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Öğe Effects of Salicylic Acid on Fatty Acid Gene Expression in Carthamus tinctorious L. cv. Dinçer under Pendimethalin Stress(Munzur Üniversitesi, 2020) Akbulut, EkremPendimethalin is a member of the dinitroaniline class herbicide. It used to control most annual grasses and many annual broad-leaved weeds. Salicylic acid acts as an endogenous signal molecule in charge of inducing environmental stress tolerance in plants. Omega-3 fatty acid desaturase is a key enzyme for ?-linolenic acid biosynthesis. Here, we searched to understand the beneficial impacts of salicylic acid on fatty acid desaturase gene (FAD3 and FAD7) expression during pendimethalin stress in safflower (Carthamus tinctorious cv. “Dinçer). In this study, 0.004 and 0.01 M pendimethalin was applied to safflower plants grown under controlled climatic conditions in 36 pots. 0.05 mM salicylic acid was applied to the samples where pendimethalin was applied. After application, gene expression analyze were performed using quantitative polymerase chain reaction. The floor change between the test and control groups was calculated with the formula 2 ^ (delta delta CT). The change between gene expression levels was evaluated by t test (p <0.05). FAD3 and FAD7 expression levels decreased at low pendimethalin concentration. A down-regulation in FAD3 expression was observed in high pendimethalin stress, while an up-regulation in FAD7 expression was detected. Salicylic acid had a ameliorative effect on the negative effect of pendimethalin stress on FAD3 and FAD7 gene expression.Öğe The Effects of SARS CoV-2 nsp13 Mutations on the Structure and Stability of Helicase in Chinese Isolates(İstanbul Üniversitesi / İstanbul University, 2022) Akbulut, EkremObjective: Coronavirus Disease 2019 (COVID19) is a viral disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2). The high mutation propensity of the SARS CoV-2 genome is one of the biggest threats to the long-term validity of treatment options. Helicases are anti-viral targets because of the vital role they play in the viral life cycle. In this study, changes in the protein structure caused by SARS CoV-2 nsp13 mutations were investigated to contribute to the development of effective antiviral drugs. Materials and Methods: Genome data of 298 individuals located in the China location were examined. The mutant model was built using deep learning algorithms. Model quality assessment was done with QMEAN. Protein stability analyses were performed with DynaMut2 and Cutoff Scanning Matrix stability. Changes in substrate affinity were performed with Haddock v2.4. Results: In this study, twenty-eight mutations in nsp13 were identified (23 sense, 5 missense). The changes in protein structure caused by the five missense mutations (Leu14Phe, Arg15Ser, Arg21Ser, Leu235Phe, Ala454Thr) were modeled. The mutations caused a decrease in the stability of SARS CoV-2 helicase (-0.99, -1.66, -1.15, -0.54, and -0.73 for Leu14Phe, Arg15Ser, Arg21Ser, Leu235Phe, Ala454Thr, respectively). The mutations reduced the helicase's affinity to the substrate. The docking scores for wild-type and mutant helicase were -84.4±1.4 kcal.mol-1 and -71.1±6.7 kcal.mol-1, respectively. Conclusion: Helicase mutations caused a decrease in the protein stability and nucleic acid affinity of the SARS CoV-2 helicase. The results provide important data on the development of potential antivirals and the effect of mutation on the functions of viral proteins.Öğe Endoplasmic reticulum aminopeptidase-1 polymorphism increases the risk of rheumatoid arthritis(2022) Akbulut, Ekrem; Yıldırım, Tülay; Öztürk, OnurObjectives: Endoplasmic reticulum aminopeptidase-1 (ERAP1) polymorphic changes cause autoimmunity. To understand the contribution of ERAP1 to the occurrence of rheumatoid arthritis (RA) disease, we investigated the relationship between ERAP1 and RA. Methods: This study was conducted with 201 patients and 171 healthy controls. The rs26653, rs27044, rs27582, rs28096, and rs30187 polymorphic regions of ERAP1 were investigated. The comparison was done with Arlequin software and logistic regression. Haplotypes were analyzed with Phylogenetic Network software. ERAP1 was modeled using Promod3. Topological changes in ERAP1were analyzed with TM-Score. Results: The results showed that rs26653G>C (p=0.002, OR=2.001, 95%CI=1.276–3.137), rs27044C>G (p=0.037, OR=1.583, 95%CI=1.028–2.440), rs27582G>A (p<0.05, OR=0.348, 95%CI=0.194–0.622) and rs30187C>T (p=0.006, OR=1.849, 95%CI=1.191–2.870) polymorphisms are associated with RA disease risk. The relationship between rs28096 polymorphism and RA disease risk could not be determined (p=0.509). The risk haplotype for rheumatoid arthritis was determined as [CGAAT]. It was determined that polymorphisms of ERAP1 cause changes in the entry pocket of substrate and ligand. Conclusions: We report a haplotype [CGAAT] that is associated with RA risk from Turkey that has not been described before. These data will make important contributions to elucidating the molecular mechanism of RA.Öğe Investigation of changes in protein stability and substrate affinity of 3CL-protease of SARS-CoV-2 caused by mutations(Sociedade Brasileira de Genetica, 2022) Akbulut, Ekrem3CLpro of SARS-CoV-2 is one of the enzymes required for the replication process of the virus responsible for the COVID-19 pandemic. In this study, changes in protein stability and substrate affinity caused by mutations were investigated to stir the development of potent inhibitors. Sequence data of samples were obtained from the NCBI Virus database. Mutation analyses were performed with RDP4 and MegaX. 3CLpro tertiary models were created using Robetta. Molecular docking for peptidomimetic substrate and inhibitor ligand was done with Autodock v4.2 and Haddock v2.4. Protein stability analysis was performed using mCSM stability and DynaMut2. Twenty-four missense mutations in 3CLpro were identified in this study. Changes in the 3CLpro structure induced by the mutations Met49Thr, Leu167Ser, and Val202Ala resulted in significant levels of instability (-2.029,-2.612,-2.177 kcal.mol-1, respectively). The lowest interaction energy for substrate was-58.7 kcal.mol-1 and-62.6 kcal.mol-1 in wild-type and mutant, respectively. The lowest docking energy for ligand was-6.19 and-9.52 kcal.mol-1 for wild-type and mutant, respectively. This study reports for the first time that mutations cause increased substrate affinity of 3CLpro from SARS-CoV-2. This research provides important data for the development of potent peptidomimetic inhibitors for the treatment of COVID-19.Öğe Mutations in the SARS CoV-2 spike protein may cause functional changes in the protein quaternary structure(Turkish Journal of Biochemistry, 2021) Akbulut, EkremObjectives: This study aimed to model the changes resulting from mutations in surface (spike/S) glycoproteins, which play a key role in the entry of the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) into host cells, in a protein quaternary structure and to evaluate their possible effects on the functional structure. Methods: Genome sequence information of SARS CoV-2-infected patients located in Turkey was obtained from the GISAID EpiCoV database. Structural analysis of spike proteins was done using bioinformatics tools (MAFFT, PSIPRED, ProMod3, PyMoL and DynOmics). Results: We identified 76 Thr>Ile mutations in the N-terminal domain; 468 Ile>Val mutations in the receptor binding site and 614 Asp>Gly, 679 Asn>Lys, 771 Ala>Val and 772 Val>Ile mutations in the S1 subunit. It has been observed that the mutations, except those of residues 771 and 772, may cause significant conformational, topological and electrostatic changes in a protein quaternary structure. It has been determined that the mutations in the receptor binding site transform the protein structure into a formation that can mask the binding site and affect receptor affinity. Conclusions: It has been considered that SARS CoV-2 S glycoprotein mutations may cause changes in a protein functional structure that can affect the severity of disease.Öğe Pendimethalin ve Salisilik Asit Uygulamalarının Carthamus tinctorius L. cv. “Remzibey” Yağ Asidi Desatüraz Genlerinin Anlatımı Üzerine Etkisi(Iğdır Üniversitesi, 2020) Akbulut, EkremAspir (Carthamus tinctorius L.), tohumlarında yüksek kaliteye sahip doymamış yağ asitlerinden oleikasit ve ?-linolenik asit içeren endüstriyel hammadde kaynağı olma özelliğine sahip önemli bir yağ bitkisidir.Pendimethalin yabancı ot kontrolünün sağlanması için ekonomik değere sahip bitkilere uygulanan dinitroanilingrubu bir herbisittir. Salisilik asit biyotik ve abiyotik streslere karşı bitki savunmasında yer alan önemli bir bitkiselhormondur. Omega-3 yağ asidi desatürazlar (FAD3 ve FAD7) ?-linolenik asit biyosentezi için anahtarenzimlerdir. Bu çalışmada pendimethalin ve salisilik asitin yağ asidi metabolizmasında görev alan FAD3 ve FAD7gen anlatım düzeyleri üzerindeki olası etkileri araştırılmıştır. Çalışmada toplam 36 saksıda kontrollü iklimşartlarında yetiştirilen aspir bitkilerine 0,004 ve 0,01 M pendimethalin uygulaması yapılmıştır. Pendimethalinuygulanan örneklere 0,05 mM salisilik asit uygulanmıştır. Uygulama sonrası RNA izolasyonu, cDNA sentezi vekantitatif polimeraz zincir reaksiyonu gerçekleştirilmiştir. Test ve kontrol grupları arasındaki kat değişimi 2^ (-delta delta CT) formülü ile hesaplanmıştır. Gen anlatım düzeyleri arasındaki değişim t testi ile değerlendirildi(p<0,05). Pendimethalinin FAD3 ve FAD7 genlerini aşağı yönde regüle ettiği, artan pendimethalinkonsantrasyonuna bağlı olarak gen anlatım düzeylerinin azaldığı belirlenmiştir. Salisilik asitin pendimethalininortaya çıkardığı toksik etkiyi azaltıcı yönde etki gösterdiği, FAD3 ve FAD7 genlerini yukarı yönlü regüle ettiğitespit edilmiştir. Pendimethalinin Carthamus tinctorius L. Remzibey çeşidinde yağ asidi kalitesi ve ?-linolenikasit biyosentezinde azalmaya neden olabileceği, salisilik asitin ise pendimethalinin olumsuz etkilerini gidericietkiye sahip olduğu ve ?-linolenik asit miktarında kısmi artışa katkı sunabileceği düşünülmektedir.Öğe The role of A268V exon-7 polymorphism of PPARA in development of axial spondyloarthritis(WALTER DE GRUYTER GMBHGENTHINER STRASSE 13, D-10785 BERLIN, GERMANY, 2021) Akbulut, Ekrem; Yolbas, S; Ozgen, MObjectives: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that mainly affects the axial skeleton. Peroxisome proliferator activated receptor alpha (PPARA) is an intracellular transcription factor, which play a role in inflammation and osteoblasting activity. This study is designed to investigate the relationship of NG_012204.2:p.A1a268Val polymorphism of PPARA with axSpA risk and its role in disease development. Methods: This study was conducted with 168 patients and 181 controls. Genotyping was done with MALDITOF. Gene expression level was analyzed by quantitative real time PCR (RT-qPCR). The protein homology models of PPARA were created with ProMod3. Ligand binding dynamics were tested using the AutoDock4 docking program. Statistical evaluations were made with SPSS (ver24) and GeneGlobe. Results: Our results showed that C>T polymorphism causing NG_012204.2:p.A1a268Val change was associated with disease risk (p=0.024) and T allele increased disease risk 1.7 times (95% CI=1.070-2.594). PPARA expression decreased (p<0.05) in individuals carrying the T allele. We determined that the ligand entry pocket was opened 1.1 A in the polymorphic PPARA. Polymorphic change caused a decrease in the ligand binding affinity. Conclusions: Our results provide an important contribution to elucidating the development of axSpA and demonstrate the potential of PPARA as a marker for the diagnosis of axSpA.Öğe SARS CoV-2 nsp1 Mutasyonlarının Protein Yapıda Ortaya Çıkardığı Değişimler(Munzur Üniversitesi, 2020) Akbulut, EkremŞiddetli akut solunum yolu sendromu koronavirüsü 2 (SARS CoV-2) pozitif polariteli ve tek iplikli bir RNA virüsüdür. Virüsün sebep olduğu COVID19 hastalığı on ay gibi kısa bir sürede 900 binden fazla insanın ölümüne neden oldu. Virüs ile mücadelede etkin ve spesifik bir ilaç ve aşı henüz bulunmamaktadır. İlaç ve aşı geliştirme çalışmaları virüsün yapısal ve fonksiyonel özelliklerinin kapsamlı bir şekilde anlaşılmasını gerekli kılmaktadır. Hızlı yayılım gösteren virüsün yüksek mutasyon hızı geliştirilecek aşı ve ilaçların etkinliklerini sürdürebilmelerinin önündeki en büyük engellerden biridir. Hücresel boyutta viral enfeksiyonun başlangıcında yer alan SARS CoV-2 yapısal olmayan protein 1 (nsp1) önleyici tedavi için potansiyel hedef proteindir. Konak hücre translasyonunu engelleyen nsp1’in yapısının bilinmesi önemlidir. Bu çalışmada 222 Avrupa izolatında görülen nsp1 mutasyonlarının protein yapıda ortaya çıkarabileceği değişimler yapay zekâ tabanlı bir modelleme yazılımı olan trRosetta kullanılarak modellenmiştir. NCBI Virüs veritabanından elde edilen dizi bilgileri MAFFT çoklu dizi hizalama programı ile hizalanmıştır. Mutasyon analizleri RDP4 yazılımı ile yapılmıştır. Mutant protein primer yapı MegaX yazılımı ile oluşturulmuştur. Protein kalite skorları QMEAN algoritması kullanılarak analiz edilmiştir. Proteinleri fizikokimyasla özellikleri ProtParam ExPAsy programı ile yapılmıştır. Elde edilen protein yapıların konformasyonel analizleri PyMOL ile yapılmıştır. SARS CoV-2 Avrupa izolatlarında görülen nsp1 mutasyonlarının protein sekonder ve tersiyer yapısında konformasyonel ve topolojik değişimlere neden olabileceği tespit edilmiştir. SARS CoV-2 katalitik bölgeyi içine alan P153 ve N178 rezidüleri arasında kalan bölgede görülen değişimin proteinin fonksiyonel özelliklerini etkileyebileceği düşünülmektedir. Elde edilen verilerin önleyici ve tedavi edici yaklaşımlara önemli veriler sunabileceği düşünülmektedir.Öğe SARS CoV-2 Spike glycoprotein mutations and changes in protein structure(Trakya Üniversitesi, 2021) Akbulut, EkremSevere Acute Respiratory Syndrome Corona Virus-2 (SARS CoV-2) is a single-stranded positive polarity RNA virus with a high virulence effect. Spike (S) glycoprotein is the outermost component of the SARS CoV-2 virion and is important in the entry of the virus into the cell via the angiotensin converting enzyme 2 (ACE2) receptor. ACE2 plays an important role in the regulation of human blood pressure by converting the vasoconstrictor angiotensin 2 to the vasodilator angiotensin 1-7. In this study, the changes that mutations in Asian isolates may cause in S glycoprotein structure were analyzed and modeled to contribute to drug and vaccine targeting studies. Genome, proteome and mutation analyses were done using bioinformatics tools (MAFFT, MegaX, PSIPRED, MolProbity, PyMoL). Protein modelling was performed using ProMod3. We detected 26 mutations in the S glycoprotein. The changes that these mutations reveal in the general topological and conformational structure of the S glycoprotein may affect the virulence features of SARS CoV-2. It was determined that mutations converted the receptor binding domain (RBD) from down-formation to like-up formation. It is thought that conformational change occurring after mutation in RBD may cause an increase in receptor affinity. These findings could be beneficial for disease prevention of and drug/vaccine development for SARS CoV-2.
