Publications by authors named "Tolga Aslan"

2 Publications

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Identifying and elucidating the roles of Y198N and Y204F mutations in the PAH enzyme through molecular dynamic simulations.

J Biomol Struct Dyn 2021 May 10:1-12. Epub 2021 May 10.

Faculty of Arts and Sciences, Department of Molecular Biology and Genetics, Bogazici University, Istanbul, Turkey.

Phenylketonuria is an autosomal recessive disorder caused by mutations in the phenylalanine hydroxylase gene. In phenylketonuria causes various symptoms including severe mental retardation. PAH gene of a classical Phenylketonuria patient was sequenced, and two novel heterozygous mutations, p.Y198N and p.Y204F, were found. This study aimed to reveal the impacts of these variants on the structural stability of the PAH enzyme. analyses using prediction tools and molecular dynamics simulations were performed. Mutations were introduced to the wild type catalytic monomer and full length tetramer crystal structures. Variant pathogenicity analyses predicted p.Y198N to be damaging, and p.Y204F to be benign by some prediction tools and damaging by others. Simulations suggested p.Y198N mutation cause significant fluctuations in the spatial organization of two catalytic residues in the temperature accelerated MD simulations with the monomer and increased root-mean-square deviations in the tetramer structure. p.Y204F causes noticeable changes in the spatial positioning of T278 suggesting a possible segregation from the catalytic site in temperature accelerated MD simulations with the monomer. This mutation also leads to increased root-mean-square fluctuations in the regulatory domain which may lead to conformational change resulting in inhibition of dimerization and enzyme activation. Our study reports two novel mutations in the PAH gene and gives insight to their effects on the PAH activity. MD simulations did not yield conclusive results that explains the phenotype but gave plausible insight to possible effects which should be investigated further with and studies to assess the roles of these mutations in etiology of PKU. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1921619DOI Listing
May 2021

Analysis of the Wnt/B-catenin/TCF4 pathway using SAGE, genome-wide microarray and promoter analysis: Identification of BRI3 and HSF2 as novel targets.

Cell Signal 2010 Oct 9;22(10):1523-35. Epub 2010 Jun 9.

Department of Molecular Biology and Genetics, Bogazici University, Istanbul, Turkey.

The Wnt signaling pathway is involved in many differentiation events during embryonic development and can lead to tumor formation after aberrant activation of its components. beta-catenin, a cytoplasmic component, plays a major role in the transduction of canonical Wnt signaling. The aim of this study was to identify novel genes that are regulated by active beta-catenin/TCF signaling in hepatocellular carcinoma-derived Huh7 cells with high (transfected) and low beta-catenin/TCF activities. High TCF activity Huh7 cells led to earlier and larger tumor formation when xenografted into nude mice. SAGE (Serial Analysis of Gene Expression), genome-wide microarray and in silico promoter analysis were performed in parallel, to compare gene expression between low and high beta-catenin/TCF activity clones, and also those that had been rescued from the xenograft tumors. SAGE and genome-wide microarray data were compared and contrasted. BRI3 and HSF2 were identified as novel targets of Wnt/beta-catenin signaling after combined analysis and confirming experiments including qRT-PCR, ChIP, luciferase assay and lithium treatment.
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http://dx.doi.org/10.1016/j.cellsig.2010.05.021DOI Listing
October 2010