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https://www.readbyqxmd.com/read/28640638/enzyme-mediated-conversion-of-fad-to-8-formyl-fad-in-formate-oxidase-results-in-modified-cofactor-with-enhanced-catalytic-properties
#1
John M Robbins, Michael G Souffrant, Donald Hamelberg, Giovanni Gadda, Andreas S Bommarius
Flavins, including flavin adenine dinucleotide (FAD), are fundamental catalytic cofactors responsible for the redox functionality of a diverse set of proteins. Alternatively, modified flavin analogues are rarely found in nature as their incorporation typically results in inactivation of flavoproteins, thus leading to the disruption of important cellular pathways. Here, we report that the fungal flavoenzyme formate oxidase (FOX) catalyzes the slow conversion of non-covalently bound FAD to 8-formyl FAD (8-fFAD), and that this conversion results in a nearly 10-fold increase in formate oxidase activity...
June 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/28640584/spectroscopic-evidence-for-a-h-bond-network-at-y356-located-at-the-subunit-interface-of-active-e-coli-ribonucleotide-reductase
#2
Thomas U Nick, Kanchana R Ravichandran, JoAnne Stubbe, Müge Kasanmascheff, Marina Bennati
The reaction catalyzed by E. coli ribonucleotide reductase (RNR) composed of α and β subunits that form an active α2β2 complex is a paradigm for proton-coupled electron transfer (PCET) processes in biological transformations. β2 contains the diferric tyrosyl radical (Y122•) cofactor that initiates a radical transfer (RT) over 35 Å via a specific pathway of amino acids (Y122• ↔ [W48] ↔ Y356 in β2 to Y731 ↔Y730↔ C439 in α2). Experimental evidence exists for co-linear and orthogonal PCET in α2 and β2 respectively...
June 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/28636325/challenges-and-hallmarks-of-establishing-alkylacetylphosphonates-as-probes-of-bacterial-1-deoxy-d-xylulose-5-phosphate-synthase
#3
Sara Sanders, Ryan J Vierling, David Bartee, Alicia A DeColli, Mackenzie J Harrison, Joseph L Aklinski, Andrew T Koppisch, Caren L Freel Meyers
1-Deoxy-d-xylulose 5-phosphate (DXP) synthase catalyzes the thiamin diphosphate (ThDP)-dependent formation of DXP from pyruvate and d-glyceraldehyde 3-phosphate. DXP is at a metabolic branch point in bacteria, feeding into the methylerythritol phosphate pathway to indispensable isoprenoids and acting as a precursor for biosynthesis of essential cofactors in central metabolism, pyridoxal phosphate and ThDP, the latter of which is also required for DXP synthase catalysis. DXP synthase follows a unique random sequential mechanism and possesses an unusually large active site...
June 21, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28636006/copper-ion-interaction-with-the-rnase-catalytic-site-fragment-of-the-angiogenin-protein-an-experimental-and-theoretical-investigation
#4
Antonio Magrì, Giovanni Tabbì, Raffaella Breglia, Luca De Gioia, Piercarlo Fantucci, Maurizio Bruschi, Raffaele P Bonomo, Diego La Mendola
The angiogenin protein (Ang) is a member of the vertebrate-specific secreted ribonucleases and one of the most potent angiogenic factors known. Ang is a normal constituent of human plasma and its concentration increases under some physiological and pathological conditions to promote neovascularization. Ang was originally identified as an angiogenic tumour factor, but its biological activity has been found to extend from inducing angiogenesis to promoting cell survival in different neurodegenerative diseases...
June 21, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28635963/single-molecule-analysis-of-steroid-receptor-and-cofactor-action-in-living-cells
#5
Ville Paakinaho, Diego M Presman, David A Ball, Thomas A Johnson, R Louis Schiltz, Peter Levitt, Davide Mazza, Tatsuya Morisaki, Tatiana S Karpova, Gordon L Hager
Population-based assays have been employed extensively to investigate the interactions of transcription factors (TFs) with chromatin and are often interpreted in terms of static and sequential binding. However, fluorescence microscopy techniques reveal a more dynamic binding behaviour of TFs in live cells. Here we analyse the strengths and limitations of in vivo single-molecule tracking and performed a comprehensive analysis on the intranuclear dwell times of four steroid receptors and a number of known cofactors...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28635300/pyridine-dinucleotides-from-molecules-to-man
#6
Joshua P Fessel, William M Oldham
SIGNIFICANCE: Pyridine dinucleotides, NAD and NADP, were discovered over 100 years ago as necessary cofactors for fermentation in yeast extracts. Since that time, these molecules have been recognized as fundamental players in a variety of cellular processes, including energy metabolism, redox homeostasis, cellular signaling, and gene transcription, among many others. Given their critical role as mediators of cellular responses to metabolic perturbations, it is unsurprising that dysregulation of NAD and NADP metabolism has been associated with the pathobiology of many chronic human diseases...
June 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28635184/design-synthesis-and-biological-evaluation-of-isothiosemicarbazones-with-antimycobacterial-activity
#7
Eva Novotná, Karel Waisser, Jiří Kuneš, Karel Palát, Lenka Skálová, Barbora Szotáková, Vladimír Buchta, Jiřina Stolaříková, Vít Ulmann, Marcela Pávová, Jan Weber, Jitka Komrsková, Pavlína Hašková, Ivan Vokřál, Vladimír Wsól
A series of benzaldehyde and salicylaldehyde-S-benzylisothiosemicarbazones was synthesized and tested against 12 different strains of mycobacteria, Gram-positive and Gram-negative bacteria, and the significant selectivity toward mycobacteria was proved. Twenty-eight derivatives were evaluated for the inhibition of isocitrate lyase, which is a key enzyme of the glyoxylate cycle necessary for latent tuberculosis infection, and their iron-chelating properties were investigated. Two derivatives, 5-bromosalicylaldehyde-S-(4-fluorobenzyl)-isothiosemicarbazone and salicylaldehyde-S-(4-bromobenzyl)-isothiosemicarbazone, influenced the isocitrate lyase activity and caused a better inhibition at 10 μmol/L than 3-nitropropionic acid, a standard inhibitor...
June 21, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28634302/structure-of-human-fe-s-assembly-subcomplex-reveals-unexpected-cysteine-desulfurase-architecture-and-acyl-acp-isd11-interactions
#8
Seth A Cory, Jonathan G Van Vranken, Edward J Brignole, Shachin Patra, Dennis R Winge, Catherine L Drennan, Jared Rutter, David P Barondeau
In eukaryotes, sulfur is mobilized for incorporation into multiple biosynthetic pathways by a cysteine desulfurase complex that consists of a catalytic subunit (NFS1), LYR protein (ISD11), and acyl carrier protein (ACP). This NFS1-ISD11-ACP (SDA) complex forms the core of the iron-sulfur (Fe-S) assembly complex and associates with assembly proteins ISCU2, frataxin (FXN), and ferredoxin to synthesize Fe-S clusters. Here we present crystallographic and electron microscopic structures of the SDA complex coupled to enzyme kinetic and cell-based studies to provide structure-function properties of a mitochondrial cysteine desulfurase...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28634178/ascorbate-protects-the-di-heme-enzyme-maug-against-self-inflicted-oxidative-damage-by-an-unusual-antioxidant-mechanism
#9
Zhongxin Ma, Victor L Davidson
Ascorbate protects MauG from self-inactivation that occurs during the autoreduction of the reactive bis -Fe(IV) state of its diheme cofactor. The mechanism of protection does not involve direct reaction with reactive oxygen species in solution. Instead it binds to MauG and mitigates oxidative damage that occurs via internal transfer of electrons from amino acid residues within the protein to the high-valent hemes. The presence of ascorbate does not inhibit the natural catalytic reaction of MauG which catalyzes oxidative posttranslational modifications of a substrate protein that binds to the surface of MauG, and is oxidized by the high-valent hemes via long range electron transfer...
June 20, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28633667/hpv-and-cofactors-for-invasive-cervical-cancer-in-morocco-a-multicentre-case-control-study
#10
Mohamed Berraho, Afaf Amarti-Riffi, Mohammed El-Mzibri, Rachid Bezad, Noureddine Benjaafar, Abdelatif Benideer, Noureddine Matar, Zinab Qmichou, Naima Abda, Mohammed Attaleb, Kaoutar Znati, Hind El Fatemi, Karima Bendahhou, Majdouline Obtel, Abdelhai Filali Adib, Simone Mathoulin-Pelissier, Chakib Nejjari
BACKGROUND: Limited national information is available in Morocco on the prevalence and distribution of HPV-sub-types of cervical cancer and the role of other risk factors. The aim was to determine the frequency of HPV-sub-types of cervical cancer in Morocco and investigate risk factors for this disease. METHODS: Between November 2009 and April 2012 a multicentre case-control study was carried out. A total of 144 cases of cervical cancer and 288 age-matched controls were included...
June 20, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28633311/cofactor-specificity-switch-in-shikimate-dehydrogenase-by-rational-design-and-consensus-engineering
#11
Fernando García-Guevara, Iris Bravo, Claudia Martínez-Anaya, Lorenzo Segovia
Consensus engineering has been used to design more stable variants using the most frequent amino acid at each site of a multiple sequence alignment; sometimes consensus engineering modifies function, but efforts have mainly been focused on studying stability. Here we constructed a consensus Rossmann domain for the Shikimate dehydrogenase enzyme; separately we decided to switch the cofactor specificity through rational design in the Escherichia coli Shikimate dehydrogenase enzyme and then analyzed the effect of consensus mutations on top of our design...
June 13, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28633062/blue-light-induced-reactive-oxygen-species-from-flavin-mononucleotide-and-flavin-adenine-dinucleotide-on-lethality-of-hela-cells
#12
Ming-Yeh Yang, Chih-Jui Chang, Liang-Yü Chen
Photodynamic therapy (PDT) is a safe and non-invasive treatment for cancers and microbial infections. Various photosensitizers and light sources have been developed for clinical cancer therapies. Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are the cofactor of enzymes and are used as photosensitizers in this study. Targeting hypoxia and light-triggering reactive oxygen species (ROS) are experimental strategies for poisoning tumor cells in vitro. HeLa cells are committed to apoptosis when treated with FMN or FAD and exposed to visible blue light (the maximum emitted wavelength of blue light is 462nm)...
June 13, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28632925/a-kallikrein-targeting-rna-aptamer-inhibits-the-intrinsic-pathway-of-coagulation-and-reduces-bradykinin-release
#13
K-A Steen-Burrell, J Layzer, B A Sullenger
BACKGROUND: Plasma kallikrein is a serine protease that plays an integral role in many biological processes including coagulation, inflammation, and fibrinolysis. The main function of kallikrein in coagulation is the amplification of activated factor XIIa (FXIIa) generation which ultimately leads to thrombin generation and fibrin clot formation. Kallikrein is generated by FXIIa-mediated cleavage of the zymogen, prekallikrein which is usually complexed with the nonenzymatic cofactor, high-molecular-weight kininogen (HK)...
June 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28630323/role-of-the-cbp-catalytic-core-in-intramolecular-sumoylation-and-control-of-histone-h3-acetylation
#14
Sangho Park, Robyn L Stanfield, Maria A Martinez-Yamout, H Jane Dyson, Ian A Wilson, Peter E Wright
The histone acetyl transferases CREB-binding protein (CBP) and its paralog p300 play a critical role in numerous cellular processes. Dysregulation of their catalytic activity is associated with several human diseases. Previous work has elucidated the regulatory mechanisms of p300 acetyltransferase activity, but it is not known whether CBP activity is controlled similarly. Here, we present the crystal structure of the CBP catalytic core encompassing the bromodomain (BRD), CH2 (comprising PHD and RING), HAT, and ZZ domains at 2...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630292/tetrahydrobiopterin-regulates-monoamine-neurotransmitter-sulfonation
#15
Ian Cook, Ting Wang, Thomas S Leyh
Monoamine neurotransmitters are among the hundreds of signaling small molecules whose target interactions are switched "on" and "off" via transfer of the sulfuryl-moiety (-SO3) from PAPS (3'-phosphoadenosine 5'-phosphosulfate) to the hydroxyls and amines of their scaffolds. These transfer reactions are catalyzed by a small family of broad-specificity enzymes-the human cytosolic sulfotransferases (SULTs). The first structure of a SULT allosteric-binding site (that of SULT1A1) has recently come to light. The site is conserved among SULT1 family members and is promiscuous-it binds catechins, a naturally occurring family of flavanols...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630126/a-key-enzyme-of-the-nad-salvage-pathway-in-thermus-thermophilus-characterization-of-nicotinamidase-and-the-impact-of-its-gene-deletion-at-high-temperatures
#16
Hironori Taniguchi, Sathidaphorn Sungwallek, Phatcharin Chotchuang, Kenji Okano, Kohsuke Honda
Nicotinamide adenine dinucleotide (NAD(+)) is a cofactor related to many cellular processes. This cofactor is known to be unstable, especially at high temperatures, where it chemically decomposes to nicotinamide and ADP-ribose. Bacteria, yeast, and higher organisms possess the salvage pathway for reconstructing NAD(+) from these decomposition products; however, the importance of the salvage pathway for survival is not well elucidated, except for in pathogens lacking the NAD(+)de novo synthesis pathway. Herein, we report the importance of the NAD(+) salvage pathway in the thermophilic bacterium Thermus thermophilus HB8 at high temperatures...
June 19, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28629859/s-adenosyl-l-homocysteine-hydrolase-from-a-hyperthermophile-thermotoga-maritima-is-expressed-in-escherichia-coli-in-inactive-form-biochemical-and-structural-studies
#17
Krzysztof Brzezinski, Justyna Czyrko, Joanna Sliwiak, Edyta Nalewajko-Sieliwoniuk, Mariusz Jaskolski, Boguslaw Nocek, Zbigniew Dauter
Thermotoga maritima is a hyperthermophilic bacterium but its genome encodes a number of archaeal proteins including S-adenosyl-L-homocysteine hydrolase (SAHase), which regulates cellular methylation reactions. The question of proper folding and activity of proteins of extremophilic origin is an intriguing problem. When expressed in E.coli and purified (as a homotetramer) at room temperature, the hyperthermophilic SAHase from T.maritima was inactive. ITC study indicated that the protein undergoes heat-induced conformational changes, and enzymatic activity assays demonstrated that these changes are required to attain enzymatic activity...
June 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28628799/a-novel-2-stage-approach-that-detects-complement-activation-in-patients-with-antiphospholipid-antibody-syndrome
#18
Jacob H Rand, Xiao-Xuan Wu, Lucia R Wolgast, Victor Lei, Edward M Conway
INTRODUCTION: The antiphospholipid syndrome (APS) is marked by autoantibodies that recognize anionic phospholipids in a cofactor-dependent manner. A role for complement has been implicated in the pathophysiology, however, elevations of complement activation markers have not been consistently demonstrated in clinical studies. We therefore designed a proof-of-principle study to determine whether complement activation might be detectable in APS by first exposing plasmas to phospholipid vesicles...
June 9, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28628687/the-infatuation-with-biotin-supplementation-is-there-truth-behind-its-rising-popularity-a-comparative-analysis-of-clinical-efficacy-versus-social-popularity
#19
Teo Soleymani, Kristen Lo Sicco, Jerry Shapiro
<p>Biotin, also known as Vitamin B7 or vitamin H, is a water-soluble B vitamin that acts as an essential cofactor for several carboxylases involved in the cellular metabolism of fatty acids, amino acids, and gluconeogenesis. Although there exists an incredible amount of social media hype and market advertising touting its efficacy for the improvement of hair quantity and quality, biotin's efficacy for hair remains largely unsubstantiated in scientific literature. We reviewed all pertinent scientific literature regarding the efficacy of biotin supplementation for hair growth and quality improvement, and we also investigated its popularity in society defined as a function of market analytics...
May 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28625351/challenges-of-non-flocculating-saccharomyces-cerevisiae-haploid-strain-against-inhibitory-chemical-complex-for-ethanol-production
#20
Prihardi Kahar, Eny Ida Riyanti, Hiromi Otsuka, Hana Matsumoto, Chie Kihira, Chiaki Ogino, Akihiko Kondo
This study provides insight observation based on the gene expression and the metabolomic analysis of the natural robust yeast Saccharomyces cerevisiae NBRC849 during the fermentation in the medium containing inhibitory chemical complexes (ICC) at different concentrations. The tolerance mechanisms involved in the strain might have existed through the upregulation of genes involved in NAD(H)/NADP(H) cofactors generations (ALD6, ZWF1, GND1), membrane robustness for efflux pump (YOR1, PDR5, TPO3) and cation/polyamine transport (TPO3)...
June 15, 2017: Bioresource Technology
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