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Publication Open Access Cloning, expression, purification, crystallization and X-ray analysis of inositol monophosphatase from Mus musculus and Homo sapiens(Wiley, 2012) Singh, Nisha; Halliday, Amy C.; Knight, Matthew; Lowe, Edward; Churchill, Grant C.; Lack, Nathan Alan; Faculty Member; School of Medicine; 120842Inositol monophosphatase (IMPase) catalyses the hydrolysis of inositol monophosphate to inositol and is crucial in the phosphatidylinositol (PI) signalling pathway. Lithium, which is the drug of choice for bipolar disorder, inhibits IMPase at therapeutically relevant plasma concentrations. Both mouse IMPase 1 (MmIMPase 1) and human IMPase 1 (HsIMPase 1) were cloned into pRSET5a, expressed in Escherichia coli, purified and crystallized using the sitting-drop method. The structures were solved at resolutions of 2.4 and 1.7 angstrom, respectively. Comparison of MmIMPase 1 and HsIMPase 1 revealed a core r.m.s. deviation of 0.516 angstrom.
Publication Metadata only Cornerstones of biochemistry in stamps(Walter De Gruyter Gmbh, 2016) N/A; Ulusu, Nuriye Nuray; Faculty Member; School of Medicine; 6807N/APublication Metadata only COVID-19 may enhance risk of thrombosis and hemolysis in the G6PD deficient patients(Taylor & Francis Inc, 2021) Dağlıoğlu, Gülçin; Candevir, Aslıhan; Kurtaran, Behice; Bozdoğan, Sevcan Tan; İnal, Tamer Cevat; N/A; Aydemir, Duygu; Ulusu, Nuriye Nuray; PhD Student; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; N/A; 6807COVID-19 has become a major public health problem since December, 2019 and no highly effective drug has been found until now. Numbers of infected people and deaths by COVID-19 are increasing every day worldwide, therefore self-isolation and protection are highly recommended to prevent the spread of the virus and especially to protect major risk groups such as the elderly population and people with comorbidities including diabetes, hypertension, cancer, cardiovascular diseases and metabolic syndrome. on the other hand, young people without any secondary disease have died by COVID-19 as well. In this study we compared two male patients infected by COVID-19 at the same age and one of them was diagnosed with G6PD deficiency. Both COVID-19and G6PD deficiency enhance the risk of hemolysis and thrombosis. Serum biochemistry, hemogram and immunological parameters showed that risk of hemolysis and thrombosis may increase in the G6PD deficient patient infected by COVID-19.Publication Open Access Curious cases of the enzymes(De Gruyter Open, 2015) N/A; Ulusu, Nuriye Nuray; Faculty Member; School of Medicine; 6807Life as we know it heavily relies on biological catalysis, in fact, in a very nonromantic version of it, life could be considered as a series of chemical reactions, regulated by the guarding principles of thermodynamics. In ancient times, a beating heart was a good sign of vitality, however, to me, it is actually the presence of active enzymes that counts. Though we do not usually pay attention, the history of enzymology is as old as humanity itself, and dates back to the ancient times. This paper is dedicated to these early moments of this remarkable science that touched our lives in the past and will make life a lot more efficient for humanity in the future. There was almost always a delicate, fundamentally essential relationship between mankind and the enzymes. Challenged by a very alien and hostile Nature full of predators, prehistoric men soon discovered the medicinal properties of the plants, through trial and error. In fact, they accidently discovered the enzyme inhibitors and thus, in crude terms, kindled a sparkling area of research. These plant-derivatives that acted as enzyme inhibitors helped prehistoric men in their pursuit of survival and protection from predators; in hunting and fishing. Later in history, while the underlying purposes of survival and increasing the quality of life stayed intact, the ways and means of enzymology experienced a massive transformation, as the 'trial and error' methodology of the ancients is now replaced with rational scientific theories.Publication Metadata only Does Covid-19 infection alter serum biochemical and hematological biomarkers in deceased dementia patients?(Walter de Gruyter GmbH, 2024) Yucel, Muammer; Koseoglu, Mehmet; Ulusu, Nuriye Nuray; Aydemir, Duygu; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Health SciencesObjectives The elderly population is categorized as a risk group for COVID-19 infection, and dementia is the primary cause of disability in elderly individuals and affects 70 % of the elderly population. In this study, we evaluated the blood and serum biomarkers of deceased dementia patients infected by COVID-19 compared to the survived dementia and non-dementia patients.Methods Laboratory biomarkers of 11 dementia patients infected by COVID-19 have been used for this study. The five patients' serum biochemistry and blood data were compared with the six patients who died because of COVID-19. Additionally, data from nine patients aged 85-96 infected with COVID-19 without dementia have been used to compare the difference between dementia and non-dementia individuals.Results D-dimer, C-reactive protein (CRP), glucose, blood urea nitrogen (BUN), alanine transaminase (ALT), aspartate aminotransferase (AST), troponin, procalcitonin, red cell distribution width (RDW), white blood cell (WBC), neutrophil (NEU) and %NEU levels significantly increased in the deceased dementia patients compared to the survived and non-dementia individuals. Calcium (Ca), hematocrit (HCT), red blood cells (RBC), lymphocyte (%LYM), monocyte %MONO, and basophil (%BASO) levels significantly decreased in the deceased dementia patients compared to the survived and non-dementia individuals infected by COVID-19.Conclusions Serum biochemistry and hematological biomarkers, including D-dimer, CRP, glucose, ALT, AST, BUN, troponin, procalcitonin, RDW, RBC, WBC, NEU, %NEU, Ca, HCT, %LYM, %MONO, and %BASO were significantly altered in deceased dementia patients infected by COVID-19 compared to the survived individuals.Publication Open Access Effects of timolol treatment on pancreatic antioxidant enzymes in streptozotocin-induced diabetic rats: an experimental and computational study(Sciendo, 2019) Gök, Müslüm; Turan, Belma; N/A; Department of Chemical and Biological Engineering; Ulusu, Nuriye Nuray; Erman, Burak; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; School of Medicine; College of Engineering; 6807; 179997Background: the study aimed to investigate whether timolol-treatment has a beneficial effect on pentose phosphate pathway enzyme activities such as glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGDH) enzyme activities and cAMP level in streptozotocin-induced diabetic rats in pancreatic tissues. Methods: diabetes was induced by streptozotocin (STZ) in 3-month old male Wistar rats. The diabetic rats were treated with timolol (5 mg/kg body weight, for 12 weeks) while the control group received saline. Enzyme activities were determined in pancreas tissue. To support our results, we performed in silico calculations, using Protein Data Bank structures. Results: timolol treatment of STZ-induced diabetic rats had no noteworthy effect on high blood-glucose levels. However, this treatment induced activities of G6PD and 6PGDH in diabetic rats. Timolol treatment significantly increased cAMP level in diabetic pancreatic tissue. We found that timolol cannot bind strongly to either G6PD or 6PGD, but there is a relatively higher binding affinity to adenylyl cyclase, responsible for cAMP production, serving as a regulatory signal via specific cAMP-binding proteins. Conclusions: our data point out that timolol treatment has beneficial effects on the antioxidant defence mechanism enzymes in the pancreas of STZ-induced diabetic rats. / Uvod: cilj istrazivanja je bio da se utvrdi da li tretman timololom ima pozitivan efekat na aktivnosti enzima pentoze fosfata, kao sto su aktivnosti glukoze-6-fosfat dehidrogenaze (G6PD), enzimske aktivnosti 6-fosfoglukonat dehidrogenaze i cAMP nivo u tkivu pankreasa kod pacova kojima je dijabetes izazvan streptozotocionom. Metode: dijabetes je izazvan streptozotocionom (STZ) kod tromesecnih muzjaka vistar pacova. Pacovi sa dijabetesom su tretirani timololom (5 mg/kg telesne tezine tokom 12 nedelja), dok je kontrolna grupa primila fizioloski rastvor. Enzimske aktivnosti su utvrivane u tkivu pankreasa. Da bismo potkrepili nase rezultate, sproveli smo in silico racunanja koristeci strukture Proteinske baze podataka. Rezultati: tretman timololom na pacovima kojima je dijabetes izazvan putem STZ-a nije imao znacajan uticaj na visoke nivoe glukoze u krvi. Medutim, kod takvih pacova ovaj tretman je indukovao aktivnosti G6PD i 6PGDH. Lecenje timololom znacajno je povecalo nivo cAMP-a u dijabeticnom tkivu pankreasa. Utvrdili smo da se timolol ne moze snazno vezati ni za G6PD, ni za 6PGD, ali da postoji relativno veci afinitet vezivanja za adenilil ciklazu, odgovornu za proizvodnju cAMP, koja sluzi kao regulatorni signal putem odredenih cAMP vezivnih proteina. Zakljucak: nasi podaci ukazuju da tretman timololom ima pozitivne efekte na antioksidantne enzime od brambenog sistema u pankreasu pacova sa dijebetesom izazvanim putem STZ-a.Publication Open Access Evaluation of renal function in Alzheimer's disease and geriatric patients: Results from a turkish two-center study(De Gruyter, 2017) Erbayraktar, Zübeyde; Evlice, Ahmet Turan; Yılmaz, Gökhan; Yazıcı, Canan; Yener, Görsev; N/A; Ulusu, Nuriye Nuray; Faculty Member; School of Medicine; 6807Background: Alzheimer's disease (AD) is a severe multifactorial neurodegenerative proteopathy associated with advanced age. Discrepancies in the renal function of these patients compared to geriatric patients with dementia have rarely been reported. In this study, we aimed to disclose the importance of associated renal changes for the patho genesis of AD. Methods: Patients with AD (n = 107) and geriatric patients with dementia and without dementia (n = 124) (231 patients in total) from Dokuz Eylul and Cukurova University Hospitals were enrolled in the study. We measured serum Na, K, Cl, Ca, BUN, creatinine, total protein levels and MDRD [eGFR] in all groups. Results: From Izmir Center, the first study arm consisted of patients with AD dementia (n = 74), and the second arm included geriatric patients with dementia (n = 79). From Adana, 78 patients were recruited to the study, of which 33 were with AD and 45 were geriatric patients without dementia. When we analyzed comparatively the AD and geriatric dementia patients study arms, a statistically significant difference was observed both in the median age (p < 0.001), as well as in the biochemical parameters from Izmir Center: Na (p < 0.001), K (p < 0.001), Cl (p < 0.05), Ca (p < 0.001), BUN (p < 0.05), creatinine (p < 0.001), total protein (p < 0.001) and MDRD [eGFR] (p < 0.001). How ever, these were not significantly different between AD and geriatric patients without dementia in the Adana group. Conclusions: Our results indicate that renal function is prone to alterations in different age groups of patients with AD. However, there is no conclusive evidence that renal function is one of the risk factors in AD.Publication Metadata only Investigation of the role of quercetin as a heat shock protein inhibitor on apoptosis in human breast cancer cells(Springer, 2020) Kiyga, Ezgi; Sengelen, Aslihan; Onay Ucar, Evren; N/A; Adıgüzel, Zelal; Faculty Member; School of Medicine; 251865High expression of heat shock proteins (HSP) in breast cancer has been closely associated with tumor cell proliferation and thus a poor clinical outcome. Quercetin, a good Hsp inhibitor as a dietary flavonoid, possesses anticarcinogenic properties. Although there are many studies on the effects of quercetin on Hsp levels in human breast cancer cells, research on elucidation of its molecular mechanism continues. Herein, we aimed to investigate the effect of quercetin on Hsp levels and whether quercetin is a suitable therapeutic for two breast cancer cell lines (MCF-7 and MDA-MB-231) representing breast tumors which differed in hormone receptor, aggressiveness and treatment responses. To examine the response to high and low doses of quercetin, the cells were treated with three doses of quercetin (10, 25 and 100 mu M) determined by MTT. The effects of quercetin on Hsp levels, apoptosis and DNA damage were examined by western blot analysis, caspase activity assay, comet assay and microscopy in human breast cancer cells. Compared to MDA-MB231 cells, MCF-7 cells were more affected by quercetin treatments. Quercetin effectively suppressed the expression of Hsp27, Hsp70 and Hsp90. While quercetin did not induce DNA damage, it triggered apoptosis at high levels. Although an increase in NF-kappa B levels is observed in the cells exposed to quercetin, the net result is the anticancer effect in case of Hsp depletion and apoptosis induction. Taken together our findings suggested that quercetin can be an effective therapeutic agent for breast cancer therapy regardless of the presence or absence of hormone receptors.Publication Open Access PRISM-EM: template interface-based modelling of multi-protein complexes guided by cryo-electron microscopy density maps(International Union of Crystallography, 2016) Nussinov, Ruth; Department of Chemical and Biological Engineering; Kuzu, Güray; Keskin, Özlem; Gürsoy, Attila; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; Graduate School of Sciences and Engineering; N/A; 26605; 8745The structures of protein assemblies are important for elucidating cellular processes at the molecular level. Three-dimensional electron microscopy (3DEM) is a powerful method to identify the structures of assemblies, especially those that are challenging to study by crystallography. Here, a new approach, PRISM-EM, is reported to computationally generate plausible structural models using a procedure that combines crystallographic structures and density maps obtained from 3DEM. The predictions are validated against seven available structurally different crystallographic complexes. The models display mean deviations in the backbone of <5 angstrom. PRISM-EM was further tested on different benchmark sets; the accuracy was evaluated with respect to the structure of the complex, and the correlation with EM density maps and interface predictions were evaluated and compared with those obtained using other methods. PRISM-EM was then used to predict the structure of the ternary complex of the HIV-1 envelope glycoprotein trimer, the ligand CD4 and the neutralizing protein m36.