobic metabolism. TaLDH gene was first cloned into pGEM-T cloning vector with two introns in our previous study. Here we report cloning of TaLDH without introns into pLATE 31 vector in E. coli BL21(DE3). Protein was in an inactive form. Two mutations were fixed to express the active protein. Protein was purified by affinity chromatography and evaluated by SDS-PAGE and size exclusion chromatography. Optimum pH of enzyme was performed in pH 7.5, and enzyme was stabilized at 20-40 A degrees C. Enzyme kinetics of recombinant TaLDH were found to be in the direction of pyruvate to lactate K (m) 0.1324 and K (i) 4.295 mM, k (cat) , 44.55/s and k (cat) /K (m) , 3.3693 x 10(5)/M/s. 3D structure of TaLDH was predicted, and possible drug binding sites were determined by homology modelling.Publication Open Access Experimentation and analysis of powder injection molded Ti10Nb10Zr alloy: a promising candidate for electrochemical and biomedical application(ELSEVIER, 2019-11) GÜLSOY, HAMİT ÖZKAN; Yemisci, Isil; Mutlu, Ozal; Gulsoy, Nagihan; Kunal, Kate; Atre, Sundar; Gulsoy, H. OzkanThis paper describes the microstructural, mechanical and corrosion properties of injection molded Ti10Nb10Zr alloys. T10Nb10Zr powder was injection molded with wax-based binder. The critical powder loading for injection molding was 55 vol% for feedstock. Binder debinding was performed in solvent and thermal method. After debinding the samples were sintered at different temperatures and times in vacuum atmosphere (10-5 mbar) to obtain fully dense parts. Metallographic studies were conducted to determine the extent of densification and the corresponding microstructural changes. The electrochemical property and biocompatibility of the sintered samples were performed electrochemically, by selfbody -fluid immersion tests and cell culture experiments. The results show that Ti10Nb10Zr alloys could be sintered to a maximum 99% of theoretical density. Maximum ultimate tensile strength, elongation and hardness obtained were 748 MPa, 14.3 and 114 HRB respectively at 1500 degrees C for 3 h. Additionally, the sintered i10Nb10Zr alloys exhibited high mechanical and corrosion properties in a physiological environment. (C) 2019 The Author. Published by Elsevier B.V.Publication Metadata only Effect of Zr, Nb and Ti addition on injection molded 316L stainless steel for bio-applications: Mechanical, electrochemical and biocompatibility properties(ELSEVIER SCIENCE BV, 2015) GÜLSOY, HAMİT ÖZKAN; Gulsoy, H. Ozkan; Pazarlioglu, Serdar; Gulsoy, Nagihan; Gundede, Busra; Mutlu, OzalThe research investigated the effect of Zr, Nb and Ti additions on mechanical, electrochemical properties and biocompatibility of injection molded 316L stainless steel. Addition of elemental powder is promoted to get high performance of sintered 316L stainless steels. The amount of additive powder plays a role in determining the sintered microstructure and all properties. In this study, 316L stainless steel powders used with the elemental Zr, Nb and Ti powders. A feedstock containing 62.5 wt% powders loading was molded at different injection molded temperature. The binders were completely removed from molded components by solvent and thermal debinding at different temperatures. The debinded samples were sintered at 1350 degrees C for 60 min. Mechanical, electrochemical property and biocompatibility of the sintered samples were performed mechanical, electrochemical, SBF immersion tests and cell culture experiments. Results of study showed that sintered 316L and 316L with additives samples exhibited high corrosion properties and biocompatibility in a physiological environment. (C) 2015 Elsevier Ltd. All rights reserved.Publication Metadata only Functional analyses of dipeptide and pentapeptide insertions on Theileria annulata enolase by site-directed mutagenesis and in silico approaches(ELSEVIER SCIENCE BV, 2019) MUTLU, ÖZAL; Yakarsonmez, Sinem; Cengiz, Ebru Cayir; Mutlu, Ozal; Turgut-Balik, DilekTheileria annulata enolase (TaENO) could be assessed as a druggable target for tropical theileriosis treatment. The parasite enzyme plays an important role in many cellular functions and carries some structural differences like dipeptide (262EK263) and pentapeptide ((103)EWGYC(107)) insertions from the host enzyme, Bos taurus enolase. In this study, the functional effects of these insertions on TaENO activity were analyzed by in vitro site-directed mutagenesis and in silico molecular docking analyses for the first time in the literature. In vitro results showed that, although the deletion of the pentapeptide insertion (TaENO Delta EWGYC) reduced the enzyme activity slightly, the removal of the dipeptide insertion (TaENO Delta EK) halted it. Also, molecular docking results revealed that the deletion of these insertions affected the substrate binding affinity of the mutant enzymes. The active site of TaENO Delta EK exhibited a small decrease of substrate binding affinity compared to the active site of TaENO Delta EWGYC relative to the wild type TaENO. Although we conclude that both regions could be evaluated as possible drug-binding sites to inhibit TaENO in further studies, these results indicate that the dipeptide insertion could be a more promising drug binding site than the pentapeptide insertion.Publication Metadata only Novel hydroxyapatite/graphene oxide/collagen bioactive composite coating on Ti16Nb alloys by electrodeposition(ELSEVIER SCIENCE BV, 2019) GÜLSOY, HAMİT ÖZKAN; Yilmaz, Eren; Cakiroglu, Bekir; Gokce, Azim; Findik, Fehim; Gulsoy, H. Ozkan; Gulsoy, Nagihan; Mutlu, Ozal; Ozacar, MahmutA novel implant coating material containing graphene oxide (GO) and collagen (COL), and hydroxyapatite (HA) was fabricated with the aid of tannic acid by electrodeposition. The surface of Ti16Nb alloy was subjected to anodic oxidation, and then HA-GO coating was applied to Ti16Nb surface by cathodic method. Then, COL was deposited on the surface of the HA-GO coating by the biomimetic method. HA, HA-GO, HA-GO-COL coatings on the surface of the Ti16Nb alloy have increased the corrosion resistance by the formation of a barrier layer on the surface. For HA-GO-COL coating, the highest corrosion resistance is obtained due to the compactness and homogeneity of the coating structure. The contact angle of the bare Ti16Nb is approximately 65 degrees, while the contact angle of the coated samples is close to 0 degrees. Herein, the increased surface wettability is important for cell adhesion. The surface roughness of the uncoated Ti16Nb alloy was between 1 and 3 mu m, while the surface roughness of the coated surfaces was measured between 20 and 110 mu m. The contact between the bone and the implant has been improved. Graphene oxide-containing coatings have improved the antibacterial properties compared to the GO-free coating using S. aureus. The hardness and elastic modulus of the coatings were measured by the nanoindentation test, and the addition of GO and collagen to the HA coating resulted in an increase in strength. The addition of GO to the HA coating reduced the viability of 3 T3 fibroblast cells, whereas the addition of collagen to HA-GO coat increased the cell adhesion and viability.Publication Metadata only Single Mutation in Shine-Dalgarno-Like Sequence Present in the Amino Terminal of Lactate Dehydrogenase of Plasmodium Effects the Production of an Eukaryotic Protein Expressed in a Prokaryotic System(HUMANA PRESS INC, 2013) MUTLU, ÖZAL; Cicek, Mustafa; Mutlu, Ozal; Erdemir, Aysegul; Ozkan, Ebru; Saricay, Yunus; Turgut-Balik, DilekOne of the most important step in structure-based drug design studies is obtaining the protein in active form after cloning the target gene. In one of our previous study, it was determined that an internal Shine-Dalgarno-like sequence present just before the third methionine at N-terminus of wild type lactate dehydrogenase enzyme of Plasmodium falciparum prevent the translation of full length protein. Inspection of the same region in P. vivax LDH, which was overproduced as an active enzyme, indicated that the codon preference in the same region was slightly different than the codon preference of wild type PfLDH. In this study, 5'-GGAGGC-3' sequence of P. vivax that codes for two glycine residues just before the third methionine was exchanged to 5'-GGAGGA-3', by mimicking P. falciparum LDH, to prove the possible effects of having an internal SD-like sequence when expressing an eukaryotic protein in a prokaryotic system. Exchange was made by site-directed mutagenesis. Results indicated that having two glycine residues with an internal SD-like sequence (GGAGGA) just before the third methionine abolishes the enzyme activity due to the preference of the prokaryotic system used for the expression. This study emphasizes the awareness of use of a prokaryotic system to overproduce an eukaryotic protein.Publication Metadata only Effects of residue deletions from pentapeptide insertion of enzyme lactate dehydrogenase from Plasmodium vivax(CURRENT BIOLOGY LTD, 2011) MUTLU, ÖZAL; Mutlu, Ozal; Turgut-Balik, DilekPublication Metadata only Functional and structural characterization of the pentapeptide insertion of Theileria annulata lactate dehydrogenase by site-directed mutagenesis, comparative modeling and molecular dynamics simulations(ELSEVIER SCIENCE INC, 2017) MUTLU, ÖZAL; Erdemir, Aysegul; Mutlu, OzalLactate dehydrogenase (LDH) is an important metabolic enzyme in glycolysis and it has been considered as the main energy source in many organisms including apicomplexan parasites. Differences at the active site loop of the host and parasite LDH's makes this enzyme an attractive target for drug inhibitors. In this study, five amino acid insertions in the active site pocket of Theileria annulata LDH (TaLDH) were deleted by PCR-based site-directed mutagenesis, expression and activity analysis of mutant and wild type TaLDH enzymes were performed. Removal of the insertion at the active site loop caused production of an inactive enzyme. Furthermore, structures of wild and mutant enzymes were predicted by comparative modeling and the importance of the insertions at the active site loop were also assigned by molecular docking and dynamics simulations in order to evaluate essential role of this loop for the enzymatic activity. Pentapeptide insertion removal resulted in loss of LDH activity due to deletion of Trp96 and conformational change of Arg98 because of loop instability. Analysis of wild type and mutant enzymes with comparative molecular dynamics simulations showed that the fluctuations of the loop residues increase in mutant enzyme. Together with in silico studies, in vitro results revealed that active site loop has a vital role in the enzyme activity and our findings promise hope for the further drug design studies against theileriosis and other apicomplexan parasite diseases. (C) 2017 Elsevier Inc. All rights reserved.Publication Metadata only Comprehensive structural analysis of the open and closed conformations of Theileria annulata enolase by molecular modelling and docking(ELSEVIER SCI LTD, 2016) MUTLU, ÖZAL; Mutlu, Ozal; Yakarsonmez, Sinem; Sariyer, Emrah; Danis, Ozkan; Yuce-Dursun, Basalt; Topuzogullari, Murat; Akbulut, Ekrem; Turgut-Balik, DilekTheileria annulata is an apicomplexan parasite which is responsible for tropical theileriosis in cattle. Due to resistance of T. annulata against commonly used antitheilerial drug, new drug candidates should be identified urgently. Enolase might be a druggable protein candidate which has an important role in glycolysis, and could also be related to several cellular functions as a moonlight protein. In this study; we have described three-dimensional models of open and closed conformations of T. annulata enolase by homology modeling method for the first time with the comprehensive domain, active site and docking analyses. Our results show that the enolase has similar folding patterns within enolase superfamily with conserved catalytic loops and active site residues. We have described specific insertions, possible plasminogen binding sites, electrostatic potential surfaces and positively charged pockets as druggable regions in T. annulate enolase. (C) 2016 Elsevier Ltd. All rights reserved.