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FEBS Journal

Mariana A Ajalla Aleixo, Victor L Rangel, Joane K Rustiguel, Ricardo A P de Pádua, M Cristina Nonato
Fumarate hydratases (FHs, fumarases) catalyze the reversible conversion of fumarate into L-malate. FHs are distributed over all organisms and play important roles in energy production, DNA repair and as tumor suppressors. They are very important targets both in the study of human metabolic disorders and as potential therapeutic targets in neglected tropical diseases and tuberculosis. In this study, human FH (HsFH) was characterized by using enzyme kinetics, differential scanning fluorimetry (DSF) and X-ray crystallography...
February 14, 2019: FEBS Journal
Kengo Kitadokoro, Kakara Mizuki, Shingo Matsui, Ryouhei Osokoshi, Thumarat Uschara, Fusako Kawai, Shigeki Kamitani
Cutinases are enzymes known to degrade polyester-type plastics. Est119, a plastic-degrading type of cutinase from Thermobifida alba AHK119 (herein called Ta_cut), shows a broad substrate specificity toward polyesters, and can degrade substrates including polylactic acid (PLA). However, the PLA-degrading mechanism of cutinases is still poorly understood. Here, we report the structure complexes of cutinase with ethyl lactate (EL), the constitutional unit. From this complex structure, the electron density maps clearly showed one lactate (LAC) and one EL occupying different positions in the active site cleft...
February 14, 2019: FEBS Journal
Dezhi Zheng, Yong Zhang, Yonghe Hu, Jing Guan, Lianbin Xu, Wenjing Xiao, Qinyue Zhong, Chao Ren, Jinfeng Lu, Jiali Liang, Jun Hou
Diabetic cardiomyopathy (DCM) - ventricular dysfunction in the absence of underlying heart disease - is a common complication of diabetes and a leading cause of mortality associated with the disease. In DCM, cardiac fibrosis is the main cause of heart failure (HF). Although it is well-established that the transforming growth factor-beta (TGF-β) signaling pathway plays a part in inducing cardiac fibrosis in DCM, details of the molecular mechanism involved remain elusive. Therefore, it is crucial to study the gene regulation of key signaling effectors in DCM-associated cardiac fibrosis...
February 12, 2019: FEBS Journal
Raquel L Bernardino, Tânia R Dias, Bruno P Moreira, Mariana Cunha, Alberto Barros, Elsa Oliveira, Mário Sousa, Marco G Alves, Pedro F Oliveira
The process that allows cells to control their pH and bicarbonate levels is essential for ionic and metabolic equilibrium. Carbonic anhydrases (CAs) catalyse the conversion of CO2 to HCO3 - and H+ and are thus essential for this process. Herein, we inhibited CAs with acetazolamide - ACT and SLC-0111 - to study their involvement in the metabolism, mitochondrial potential, mitochondrial biogenesis and lipid metabolism of human Sertoli cells (hSCs), obtained from biopsies from men with conserved spermatogenesis...
February 6, 2019: FEBS Journal
Guosen Wang, Weiwei Sheng, Xiaoyang Shi, Xin Li, Jianping Zhou, Ming Dong
Serine/arginine protein specific kinase 2 (SRPK2) plays a vital role in the progression of a range of different malignancies, including pancreatic cancer. However, the mechanisms are poorly understood. Previous studies have shown that in hepatocellular carcinoma, SRPK2 knockdown leads to upregulation of the cell fate determining protein Numb, and in pancreatic cancer cells, Numb knockdown prevents ubiquitin-mediated degradation of p53. In this study, we investigated the relationship between SRPK2, Numb and p53 in the development of pancreatic cancer with or without chemical agent treatment in vitro...
February 6, 2019: FEBS Journal
Anastasia G Tavianatou, Ilaria Caon, Marco Franchi, Zoi Piperigkou, Devis Galesso, Nikos K Karamanos
Hyaluronan (HA) is a linear non-sulfated glycosaminoglycan of the extracellular matrix that plays a pivotal role in a variety of biological processes. High molecular size HA exhibit different biological properties than oligomers and low molecular size HA. Depending on their molecular size, HA fragments can influence cellular behavior in a different mode of action. This phenomenon is attributed to the different manner of interaction with the HA receptors, especially CD44 and RHAMM. Both receptors can trigger signaling cascades that regulate cell functional properties, such as proliferation and migration, angiogenesis and wound healing...
February 6, 2019: FEBS Journal
Sang-Min Park, Chae Young Hwang, Sung-Hwan Cho, Daewon Lee, Jeong-Ryeol Gong, Soobeom Lee, Sohee Nam, Kwang-Hyun Cho
Cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGFR), is being widely used for colorectal cancer (CRC) with wild-type KRAS. However, its responsiveness is still very limited and wild-type KRAS is not enough to indicate such responsiveness. Here, by analyzing the gene expression data of CRC patients treated with cetuximab monotherapy, we have identified DUSP4, ETV5, GNB5, NT5E, and PHLDA1 as potential targets to overcome cetuximab resistance. We found that knockdown of any of these 5 genes can increase cetuximab sensitivity in KRAS wild-type cells...
February 4, 2019: FEBS Journal
Donald E Spratt, Kathryn R Barber, Nicole M Marlatt, Vy Ngo, Jillian A Macklin, Yiming Xiao, Lars Konermann, Martin L Duennwald, Gary S Shaw
The assembly of proteins into dimers and oligomers is a necessary step for the proper function of transcription factors, muscle proteins and proteases. In uncontrolled states, oligomerization can also contribute to illnesses such as Alzheimer's disease. The S100 protein family are a group of dimeric proteins that have important roles in enzyme regulation, cell membrane repair and cell growth. Most S100 proteins have been examined in their homodimeric state, yet some of these important proteins are found in similar tissues implying that heterodimeric molecules can also be formed from the combination of two different S100 members...
February 4, 2019: FEBS Journal
Ahmad Abdullah, Priti Talwar, Christian Lefebvre d'Hellencourt, Palaniyandi Ravanan
Neuroblastoma is an embryonic malignancy that arises out of the neural crest cells of the sympathetic nervous system. It is the most common childhood tumor known for its spontaneous regression via the process of differentiation. The induction of differentiation using small molecules such as retinoic acid is one of the therapeutic strategies to treat the residual disease. In this study, we have reported the effect of kaempferol in inducing differentiation of neuroblastoma cells in vitro. Treatment of neuroblastoma cells with kaempferol reduced the proliferation and enhanced apoptosis along with the induction of neuritogenesis...
February 4, 2019: FEBS Journal
Lukasz Skalniak, Aleksandra Twarda-Clapa, Constantinos G Neochoritis, Ewa Surmiak, Monika Machula, Aneta Wisniewska, Beata Labuzek, Ameena M Ali, Sylwia Krzanik, Grzegorz Dubin, Matthew Groves, Alexander Dömling, Tad A Holak
The p53 protein is engaged in the repair of DNA mutations and elimination of heavily damaged cells, providing anti-cancer protection. Dysregulation of p53 activity is a crucial step in carcinogenesis. This dysregulation is often caused by the overexpression of negative regulators of p53, among which MDM2 is the most prominent one. Antagonizing MDM2 with small molecules restores the activity of p53 in p53 wild-type (p53wt ) cells and thus provides positive outcomes in the treatment of p53wt cancers. Previously, we have reported the discovery of a panel of fluoro-substituted indole-based antagonists of MDM2...
February 4, 2019: FEBS Journal
Ming-Shih Hwang, Jérôme Boulanger, Jonathan D Howe, Anna Albecka, Mathias Pasche, Leila Mureşan, Yorgo Modis
Double-stranded RNA (dsRNA) is a potent proinflammatory signature of viral infection and is sensed primarily by RIG-I-like receptors (RLRs). Oligomerization of RLRs following binding to cytosolic dsRNA activates and nucleates self-assembly of the mitochondrial antiviral signaling protein (MAVS). In the current signaling model, the caspase recruitment domains of MAVS form helical fibrils that self-propagate like prions to promote signaling complex assembly. However, there is no conclusive evidence that MAVS forms fibrils in cells or with the transmembrane anchor present...
February 4, 2019: FEBS Journal
Luca Mureddu, Geerten W Vuister
Nuclear Magnetic Resonance (NMR) is one of the major techniques for investigating the structure, dynamics and interactions between biomolecules. However, non-experts often experience NMR experimentation and data analysis as intimidating. We discuss a simple yet powerful NMR technique, the so-called chemical shift perturbation (CSP) analysis, as a tool to elucidate macromolecular interactions in small- and medium-sized complexes, including protein-protein, protein-drug, and protein-DNA/RNA interactions. We discuss current software packages for NMR data analysis and present a new interactive graphical tool implemented in CcpNmr AnalysisAssign version-3, which can drastically reduce the time required for the CSP analysis...
February 1, 2019: FEBS Journal
Hongju Ma, Daniel Holub, Natacha Gillet, Gero Kaeser, Katharina Thoulass, Marcus Elstner, Norbert Krauß, Tilman Lamparter
Prokaryotic (6-4) photolyases branch at the base of the evolution of cryptochromes and photolyases. Prototypical members contain an iron-sulphur cluster which was lost in the evolution of the other groups. In the Agrobacterium (6-4) photolyase PhrB, the repair of DNA lesions containing UV-induced (6-4) pyrimidine dimers is stimulated by Mg2+ . We propose that Mg2+ is required for efficient lesion-binding and for charge stabilization after electron transfer from the FADH- chromophore to the DNA lesion. Furthermore, two highly conserved Asp residues close to the DNA binding site are essential for the effect of Mg2+ ...
January 31, 2019: FEBS Journal
Ana Raquel Ramos, Somadri Ghosh, Matthias Dedobbeleer, Pierre A Robe, Bernard Rogister, Christophe Erneux
Cell migration is an important process that occurs during development and has also been linked to the motility of cancer cells. Cytoskeleton reorganization takes place in the migration process leading to lamellipodia formation. Understanding the molecular underpinnings of cell migration is particularly important in studies of glioblastoma, a highly invasive and aggressive cancer type. Two members of the phosphoinositide 5-phosphatase family, SKIP and SHIP2, have been associated with cell migration in glioblastoma; however, the precise role these enzymes play in the process - and whether they work in concert - remains unclear...
January 29, 2019: FEBS Journal
Jie Lu, Mingshu Sun, Xinjiang Wu, Xuan Yuan, Zhen Liu, Xiaojie Qu, Xiaopeng Ji, Tony R Merriman, Changgui Li
Hyperuricemia (HU) is a cause of gout. Clinical studies show a link between HU and cardiovascular disease. However, the role of soluble serum urate (SU) on atherosclerosis development remains elusive. We aimed to use a new HU mouse model [Uricase/Uox knockout (KO)] to further investigate the relationship between HU and atherosclerosis. A mouse model by perivascular collar placement of induced carotid atherosclerosis was established in male Uox-KO mice. The Uox-KO mice had elevated SU levels and enhanced levels of atherosclerosis inflammatory response proteins...
January 28, 2019: FEBS Journal
Wolfgang Doppler, Pidder Jansen-Dürr
Transformation by the ras oncogene can result in promotion of metastasis as well as induction of senescence via increased tissue remodeling, for example, by matrix metalloproteases. Increased production of mitochondrial reactive oxygen species (mtROS) via NADPH oxidase 4 (NOX4) is implicated in this process. Hydrogen peroxide-inducible clone-5 (HIC-5) is postulated to sense both matrix detachment of transformed cells and intracellular ROS and can inhibit ras signaling via inhibition of NOX4.
January 25, 2019: FEBS Journal
Tyler D R Vance, Maddalena Bayer-Giraldi, Peter L Davies, Marco Mangiagalli
Ice-binding proteins (IBPs) control the growth and shape of ice crystals to cope with sub-zero temperatures in psychrophilic and freeze-tolerant organisms. Recently, numerous proteins containing the domain of unknown function (DUF) 3494 were found to bind ice crystals and, hence, are classified as IBPs. DUF3494 IBPs constitute today the most widespread of the known IBP families. They can be found in different organisms including bacteria, yeasts and microalgae, supporting the hypothesis of horizontal transfer of its gene...
January 24, 2019: FEBS Journal
Nicolai Tidemand Johansen, Frederik Grønbaek Tidemand, Tam T T N Nguyen, Kasper Dyrberg Rand, Martin Cramer Pedersen, Lise Arleth
Recently, an enzymatic reaction was utilized to covalently link the N- and C-termini of membrane scaffold proteins to produce circularized nanodiscs that were more homogeneous and stable than standard nanodiscs. We continue this development and aim for obtaining high yields of stable and monodisperse nanodiscs for structural studies of membrane proteins by solution small-angle scattering techniques. Based on the template MSP1E3D1, we designed an optimized membrane scaffold protein (His-lsMSP1E3D1) with a sortase recognition-motif and high abundance of solubility-enhancing negative charges...
January 23, 2019: FEBS Journal
Shigeki Arai, Chie Shibazaki, Motoyasu Adachi, Yoshitake Maeda, Tomoyuki Tahara, Takashi Kato, Hiroshi Miyazaki, Ryota Kuroki
Human thrombopoietin (hTPO) is a primary hematopoietic growth factor that regulates megakaryocytopoiesis and platelet production. The non-glycosylated form of 1-163 residues of hTPO (hTPO163 ) including the N-terminal active site domain (1-153 residues) is a candidate for treating thrombocytopenia. However, the autoantigenicity level of hTPO163 is higher than that of the full-length glycosylated hTPO (ghTPO332 ). In order to clarify the structural and physicochemical properties of hTPO163 , circular dichroism (CD) and differential scanning calorimetry (DSC) analyses were performed...
January 23, 2019: FEBS Journal
Alessia Ruggiero, Giovanni Smaldone, Luciana Esposito, Nicole Balasco, Luigi Vitagliano
The definition of the structural basis of protein thermostability represents a major topic in structural biology and protein chemistry. We have recently observed that proteins isolated from thermophilic organisms show a better adherence to the fundamental rules of protein topology previously unveiled by Baker and coworkers (Koga et al. Nature. 2012 491:222-227). Here, we explored the possibility that ad hoc modifications of a natural protein following these rules could represent an efficient tool to stabilize its structure...
January 23, 2019: FEBS Journal
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