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Frontiers in Molecular Biosciences

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https://www.readbyqxmd.com/read/29354636/different-mechanisms-of-catalytic-complex-formation-in-two-l-tryptophan-processing-dioxygenases
#1
REVIEW
Karin Nienhaus, G Ulrich Nienhaus
The human heme enzymes tryptophan 2,3-dioxygenase (hTDO) and indoleamine 2,3 dioxygenase (hIDO) catalyze the initial step in L-tryptophan (L-Trp) catabolism, the insertion of dioxygen into L-Trp. Overexpression of these enzymes causes depletion of L-Trp and accumulation of metabolic products, and thereby contributes to tumor immune tolerance and immune dysregulation in a variety of disease pathologies. Understanding the assembly of the catalytically active, ternary enzyme-substrate-ligand complexes is not yet fully resolved, but an essential prerequisite for designing efficient and selective de novo inhibitors...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29326945/biochemical-properties-of-human-d-amino-acid-oxidase
#2
Giulia Murtas, Silvia Sacchi, Mattia Valentino, Loredano Pollegioni
D-amino acid oxidase catalyzes the oxidative deamination of D-amino acids. In the brain, the NMDA receptor coagonist D-serine has been proposed as its physiological substrate. In order to shed light on the mechanisms regulating D-serine concentration at the cellular level, we biochemically characterized human DAAO (hDAAO) in greater depth. In addition to clarify the physical-chemical properties of the enzyme, we demonstrated that divalent ions and nucleotides do not affect flavoenzyme function. Moreover, the definition of hDAAO substrate specificity demonstrated that D-cysteine is the best substrate, which made it possible to propose it as a putative physiological substrate in selected tissues...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29312956/transport-granules-bound-with-nuclear-cap-binding-protein-and-exon-junction-complex-are-associated-with-microtubules-and-spatially-separated-from-eif4e-granules-and-p-bodies-in-human-neuronal-processes
#3
Dan O Wang, Kensuke Ninomiya, Chihiro Mori, Ayako Koyama, Martine Haan, Makoto Kitabatake, Masatoshi Hagiwara, Kazuhiro Chida, Shin-Ichiro Takahashi, Mutsuhito Ohno, Naoyuki Kataoka
RNA transport and regulated local translation play critically important roles in spatially restricting gene expression in neurons. Heterogeneous population of RNA granules serve as motile units to translocate, store, translate, and degrade mRNAs in the dendrites contain cis-elements and trans-acting factors such as RNA-binding proteins and microRNAs to convey stimulus-, transcript-specific local translation. Here we report a class of mRNA granules in human neuronal processes that are enriched in the nuclear cap-binding protein complex (CBC) and exon junction complex (EJC) core components, Y14 and eIF4AIII...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29312955/theory-meets-experiment-metal-ion-effects-in-hcv-genomic-rna-kissing-complex-formation
#4
REVIEW
Li-Zhen Sun, Xiao Heng, Shi-Jie Chen
The long-range base pairing between the 5BSL3. 2 and 3'X domains in hepatitis C virus (HCV) genomic RNA is essential for viral replication. Experimental evidence points to the critical role of metal ions, especially Mg2+ ions, in the formation of the 5BSL3.2:3'X kissing complex. Furthermore, NMR studies suggested an important ion-dependent conformational switch in the kissing process. However, for a long time, mechanistic understanding of the ion effects for the process has been unclear. Recently, computational modeling based on the Vfold RNA folding model and the partial charge-based tightly bound ion (PCTBI) model, in combination with the NMR data, revealed novel physical insights into the role of metal ions in the 5BSL3...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29312954/biochemical-and-thermodynamical-characterization-of-glucose-oxidase-invertase-and-alkaline-phosphatase-secreted-by-antarctic-yeasts
#5
Yassef Yuivar, Salvador Barahona, Jennifer Alcaíno, Víctor Cifuentes, Marcelo Baeza
The use of enzymes in diverse industries has increased substantially over past decades, creating a well-established and growing global market. Currently, the use of enzymes that work better at ambient or lower temperatures in order to decrease the temperatures of production processes is desirable. There is thus a continuous search for enzymes in cold environments, especially from microbial sources, with amylases, proteases, lipases and, cellulases being the most studied. Other enzymes, such as glucose oxidase (GOD), invertase (Inv), and alkaline phosphatase (ALP), also have a high potential for application, but have been much less studied in microorganisms living in cold-environments...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29312953/chlorophyll-derivative-modulation-of-rhodopsin-signaling-properties-through-evolutionarily-conserved-interaction-pathways
#6
Kristina N Woods, Jürgen Pfeffer, Judith Klein-Seetharaman
Retinal is the light-absorbing chromophore that is responsible for the activation of visual pigments and light-driven ion pumps. Evolutionary changes in the intermolecular interactions of the retinal with specific amino acids allow for adaptation of the spectral characteristics, referred to as spectral tuning. However, it has been proposed that a specific species of dragon fish has bypassed the adaptive evolutionary process of spectral tuning and replaced it with a single evolutionary event: photosensitization of rhodopsin by chlorophyll derivatives...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29312952/combined-metabolomic-analysis-of-plasma-and-urine-reveals-ahba-tryptophan-and-serotonin-metabolism-as-potential-risk-factors-in-gestational-diabetes-mellitus-gdm
#7
Miriam Leitner, Lena Fragner, Sarah Danner, Nastassja Holeschofsky, Karoline Leitner, Sonja Tischler, Hannes Doerfler, Gert Bachmann, Xiaoliang Sun, Walter Jaeger, Alexandra Kautzky-Willer, Wolfram Weckwerth
Gestational diabetes mellitus during pregnancy has severe implications for the health of the mother and the fetus. Therefore, early prediction and an understanding of the physiology are an important part of prenatal care. Metabolite profiling is a long established method for the analysis and prediction of metabolic diseases. Here, we applied untargeted and targeted metabolomic protocols to analyze plasma and urine samples of pregnant women with and without GDM. Univariate and multivariate statistical analyses of metabolomic profiles revealed markers such as 2-hydroxybutanoic acid (AHBA), 3-hydroxybutanoic acid (BHBA), amino acids valine and alanine, the glucose-alanine-cycle, but also plant-derived compounds like sitosterin as different between control and GDM patients...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29302591/function-by-structure-spotlights-on-xist-long-non-coding-rna
#8
REVIEW
Greta Pintacuda, Alexander N Young, Andrea Cerase
Recent experimental evidence indicates that lncRNAs can act as regulatory molecules in the context of development and disease. Xist, the master regulator of X chromosome inactivation, is a classic example of how lncRNAs can exert multi-layered and fine-tuned regulatory functions, by acting as a molecular scaffold for recruitment of distinct protein factors. In this review, we discuss the methodologies employed to define Xist RNA structures and the tight interplay between structural clues and functionality of lncRNAs...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29270408/protein-translocation-into-the-intermembrane-space-and-matrix-of-mitochondria-mechanisms-and-driving-forces
#9
REVIEW
Sandra Backes, Johannes M Herrmann
Mitochondria contain two aqueous subcompartments, the matrix and the intermembrane space (IMS). The matrix is enclosed by both the inner and outer mitochondrial membranes, whilst the IMS is sandwiched between the two. Proteins of the matrix are synthesized in the cytosol as preproteins, which contain amino-terminal matrix targeting sequences that mediate their translocation through translocases embedded in the outer and inner membrane. For these proteins, the translocation reaction is driven by the import motor which is part of the inner membrane translocase...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29255714/mouse-d-amino-acid-oxidase-distribution-and-physiological-substrates
#10
REVIEW
Reiko Koga, Yurika Miyoshi, Hiroaki Sakaue, Kenji Hamase, Ryuichi Konno
d-Amino-acid oxidase (DAO) catalyzes the oxidative deamination of d-amino acids. DAO is present in a wide variety of organisms and has important roles. Here, we review the distribution and physiological substrates of mouse DAO. Mouse DAO is present in the kidney, brain, and spinal cord, like DAOs in other mammals. However, in contrast to other animals, it is not present in the mouse liver. Recently, DAO has been detected in the neutrophils, retina, and small intestine in mice. To determine the physiological substrates of mouse DAO, mutant mice lacking DAO activity are helpful...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29250527/competitive-inhibitors-unveil-structure-function-relationships-in-human-d-amino-acid-oxidase
#11
REVIEW
Gianluca Molla
D-amino acid oxidase (DAAO) catalyzes the oxidative deamination of several neutral D-amino acids and is the enzyme mainly responsible (together with serine racemase) for degrading D-serine (D-Ser) in the central nervous system of mammals. This D-amino acid, which binds the coagonist site of the N-methyl-D-aspartate receptor, is thus a key neuromodulator of glutamatergic neurotransmission. Altered D-Ser metabolism results in several pathological conditions (e.g., amylotrophic lateral sclerosis or schizophrenia, SZ) for which effective "broad spectrum" pharmaceutical drugs are not yet available...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29250526/mk-styx-alters-the-morphology-of-primary-neurons-and-outgrowths-in-mk-styx-overexpressing-pc-12-cells-develop-a-neuronal-phenotype
#12
Dallas A Banks, Arya Dahal, Alexander G McFarland, Brittany M Flowers, Christina A Stephens, Benjamin Swack, Ayele Gugssa, Winston A Anderson, Shantá D Hinton
We previously reported that the pseudophosphatase MK-STYX (mitogen activated kinase phosphoserine/threonine/tyrosine binding protein) dramatically increases the number of what appeared to be primary neurites in rat pheochromocytoma (PC-12) cells; however, the question remained whether these MK-STYX-induced outgrowths were bona fide neurites, and formed synapses. Here, we report that microtubules and microfilaments, components of the cytoskeleton that are involved in the formation of neurites, are present in MK-STYX-induced outgrowths...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29234667/a-matter-of-taste-lineage-specific-loss-of-function-of-taste-receptor-genes-in-vertebrates
#13
REVIEW
Marco Antinucci, Davide Risso
Vertebrates can perceive at least five different taste qualities, each of which is thought to have a specific role in the evolution of different species. The avoidance of potentially poisonous foods, which are generally bitter or sour tasting, and the search for more nutritious ones, those with high-fat and high-sugar content, are two of the most well-known examples. The study of taste genes encoding receptors that recognize ligands triggering taste sensations has helped to reconstruct several evolutionary adaptations to dietary changes...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29234666/technical-advances-to-study-extracellular-vesicles
#14
REVIEW
Paula Carpintero-Fernández, Juan Fafián-Labora, Ana O'Loghlen
Extracellular vesicles are a heterogeneous and dynamic group of lipid bilayer membrane nanoparticles that can be classified into three different groups depending on their cellular origin: exosomes, microvesicles, and apoptotic bodies. They are produced by different cell types and can be isolated from almost all body fluids. EVs contain a variety of proteins, lipids, nucleic acids, and metabolites which regulate a number of biological and pathological scenarios both locally and systemically. Different techniques have been described in order to determine EV isolation, release, uptake, and cargo...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29230394/acetylome-of-acinetobacter-baumannii-sk17-reveals-a-highly-conserved-modification-of-histone-like-protein-hu
#15
Jiahn-Haur Liao, Cheng-Han Tsai, Sanjay G Patel, Jhih-Tian Yang, I-Fan Tu, Matteo Lo Cicero, Magdalena Lipka-Lloyd, Wan-Ling Wu, Wen-Jie Shen, Meng-Ru Ho, Chi-Chi Chou, Garima R Sharma, Hiroki Okanishi, Louis Y P Luk, Yu-Hsuan Tsai, Shih-Hsiung Wu
Lysine acetylation is a prevalent post-translational modification in both eukaryotes and prokaryotes. Whereas this modification is known to play pivotal roles in eukaryotes, the function and extent of this modification in prokaryotic cells remain largely unexplored. Here we report the acetylome of a pair of antibiotic-sensitive and -resistant nosocomial pathogen Acinetobacter baumannii SK17-S and SK17-R. A total of 145 lysine acetylation sites on 125 proteins was identified, and there are 23 acetylated proteins found in both strains, including histone-like protein HU which was found to be acetylated at Lys13...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29214156/off-target-effects-of-drugs-that-disrupt-human-mitochondrial-dna-maintenance
#16
REVIEW
Matthew J Young
Nucleoside reverse transcriptase inhibitors (NRTIs) were the first drugs used to treat human immunodeficiency virus (HIV) the cause of acquired immunodeficiency syndrome. Development of severe mitochondrial toxicity has been well documented in patients infected with HIV and administered NRTIs. In vitro biochemical experiments have demonstrated that the replicative mitochondrial DNA (mtDNA) polymerase gamma, Polg, is a sensitive target for inhibition by metabolically active forms of NRTIs, nucleotide reverse transcriptase inhibitors (NtRTIs)...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29201867/inhibiting-dna-polymerases-as-a-therapeutic-intervention-against-cancer
#17
REVIEW
Anthony J Berdis
Inhibiting DNA synthesis is an important therapeutic strategy that is widely used to treat a number of hyperproliferative diseases including viral infections, autoimmune disorders, and cancer. This chapter describes two major categories of therapeutic agents used to inhibit DNA synthesis. The first category includes purine and pyrmidine nucleoside analogs that directly inhibit DNA polymerase activity. The second category includes DNA damaging agents including cisplatin and chlorambucil that modify the composition and structure of the nucleic acid substrate to indirectly inhibit DNA synthesis...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29184888/targeting-dna-replication-and-repair-for-the-development-of-novel-therapeutics-against-tuberculosis
#18
REVIEW
Michael A Reiche, Digby F Warner, Valerie Mizrahi
Mycobacterium tuberculosis is the etiological agent of tuberculosis (TB), an infectious disease which results in approximately 10 million incident cases and 1.4 million deaths globally each year, making it the leading cause of mortality from infection. An effective frontline combination chemotherapy exists for TB; however, this regimen requires the administration of four drugs in a 2 month long intensive phase followed by a continuation phase of a further 4 months with two of the original drugs, and is only effective for the treatment of drug-sensitive TB...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29184887/weak-molecular-interactions-in-clathrin-mediated-endocytosis
#19
REVIEW
Sarah M Smith, Michael Baker, Mary Halebian, Corinne J Smith
Clathrin-mediated endocytosis is a process by which specific molecules are internalized from the cell periphery for delivery to early endosomes. The key stages in this step-wise process, from the starting point of cargo recognition, to the later stage of assembly of the clathrin coat, are dependent on weak interactions between a large network of proteins. This review discusses the structural and functional data that have improved our knowledge and understanding of the main weak molecular interactions implicated in clathrin-mediated endocytosis, with a particular focus on the two key proteins: AP2 and clathrin...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29164132/conserved-molecular-mechanism-of-tyra-dehydrogenase-substrate-specificity-underlying-alternative-tyrosine-biosynthetic-pathways-in-plants-and-microbes
#20
Craig A Schenck, Yusen Men, Hiroshi A Maeda
L-Tyrosine (Tyr) is an aromatic amino acid synthesized de novo in plants and microbes. In animals, Tyr must be obtained through their diet or synthesized from L-phenylalanine. In addition to protein synthesis, Tyr serves as the precursor of neurotransmitters (e.g., dopamine and epinephrine) in animals and of numerous plant natural products, which serve essential functions in both plants and humans (e.g., vitamin E and morphine). Tyr is synthesized via two alternative routes mediated by a TyrA family enzyme, prephenate, or arogenate dehydrogenase (PDH/TyrAp or ADH/TyrAa), typically found in microbes and plants, respectively...
2017: Frontiers in Molecular Biosciences
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