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FAD binding protein

Priyanka Dutta, Ahnaf Siddiqui, Mohsen Botlani, Sameer Varma
Nipah is an emerging paramyxovirus that is of serious concern to human health. It invades host cells using two of its membrane proteins-G and F. G binds to host ephrins and this stimulates G to activate F. Upon activation, F mediates virus-host membrane fusion. Here we focus on mechanisms that underlie the stimulation of G by ephrins. Experiments show that G interacts with ephrin and F through separate sites located on two different domains, the receptor binding domain (RBD) and the F activation domain (FAD)...
October 18, 2016: Biophysical Journal
Gina L O'Grady, Heather A Best, Tamar E Sztal, Vanessa Schartner, Myriam Sanjuan-Vazquez, Sandra Donkervoort, Osorio Abath Neto, Roger Bryan Sutton, Biljana Ilkovski, Norma Beatriz Romero, Tanya Stojkovic, Jahannaz Dastgir, Leigh B Waddell, Anne Boland, Ying Hu, Caitlin Williams, Avnika A Ruparelia, Thierry Maisonobe, Anthony J Peduto, Stephen W Reddel, Monkol Lek, Taru Tukiainen, Beryl B Cummings, Himanshu Joshi, Juliette Nectoux, Susan Brammah, Jean-François Deleuze, Viola Oorschot Ing, Georg Ramm, Didem Ardicli, Kristen J Nowak, Beril Talim, Haluk Topaloglu, Nigel G Laing, Kathryn N North, Daniel G MacArthur, Sylvie Friant, Nigel F Clarke, Robert J Bryson-Richardson, Carsten G Bönnemann, Jocelyn Laporte, Sandra T Cooper
This study establishes PYROXD1 variants as a cause of early-onset myopathy and uses biospecimens and cell lines, yeast, and zebrafish models to elucidate the fundamental role of PYROXD1 in skeletal muscle. Exome sequencing identified recessive variants in PYROXD1 in nine probands from five families. Affected individuals presented in infancy or childhood with slowly progressive proximal and distal weakness, facial weakness, nasal speech, swallowing difficulties, and normal to moderately elevated creatine kinase...
September 28, 2016: American Journal of Human Genetics
Andrea von Zadow, Elisabeth Ignatz, Richard Pokorny, Lars-Oliver Essen, Gabriele Klug
Photolyases are efficient DNA repair enzymes that specifically repair either cyclobutane pyrimidine dimers (CPD) or (6-4) photoproducts in a light-dependent cleavage reaction. The closely related classical cryptochrome blue light photoreceptors do not repair DNA lesions, instead they are involved in regulatory processes. CryB of Rhodobacter sphaeroides was until now described as a cryptochrome that affects light-dependent and singlet oxygen-dependent gene expression and is unusual in terms of its cofactor composition...
October 14, 2016: FEBS Journal
Qinghao Zhang, Cuihong You, Shuqi Wang, Yewei Dong, Óscar Monroig, Douglas R Tocher, Yuanyou Li
As the first marine teleost demonstrated to have the ability to biosynthesize long-chain polyunsaturated fatty acids (LC-PUFA) from C18 PUFA precursors, rabbitfish Siganus canaliculatus provides a good model for studying the regulatory mechanisms of LC-PUFA biosynthesis in teleosts. Here the potential roles of miR-33 in such regulation were investigated. The miR-33 gene was identified within intron 16 of the gene encoding sterol regulatory element-binding protein 1 (Srebp1), an activator of LC-PUFA biosynthesis...
2016: Scientific Reports
Ting-Hai Xu, Yan Yan, Yanyong Kang, Yi Jiang, Karsten Melcher, H Eric Xu
Mutations in the amyloid precursor protein (APP) gene and the aberrant cleavage of APP by γ-secretase are associated with Alzheimer's disease (AD). Here we have developed a simple and sensitive cell-based assay to detect APP cleavage by γ-secretase. Unexpectedly, most familial AD (FAD)-linked APP mutations make APP partially resistant to γ-secretase. Mutations that alter residues N terminal to the γ-secretase cleavage site Aβ42 have subtle effects on cleavage efficiency and cleavage-site selectivity. In contrast, mutations that alter residues C terminal to the Aβ42 site reduce cleavage efficiency and dramatically shift cleavage-site specificity toward the aggregation-prone Aβ42...
2016: Cell Discovery
Mengmeng Huang, Lingling Wang, Huan Zhang, Chuanyan Yang, Rui Liu, Jiachao Xu, Zhihao Jia, Linsheng Song
A C-type lectin of multiple CRDs (CfLec-4) from Chlamys farreri was selected to investigate the sequence variation and functional differentiation of its CRDs. Its four CRDs with EPD/LSD, EPN/FAD, EPN/LND and EPN/YND key motifs were recombined separately. The recombinant proteins of CRD1 and CRD2 (designated as rCRD1 and rCRD2) could bind LPS and mannan, while the recombinant proteins of CRD3 and CRD4 (designated as rCRD3 and rCRD4) could bind LPS, PGN, mannan and glucan. Moreover, rCRD3 displayed broad microbe binding spectrum towards Gram-positive bacteria Staphylococcus aureus and Micrococcus luteus, Gram-negative bacteria Escherichia coli and Vibrio anguillarum, as well as fungi Pichia pastoris and Yarrowia lipolytica...
August 31, 2016: Developmental and Comparative Immunology
Dwi Susanti, Usha Loganathan, Biswarup Mukhopadhyay
A recent report suggested that the thioredoxin-dependent metabolic regulation, which is widespread in all domains of life, existed in methanogenic archaea about 3.5 billion years ago. We now show that the respective electron delivery enzyme (thioredoxin reductase, TrxR), although structurally similar to flavin-containing NADPH-dependent TrxRs (NTR), lacked an NADPH-binding site and was dependent on reduced coenzyme F420 (F420H2), a stronger reductant with a mid-point redox potential (E(o')) of -360 mV; E(o') of NAD(P)H is -320 mV...
September 2, 2016: Journal of Biological Chemistry
Leonardo D Garma, Milagros Medina, André H Juffer
A total of six different structural alignment tools (TM-Align, TriangleMatch, CLICK, ProBis, SiteEngine and GA-SI) were assessed for their ability to perform two particular tasks: (i) discriminating FAD (flavin adenine dinucleotide) from non-FAD binding sites, and (ii) performing an all-to-all comparison on a set of 883 FAD binding sites with the purpose of classifying them. For the first task, the consistency of each alignment method was evaluated, showing that every method is able to distinguish FAD and non-FAD binding sites with a high Matthews correlation coefficient...
September 1, 2016: Proteins
Valerii Fedchenko, Arthur Kopylov, Nadezhda Kozlova, Olga Buneeva, Alexei Kaloshin, Victor Zgoda, Alexei Medvedev
BACKGROUND/AIMS: Renalase is a recently discovered flavoprotein involved in regulation of blood pressure. Altered renalase levels have been found in blood of patients with end stage renal disease. The antihypertensive effect of circulating renalase is attributed to putative FAD-dependent monoamine oxidase activity demonstrated by some authors. Being synthesized as an intracellular flavoprotein renalase requires the presence of its N-terminal peptide for FAD accommodation. However, conventional routes of export of secretory proteins outside the cell usually include cleavage of their N-terminal peptide...
2016: Kidney & Blood Pressure Research
Tobias M Hedison, Nicole G H Leferink, Sam Hay, Nigel S Scrutton
A major challenge in enzymology is the need to correlate the dynamic properties of enzymes with, and understand the impact on, their catalytic cycles. This is especially the case with large, multicenter enzymes such as the nitric oxide synthases (NOSs), where the importance of dynamics has been inferred from a variety of structural, single-molecule, and ensemble spectroscopic approaches but where motions have not been correlated experimentally with mechanistic steps in the reaction cycle. Here we take such an approach...
August 5, 2016: ACS Catalysis
Sarena Che Omar, Michael A Bentley, Giulia Morieri, Gail M Preston, Sarah J Gurr
The rice blast fungus causes significant annual harvest losses. It also serves as a genetically-tractable model to study fungal ingress. Whilst pathogenicity determinants have been unmasked and changes in global gene expression described, we know little about Magnaporthe oryzae cell wall remodelling. Our interests, in wall remodelling genes expressed during infection, vegetative growth and under exogenous wall stress, demand robust choice of reference genes for quantitative Real Time-PCR (qRT-PCR) data normalisation...
2016: PloS One
Chin-Yuan Chang, Jeremy R Lohman, Hongnan Cao, Kemin Tan, Jeffrey D Rudolf, Ming Ma, Weijun Xu, Craig A Bingman, Ragothaman M Yennamalli, Lance Bigelow, Gyorgy Babnigg, Xiaohui Yan, Andrzej Joachimiak, George N Phillips, Ben Shen
C-1027 is a chromoprotein enediyne antitumor antibiotic produced by Streptomyces globisporus. In the last step of biosynthesis of the (S)-3-chloro-5-hydroxy-β-tyrosine moiety of the C-1027 enediyne chromophore, SgcE6 and SgcC compose a two-component monooxygenase that hydroxylates the C-5 position of (S)-3-chloro-β-tyrosine. This two-component monooxygenase is remarkable for two reasons. (i) SgcE6 specifically reacts with FAD and NADH, and (ii) SgcC is active with only the peptidyl carrier protein (PCP)-tethered substrate...
September 13, 2016: Biochemistry
Li-Kai Liu, Heba Abdelwahab, Julia S Martin Del Campo, Ritcha Mehra-Chaudhary, Pablo Sobrado, John J Tanner
Rifampicin monooxygenase (RIFMO) catalyzes the N-hydroxylation of the natural product antibiotic rifampicin (RIF) to 2'-N-hydroxy-4-oxo-rifampicin, a metabolite with much lower antimicrobial activity. RIFMO shares moderate sequence similarity with well-characterized flavoprotein monooxygenases, but the protein has not been isolated and characterized at the molecular level. Herein, we report crystal structures of RIFMO from Nocardia farcinica, the determination of the oligomeric state in solution with small-angle X-ray scattering, and the spectrophotometric characterization of substrate binding...
August 24, 2016: Journal of Biological Chemistry
Iti Saraav, Kirti Pandey, Richa Misra, Swati Singh, Monika Sharma, Sadhna Sharma
Tuberculosis is a global health problem especially with emergence of drug resistant Mycobacterium tuberculosis strains, creating an urgent need to identify new drug targets. The mycobacterial cell wall is an attractive target for chemotherapeutic agents. Gene products of mymA operon are known to be required for maintenance of cell wall and play an important role in persistence, thus making them important drug targets. The present study was undertaken to biochemically characterize the MymA as a Flavin Containing Monooxygenase (FMO)...
August 19, 2016: Chemical Biology & Drug Design
Nguyen-Quoc-Khanh Le, Yu-Yen Ou
BACKGROUND: Cellular respiration is a catabolic pathway for producing adenosine triphosphate (ATP) and is the most efficient process through which cells harvest energy from consumed food. When cells undergo cellular respiration, they require a pathway to keep and transfer electrons (i.e., the electron transport chain). Due to oxidation-reduction reactions, the electron transport chain produces a transmembrane proton electrochemical gradient. In case protons flow back through this membrane, this mechanical energy is converted into chemical energy by ATP synthase...
2016: BMC Bioinformatics
Yewei Dong, Shuqi Wang, Junliang Chen, Qinghao Zhang, Yang Liu, Cuihong You, Óscar Monroig, Douglas R Tocher, Yuanyou Li
Rabbitfish Siganus canaliculatus was the first marine teleost demonstrated to have the capability of biosynthesizing long-chain polyunsaturated fatty acids (LC-PUFA) from C18 precursors, and to possess a Δ4 fatty acyl desaturase (Δ4 Fad) which was the first report in vertebrates, and is a good model for studying the regulatory mechanisms of LC-PUFA biosynthesis in teleosts. In order to understand regulatory mechanisms of transcription of Δ4 Fad, the gene promoter was cloned and characterized in the present study...
2016: PloS One
Janis J Füller, René Röpke, Joern Krausze, Kim E Rennhack, Nils P Daniel, Wulf Blankenfeldt, Stefan Schulz, Dieter Jahn, Jürgen Moser
Violacein is a natural purple pigment of Chromobacterium violaceum with potential medical applications as antimicrobial, antiviral, and anticancer drugs. The initial step of violacein biosynthesis is the oxidative conversion of l-tryptophan into the corresponding α-imine catalyzed by the flavoenzyme l-tryptophan oxidase (VioA). A substrate-related (3-(1H-indol-3-yl)-2-methylpropanoic acid) and a product-related (2-(1H-indol-3-ylmethyl)prop-2-enoic acid) competitive VioA inhibitor was synthesized for subsequent kinetic and x-ray crystallographic investigations...
September 16, 2016: Journal of Biological Chemistry
Qinghao Zhang, Cuihong You, Fang Liu, Wendi Zhu, Shuqi Wang, Dizhi Xie, Óscar Monroig, Douglas R Tocher, Yuanyou Li
Rabbitfish Siganus canaliculatus was the first marine teleost demonstrated to have the ability to biosynthesize C20-22 long-chain polyunsaturated fatty acid (LC-PUFA) from C18 PUFA precursors, which is generally absent or low in marine teleosts. Thus, understanding the molecular basis of LC-PUFA biosynthesis in rabbitfish will contribute to efforts aimed at optimizing LC-PUFA biosynthesis in teleosts, especially marine species. In the present study, the importance of the transcription factors liver X receptor (Lxr) and sterol regulatory element-binding protein 1 (Srebp1) in regulation of LC-PUFA biosynthesis in rabbitfish was investigated...
September 2016: Lipids
Yingchen Ju, Shuilong Tong, Yongxiang Gao, Wei Zhao, Qi Liu, Qiong Gu, Jun Xu, Liwen Niu, Maikun Teng, Huihao Zhou
l-amino acid oxidases/deaminases (LAAOs/LAADs) are a class of oxidoreductases catalyzing the oxidative deamination of l-amino acids to α-keto acids. They are widely distributed in eukaryotic and prokaryotic organisms, and exhibit diverse substrate specificity, post-translational modifications and cellular localization. While LAAOs isolated from snake venom have been extensively characterized, the structures and functions of LAAOs from other species are largely unknown. Here, we reported crystal structure of a bacterial membrane-bound LAAD from Proteus vulgaris (pvLAAD) in complex with flavin adenine dinucleotide (FAD)...
September 2016: Journal of Structural Biology
Panchanan Maiti, Tia C Hall, Leela Paladugu, Nivya Kolli, Cameron Learman, Julien Rossignol, Gary L Dunbar
Deposition of amyloid beta protein (Aβ) is a key component in the pathogenesis of Alzheimer's disease (AD). As an anti-amyloid natural polyphenol, curcumin (Cur) has been used as a therapy for AD. Its fluorescent activity, preferential binding to Aβ, as well as structural similarities with other traditional amyloid-binding dyes, make it a promising candidate for labeling and imaging of Aβ plaques in vivo. The present study was designed to test whether dietary Cur and nanocurcumin (NC) provide more sensitivity for labeling and imaging of Aβ plaques in brain tissues from the 5×-familial AD (5×FAD) mice than the classical Aβ-binding dyes, such as Congo red and Thioflavin-S...
November 2016: Histochemistry and Cell Biology
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