Researcher:
Kavaklı, İbrahim Halil

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İbrahim Halil

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Kavaklı

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Now showing 1 - 10 of 84
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    Proteome analysis of the circadian clock protein PERIOD2
    (Wiley, 2022) Gül, Hüseyin; Selvi, Saba; Yılmaz, Fatma; Özçelik, Gözde; Olfaz-Aslan, Senanur; Yazan, Şeyma; Tiryaki, Büşra; Gül, Şeref; Öztürk, Nuri; N/A; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; Yurtseven, Ali; Kavaklı, İbrahim Halil; Master Student; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of Engineering; College of Sciences; N/A; 40319; 105301
    Circadian rhythms are a series of endogenous autonomous 24-h oscillations generated by the circadian clock. At the molecular level, the circadian clock is based on a transcription-translation feedback loop, in which BMAL1 and CLOCK transcription factors of the positive arm activate the expression of CRYPTOCHROME (CRY) and PERIOD (PER) genes of the negative arm as well as the circadian clock-regulated genes. There are three PER proteins, of which PER2 shows the strongest oscillation at both stability and cellular localization level. Protein-protein interactions (PPIs) or interactome of the circadian clock proteins have been investigated using classical methods such as two-dimensional gel electrophoresis, immunoprecipitation-coupled mass spectrometry, and yeast-two hybrid assay where the dynamic and weak interactions are difficult to catch. To identify the interactome of PER2 we have adopted proximity-dependent labeling with biotin and mass spectrometry-based identification of labeled proteins (BioID). In addition to known interactions with such as CRY1 and CRY2, we have identified several new PPIs for PER2 and confirmed some of them using co-immunoprecipitation technique. This study characterizes the PER2 protein interactions in depth, and it also implies that using a fast BioID method with miniTurbo or TurboID coupled to other major circadian clock proteins might uncover other interactors in the clock that have yet to be discovered.
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    Transcriptional regulation of the starch synthases isoforms in the leaf and the stem under long and short photoperiod in lentil
    (Wiley-Blackwell, 2014) Gercek, Y. C.; Oz, G. Cevahir; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Barış, İbrahim; Kavaklı, İbrahim Halil; Teaching Faculty; Faculty Member; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; College of Sciences; College of Engineering; 111629; 40319
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    Classification of cytochrome P450 inhibitors with respect to binding free energy and pIC50 using common molecular descriptors
    (Amer Chemical Soc, 2009) N/A; Department of Chemical and Biological Engineering; Department of Industrial Engineering; Dağlıyan, Onur; Kavaklı, İbrahim Halil; Türkay, Metin; Master Student; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Department of Industrial Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; 40319; 24956
    Virtual screening of chemical libraries following experimental assays of drug candidates is a common procedure in structure based drug discovery. However, the relationship between binding free energies and biological activities (pIC(50)) of drug candidates is sfill an unsolved issue that limits the efficiency and speed of drug development processes. In this study, the relationship between them is investigated based on a common molecular descriptor set for human cytochrome P450 enzymes (CYPs). CYPs play an important role in drug-drug interactions, drug metabolism, and toxicity. Therefore, in silico prediction of CYP inhibition by drug candidates is one of the major considerations in drug discovery. The combination of partial leastsquares regression (PLSR) and a variety of classification algorithms were employed by considering this relationship as a classification problem. Our results indicate that PLSR with classification is a powerful tool to predict more than one output such as binding free energy and pIC(50) simultaneously. PLSR with mixedinteger linear programming based hyperboxes predicts the binding free energy and pIC(50) with a mean accuracy of 87.18% (min: 81.67% max: 97.05%) and 88.09% (min: 79.83% max: 92.90%), respectively, for the cytochrome p450 superfamily using the common 6 molecular descriptors with a 10-fold cross- val idati on.
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    Diurnal changes in capecitabine clock-controlled metabolism enzymes are responsible for its pharmacokinetics in male mice
    (SAGE Publications Inc., 2023) Akyel Y.K.; Öztürk Civelek D.; Öztürk Seyhan N.; Gul S.; Gazioglu I.; Pala Kara Z.; Lévi F.; Okyar A.; Department of Chemical and Biological Engineering; Kavaklı, İbrahim Halil; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 40319
    The circadian timing system controls absorption, distribution, metabolism, and elimination processes of drug pharmacokinetics over a 24-h period. Exposure of target tissues to the active form of the drug and cytotoxicity display variations depending on the chronopharmacokinetics. For anticancer drugs with narrow therapeutic ranges and dose-limiting side effects, it is particularly important to know the temporal changes in pharmacokinetics. A previous study indicated that pharmacokinetic profile of capecitabine was different depending on dosing time in rat. However, it is not known how such difference is attributed with respect to diurnal rhythm. Therefore, in this study, we evaluated capecitabine-metabolizing enzymes in a diurnal rhythm-dependent manner. To this end, C57BL/6J male mice were orally treated with 500 mg/kg capecitabine at ZT1, ZT7, ZT13, or ZT19. We then determined pharmacokinetics of capecitabine and its metabolites, 5′-deoxy-5-fluorocytidine (5′DFCR), 5′-deoxy-5-fluorouridine (5′DFUR), 5-fluorouracil (5-FU), in plasma and liver. Results revealed that plasma Cmax and AUC0-6h (area under the plasma concentration-time curve from 0 to 6 h) values of capecitabine, 5′DFUR, and 5-FU were higher during the rest phase (ZT1 and ZT7) than the activity phase (ZT13 and ZT19) (p < 0.05). Similarly, Cmax and AUC0-6h values of 5′DFUR and 5-FU in liver were higher during the rest phase than activity phase (p < 0.05), while there was no significant difference in liver concentrations of capecitabine and 5′DFCR. We determined the level of the enzymes responsible for the conversion of capecitabine and its metabolites at each ZT. Results indicated the levels of carboxylesterase 1 and 2, cytidine deaminase, uridine phosphorylase 2, and dihydropyrimidine dehydrogenase (p < 0.05) are being rhythmically regulated and, in turn, attributed different pharmacokinetics profiles of capecitabine and its metabolism. This study highlights the importance of capecitabine administration time to increase the efficacy with minimum adverse effects.
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    Structure based drug design for insulin degrading enzyme (IDE)
    (AICHE, 2010) Department of Industrial Engineering; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Türkay, Metin; Kızılel, Seda; Kavaklı, İbrahim Halil; Dağlıyan, Onur; Dağyıldız, Ezgi; Çakır, Bilal; Faculty Member; Faculty Member; Faculty Member; Master Student; PhD Student; PhD Student; Department of Industrial Engineering; Department of Chemical and Biological Engineering; College of Engineering; College of Engineering; College of Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; 24956; 28376; 40319; N/A; N/A; N/A
    Insulin-degrading enzyme (IDE) is an allosteric Zn +2 metalloprotease involved in the degradation of many peptides including amyloid beta (Aβ), and insulin that play key roles in Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM), respectively. Crystal structure of IDE revealed that N-terminal of IDE has an exosite which serves as a regulation site by orientation of the substrates of IDE to the catalytic site. It is plausible to find small molecules that bind to the exosite of IDE and enhance its proteolytic activity towards different substrates. In this study, we have taken a computer-aided structure based drug design methods combined with experimental methods, one novel molecule that enhances the activity of human IDE was discovered. The novel compound, designated as D10 enhanced both IDE mediated proteolysis of substrate V and insulin degradation. This study describes the first examples of a computer-aided discovery of IDE regulators, showing that in vitro activation of this important enzyme with drug-like small molecules is attainable.
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    Isolation and characterization of cDNAs of lentil ADP-glucose pyrophosphorylase
    (Current Biology Ltd, 2011) Oz, Gul Cevahir; Tulum, Isil; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; Kavaklı, İbrahim Halil; Barış, İbrahim; Faculty Member; Teaching Faculty; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; College of Engineering; College of Sciences; 40319; 111629
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    Transcriptional regulation of the starch branching enzyme isoforms in the leaf and the stemunder long and short photoperiod in lentil
    (Wiley-Blackwell, 2014) Boztas, K.; Morgil, H.; Oz, G. Cevahir; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Barış, İbrahim; Kavaklı, İbrahim Halil; Teaching Faculty; Faculty Member; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; College of Sciences; College of Engineering; 111629; 40319
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    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; 40319
    Light 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.
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    Purification and characterization of a type III photolyase from caulobacter crescentus
    (Amer Chemical Soc, 2008) Öztürk, Nuri; Kao, Ya-Ting; Selby, Christopher P.; Kavakli, I. Halil; Partch, Carrie L.; Zhong, Dongping; Sancar, Aziz; Department of Chemical and Biological Engineering; Kavaklı, İbrahim Halil; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 40319
    The photolyase/cryptochrome family is a large family of flavoproteins that encompasses DNA repair proteins, photolyases, and cryptochromes that regulate blue-light-dependent growth and development in plants, and light-dependent and light-independent circadian clock setting in animals. Phylogenetic analysis has revealed a new class of the family, named type III photolyase, which cosegregates with plant cryptochromes. Here we describe the isolation and characterization of a type III photolyase from Caulobacter crescentus. Spectroscopic analysis shows that the enzyme contains both the methenyl tetrahydrofolate photoantenna and the FAD catalytic cofactor. Biochemical analysis shows that it is a bona fide photolyase that repairs cyclobutane pyrimidine dimers. Mutation of an active site Trp to Arg disrupts FAD binding with no measurable effect on MTHF binding. Using enzyme preparations that contain either both chromophores or only folate, we were able to determine the efficiency and rate of transfer of energy from MTHF to FAD.
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    Discovery of novel CYP17 inhibitors for the treatment of prostate cancer with structure-based drug design
    (Bentham Science Publ Ltd, 2009) N/A; N/A; N/A; Department of Chemical and Biological Engineering; Department of Industrial Engineering; Armutlu, Pelin; Özdemir, Muhittin Emre; Özdaş, Şule Beyhan; Kavaklı, İbrahim Halil; Türkay, Metin; Master Student; Master Student; Researcher; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Department of Industrial Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; N/A; N/A; 40319; 24956
    It has been shown that prostate cancer is associated with elevated androgen biosynthesis; therefore, inhibiting the activity of Cytochrome P450 17 (CYP17) may prevent progression of prostate cancer. In this study we identified, using in silico and experimental methods, two novel steroidal and non-steroidal lead compounds that inhibit the activity CYP17.