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Federica Rigoldi, Stefano Donini, Francesca Giacomina, Federico Sorana, Alberto Redaelli, Tiziano Bandiera, Emilio Parisini, Alfonso Gautieri
Amadoriases are a class of FAD-dependent enzymes that are found in fungi, yeast and bacteria and that are able to hydrolyze glycated amino acids, cleaving the sugar moiety from the amino acidic portion. So far, engineered Amadoriases have mostly found practical application in the measurement of the concentration of glycated albumin in blood samples. However, these engineered forms of Amadoriases show relatively low absolute activity and stability levels, which affect their conditions of use. Therefore, enzyme stabilization is desirable prior to function-altering molecular engineering...
February 14, 2018: Scientific Reports
Michalina Wezyk, Aleksandra Szybinska, Joanna Wojsiat, Marcelina Szczerba, Kelly Day, Harriet Ronnholm, Malin Kele, Mariusz Berdynski, Beata Peplonska, Jakub Piotr Fichna, Jan Ilkowski, Maria Styczynska, Anna Barczak, Marzena Zboch, Anna Filipek-Gliszczynska, Krzysztof Bojakowski, Magdalena Skrzypczak, Krzysztof Ginalski, Michal Kabza, Izabela Makalowska, Maria Barcikowska-Kotowicz, Urszula Wojda, Anna Falk, Cezary Zekanowski
 The BRCA1 protein, one of the major players responsible for DNA damage response has recently been linked to Alzheimer's disease (AD). Using primary fibroblasts and neurons reprogrammed from induced pluripotent stem cells (iPSC) derived from familial AD (FAD) patients, we studied the role of the BRCA1 protein underlying molecular neurodegeneration. By whole-transcriptome approach, we have found wide range of disturbances in cell cycle and DNA damage response in FAD fibroblasts. This was manifested by significantly increased content of BRCA1 phosphorylated on Ser1524 and abnormal ubiquitination and subcellular distribution of presenilin 1 (PS1)...
2018: Journal of Alzheimer's Disease: JAD
Qiuyan Li, Kexian Dong, Lidan Xu, Xueyuan Jia, Jie Wu, Wenjing Sun, Xuelong Zhang, Songbin Fu
BACKGROUND: Heilongjiang Province located in northeast China is a multi-ethnic region with people who have lived in cold conditions for several generations. Fatty acids are important to people with cold resistance. CPT1A encodes a protein that imports long-chain fatty acids into the mitochondria for fatty-acid oxidation. FADS is an essential enzyme for the synthesis of long-chain polyunsaturated fatty acids. RESULTS: In the present study, we investigated the distributions of three cold resistance-related SNPs (rs80356779 G > A in CPT1A, rs7115739 T > G in FADS3 and rs174570 C > T in FADS2) from six populations that included 1093 individuals who have lived in Heilongjiang Province for at least three generations...
February 12, 2018: BMC Genomics
Yulan Shi, Xiule Yue, Lizhe An
Ω-3 fatty acid desaturases (FADs) are thought to contribute to plant stress tolerance mainly through the C18:3-induced membrane stabilization, but the comprehensive analysis of their roles in stress adaptation is lacking. Here, we isolated a microsomal ω-3 FAD gene (CbFAD3) from a cryophyte (Chorispora bungeana), and elucidated its functions in stress tolerance. CbFAD3, exhibiting highest identity to Arabidopsis AtFAD3, was up-regulated by abiotic stresses. Its functionality was verified by heterogonous expression in yeast...
February 8, 2018: Journal of Experimental Botany
Sangwoo Kim, Kyung-Jin Kim
Acyl-CoA oxidases (ACOXs) play important roles in lipid metabolism, including peroxisomal fatty acid β-oxidation by the conversion of acyl-CoAs to 2-trans-enoyl-CoAs. The yeast Yarrowia lipolyticacan utilize fatty acidsas a carbon source and thus has extensive biotechnological applications. The crystal structure of ACOX3from Y. lipolytica(YlACOX3) was determinedat a resolution of2.5 Å. It contained two molecules per asymmetric unit, and the monomeric structure was folded into four domains, Nα, Nβ, Cα1 and Cα2domains...
February 13, 2018: Journal of Microbiology and Biotechnology
Marco Salomone-Stagni, Joseph D Bartho, Ivan Polsinelli, Dom Bellini, Martin A Walsh, Nicola Demitri, Stefano Benini
The Gram-negative bacterium Erwinia amylovora is the etiological agent of fire blight, a devastating disease which affects Rosaceae such as apple, pear and quince. The siderophore desferrioxamine E plays an important role in bacterial pathogenesis by scavenging iron from the host. DfoJ, DfoA and DfoC are the enzymes responsible for desferrioxamine production starting from lysine. We have determined the crystal structures of each enzyme in the desferrioxamine E pathway and demonstrate that the biosynthesis involves the concerted action of DfoJ, followed by DfoA and lastly DfoC...
February 8, 2018: Journal of Structural Biology
Naveen Thakur, Ashwani Kumar, Kanak L Dikshit
Two distantly related flavohemoglobins (FHbs), MsFHbI and MsFHbII, having crucial differences in their heme and reductase domains, co-exist in Mycobacterium smegmatis. Function of MsFHbI is associated with nitric-oxide detoxification but physiological relevance of MsFHbII remains unknown. This study unravels some unique spectral and functional characteristics of MsFHbII. Unlike conventional type I FHbs, MsFHbII lacks nitric-oxide dioxygenase and NADH oxidase activities but utilizes d-lactate as an electron donor to mediate electron transfer...
February 8, 2018: International Journal of Biological Macromolecules
Hui Gyu Park, Matthew G Engel, Kyle Vogt-Lowell, Peter Lawrence, Kumar S Kothapalli, J Thomas Brenna
INTRODUCTION: In mammals, FADS2 catalyzes "front-end" Δ4-, Δ6-, and Δ8-desaturation of fatty acyl chains, whereas FADS1 has Δ5-desaturase activity. Eighteen and 20-carbon precursors to highly unsaturated n-3 and n-6 fatty acids are the usual substrates for FADS1 and FADS2. Our main objective was to characterize the metabolic fate of oleic acid (OA) due to action of FADS gene products. METHODS: MCF-7 cells were stably transformed with either FADS1 or FADS2 or empty vector...
January 2018: Prostaglandins, Leukotrienes, and Essential Fatty Acids
Nina Timmerby, Fiammetta Cosci, Maggie Watson, Claudio Csillag, Florence Schmitt, Barbara Steck, Per Bech, Mikael Thastum
BACKGROUND: The Family Assessment Device (FAD) is a 60-item questionnaire widely used to evaluate self-reported family functioning. However, the factor structure as well as the number of items has been questioned. A shorter and more user-friendly version of the original FAD-scale, the 36-item FAD, has therefore previously been proposed, based on findings in a nonclinical population of adults. AIMS: We aimed in this study to evaluate the brief 36-item version of the FAD in a clinical population...
February 7, 2018: Nordic Journal of Psychiatry
Cen Zhang, Rui Wang, Guowen Zhang, Deming Gong
Quercetin, one of the most abundant flavonoid in the daily diet, was found to reversibly inhibit the generation of uric acid and superoxide radicals (O2-)catalyzed by xanthine oxidase (XOD) in a mixed-type manner with IC50 values of (2.74±0.04)×10-6 and (2.90±0.03)×10-6molL-1, respectively, and the inhibition of quercetin on O2- generation may be ascribed to the reduced form of XOD by a ping-pong mechanism. XOD had one high affinity binding site for quercetin with a binding constant of 4.28×104Lmol-1 at 298K, and the binding process was predominately driven by van der Waals forces and hydrogen bonds on account of the negative enthalpy and entropy changes...
January 31, 2018: International Journal of Biological Macromolecules
Stanislav Sutovsky, Tomas Smolek, Peter Turcani, Robert Petrovic, Petra Brandoburova, Santosh Jadhav, Petr Novak, Johannes Attems, Norbert Zilka
The majority (~ 55%) of early onset familial Alzheimer disease (FAD) is caused by mutations in the presenilin 1 gene (PSEN1). Here, we describe a family with early onset FAD with a missense mutation in the PSEN1 gene (Thr116Asn). Five family members developed dementia in the third decade of life. One subject underwent autopsy. The onset of clinical symptoms was at the age of 37 years and the disease progressed rapidly. The clinical picture was characterised by progressive memory impairment, amnestic aphasia, and gait disturbances...
February 5, 2018: Journal of Neural Transmission
Tetsuo Yamashita, Daniel Ken Inaoka, Tomoo Shiba, Takumi Oohashi, So Iwata, Takao Yagi, Hiroaki Kosaka, Hideto Miyoshi, Shigeharu Harada, Kiyoshi Kita, Katsuya Hirano
Yeast Ndi1 is a monotopic alternative NADH dehydrogenase. Its crystal structure in complex with the electron acceptor, ubiquinone, has been determined. However, there has been controversy regarding the ubiquinone binding site. To address these points, we identified the first competitive inhibitor of Ndi1, stigmatellin, along with new mixed-type inhibitors, AC0-12 and myxothiazol, and thereby determined the crystal structures of Ndi1 in complexes with the inhibitors. Two separate binding sites of stigmatellin, STG-1 and STG-2, were observed...
February 5, 2018: Scientific Reports
Manuel Benedetti, Ilaria Verrascina, Daniela Pontiggia, Federica Locci, Benedetta Mattei, Giulia De Lorenzo, Felice Cervone
Recognition of endogenous molecules acting as "damage-associated molecular patterns" (DAMPs) is a key feature of immunity in both animals and plants. Oligogalacturonides (OGs), i.e. fragments derived from the hydrolysis of homogalacturonan, a major component of pectin are a well-known class of DAMPs that activate immunity and protect plants against several microbes. However, hyper-accumulation of OGs severely affects growth, eventually leading to cell death and clearly pointing to OGs as players in the growth-defence trade-off...
February 3, 2018: Plant Journal: for Cell and Molecular Biology
A O Gwendolen Jull
No abstract text is available yet for this article.
January 29, 2018: Musculoskeletal Science & Practice
Kaifeng Li, Lorraine Brennan, Jack F Bloomfield, Dan J Duff, Breige A McNulty, Albert Flynn, JanetteMichael J WaltonGibney, Anne P Nugent
SCOPE: This study examined to what extent plasma linoleic acid (LA) is modified by adiposity, and explored any association between plasma LA, demographics, dietary intakes, markers of metabolic health and haplotypes of the fatty acid desaturase (FADS) 1/2 genes. METHODS AND RESULTS: 820 participants with fasting blood samples from Irish National Adult Nutrition Survey were studied. Plasma fatty acids were determined using GC-MS. 15 SNPs of FADS 1/2 genes were genotyped...
February 1, 2018: Molecular Nutrition & Food Research
Jin-Lian Ma, Ting Zhang, Feng-Zhi Suo, Jiao Chang, Xiang-Bin Wan, Xue-Jian Feng, Yi-Chao Zheng, Hong-Min Liu
B vitamins play an essential role in the biosynthesis of nucleotides, replication of DNA, supply of methyl-groups, growth and repair of cells, aberrancies of which have all been implicated in carcinogenesis. Although the potential role of vitamin B in relation to the risk of cancer, including breast and colorectal cancer, has been investigated in several observational studies, the mechanism of action is still unclear. In this study, vitamin B2 exhibited efficient activation of LSD1 by occupying the active sites where FAD stands...
January 31, 2018: Journal of Cellular Biochemistry
Salah Uddin Khan, Terri L O'Sullivan, Zvonimir Poljak, Janet Alsop, Amy L Greer
BACKGROUND: Infectious diseases in farmed animals have economic, social, and health consequences. Foreign animal diseases (FAD) of swine are of significant concern. Mathematical and simulation models are often used to simulate FAD outbreaks and best practices for control. However, simulation outcomes are sensitive to the population structure used. Within Canada, access to individual swine farm population data with which to parameterize models is a challenge because of privacy concerns...
January 30, 2018: BMC Veterinary Research
Maria Luisa Corrado, Tanja Knaus, Francesco Mutti
The styrene monooxygenase (SMO) system from Pseudomonas sp. is constituted by two enzymes (StyA and StyB). StyB catalyses the reduction of FAD at the expense of NADH. After the transfer of FADH2 from StyB to StyA, reaction with O2 generates FAD-OOH that is the epoxidising agent. The waste of redox equivalents due to a partial diffusive transfer of FADH2, the insolubility of recombinant StyB and the impossibility to express StyA and StyB in a 1:1 molar ratio reduce the catalytic efficiency of the natural system...
January 29, 2018: Chembiochem: a European Journal of Chemical Biology
Senwen Deng, Ping Li, Yiping Wang, Jia Zeng
Acyl-coA oxidase (ACO) is an important flavoenzyme responsible for the first step of peroxisomal fatty acid β-oxidation. In this study, the roles of Tyr232 and Tyr401 in flavin adenine dinucleotide (FAD) binding and enzyme catalysis of ACO were explored using site-directed mutagenesis. For mutant proteins, different levels of activity loss were observed. Wavelength scanning of Y232 and Y401 mutant proteins indicated that there is no FAD binding in Y401S and Y401G mutant ACO. Structure analysis indicated that the phenolic hydroxyl and benzene ring of the side chain could stabilize FAD binding through hydrogen bonds network and hydrophobic pocket formation...
January 25, 2018: Applied Biochemistry and Biotechnology
Cai You, Changshui Liu, Yingjie Li, Peng Jiang, Qingjun Ma
Rapid accumulations of unattached green macroalgae, referred to as blooms, constitute ecological disasters and occur in many coastal regions. Ulva are a major cause of blooms, owing to their high nitrogen utilization capacity, which requires nitrate reductase (NR) activity; however, molecular characterization of Ulva NR remains lacking. Herein we determined the crystal structure and performed an enzymatic analysis of the cytochrome b5 reductase domain of Ulva prolifera NR (UpCbRNR). The structural analysis revealed an N-terminal FAD-binding domain primarily consisting of six antiparallel β strands, a C-terminal NADH-binding domain forming a Rossmann fold, and a three β-stranded linker region connecting these two domains...
January 22, 2018: International Journal of Biological Macromolecules
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