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https://www.readbyqxmd.com/read/30341796/crystal-structure-of-adomet-radical-enzyme-7-carboxy-7-deazaguanine-synthase-from-escherichia-coli-suggests-how-modifications-near-4fe-4s-cluster-engender-flavodoxin-specificity
#1
Tsehai A J Grell, Benjamin N Bell, Chi Nguyen, Daniel P Dowling, Nathan A Bruender, Vahe Bandarian, Catherine L Drennan
7-carboxy-7-deazaguanine synthase, QueE, catalyzes the radical mediated ring contraction of 6-carboxy-5,6,7,8-tetrahydropterin, forming the characteristic pyrrolopyrimidine core of all 7-deazaguanine natural products. QueE is a member of the S-adenosyl-L-methionine (AdoMet) radical enzyme superfamily, which harnesses the reactivity of radical intermediates to perform challenging chemical reactions. Members of the AdoMet radical enzyme superfamily utilize a canonical binding motif, a CX3 CXφC motif, to bind a [4Fe-4S] cluster and a partial (β/α)6 TIM barrel fold for the arrangement of AdoMet and substrates for catalysis...
October 19, 2018: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/30334285/improved-activity-of-%C3%AE-l-arabinofuranosidase-from-geobacillus-vulcani-gs90-by-directed-evolution-investigation-on-thermal-and-alkaline-stability
#2
Yusuf Sürmeli, Hüseyin İlgü, Gülşah Şanlı-Mohamed
α-L-arabinofuranosidase (Abf) is a potential enzyme because of its synergistic effect with other hemicellulases in agro-industrial field. In this study, directed evolution was applied to Abf from Geobacillus vulcani GS90 (GvAbf) using one round error-prone PCR and constructed a library of 73 enzyme variants of GvAbf. The activity screening of the enzyme variants was performed on soluble protein extracts using p-nitrophenyl α-L-arabinofuranoside as substrate. Two high activity displaying variants (GvAbf L307S and GvAbf Q90H/L307S) were selected, purified, partially characterized and structurally analysed...
October 17, 2018: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/30289978/lkb1-regulates-prmt5-activity-in-breast-cancer
#3
Hanine Lattouf, Loay Kassem, Julien Jacquemetton, Ali Choucair, Coralie Poulard, Olivier Trédan, Laura Corbo, Mona Diab-Assaf, Nader Hussein, Isabelle Treilleux, Muriel Le Romancer
Protein arginine methyltransferase 5 (PRMT5) is the main enzyme responsible for the symmetrical dimethylation of arginine residues on target proteins in both the cytoplasm and the nucleus. Though its activity has been associated with tumor progression in various cancers, the expression pattern of this oncoprotein has been scarcely studied in breast cancer. In the current work, we analyzed its expression in a large cohort of breast cancer patients, revealing higher nuclear PRMT5 levels in ERα-positive tumors and an association with prolonged disease free and overall survival...
October 5, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/30282123/genome-wide-association-study-reveals-new-loci-involved-in-arabidopsis-thaliana-and-turnip-mosaic-virus-tumv-interactions-in-the-field
#4
Bernadette Rubio, Patrick Cosson, Mélodie Caballero, Frédéric Revers, Joy Bergelson, Fabrice Roux, Valérie Schurdi-Levraud
The genetic architecture of plant response to viruses has often been studied in model non-natural pathosystems under controlled conditions. There is an urgent need to elucidate the genetic architecture of the response to viruses in a natural setting. A field experiment was performed in each of two years. In total, 318 Arabidopsis thaliana accessions were inoculated with its natural Turnip mosaic virus (TuMV). The accessions were phenotyped for viral accumulation, frequency of infected plants, stem length and symptoms...
October 3, 2018: New Phytologist
https://www.readbyqxmd.com/read/30279220/distinguishing-the-differences-in-beta-glycosylceramidase-folds-dynamics-and-actions-informs-therapeutic-uses
#5
Fredj Ben Bdira, Marta Artola, Herman S Overkleeft, Marcellus Ubbink, Johannes M Aerts
Glycosyl hydrolases (GHs) are carbohydrate-active enzymes that hydrolyze a specific β-glycosidic bond in glycoconjugate substrates; β-glucosidases degrade glucosylceramide, a ubiquitous glycosphingolipid. GHs are grouped into structurally similar families, which themselves can be grouped into clans. GH1, GH5, and GH30 glycosidases belong to clan A hydrolases with a catalytic (β/α)8 TIM barrel domain, whereas GH116 belongs to clan O with a catalytic (α/α)6 domain. In humans, GH abnormalities underlie metabolic diseases...
October 2, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/30246917/steric-hindrance-controls-pyridine-nucleotide-specificity-of-a-flavin-dependent-nadh-quinone-oxidoreductase
#6
Jacob Ball, Renata A G Reis, Johnson Agniswamy, Irene T Weber, Giovanni Gadda
The crystal structure of the NADH:quinone oxidoreductase PA1024 has been solved in complex with NAD+ to 2.2 Å resolution. The nicotinamide C4 is 3.6 Å from the FMN N5 atom, with a suitable orientation for facile hydride transfer. NAD+ binds in a folded conformation at the interface of the TIM-barrel domain and the extended domain of the enzyme. Comparison of the enzyme-NAD+ structure with that of the ligand-free enzyme revealed a different conformation of a short loop (75-86) that is part of the NAD+ -binding pocket...
September 24, 2018: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/30149704/electrostatic-potential-in-the-trna-binding-evolution-of-dihydrouridine-synthases
#7
Charles Bou-Nader, Damien Brégeon, Ludovic Pecqueur, Marc Fontecave, Djemel Hamdane
Dihydrouridine (D) is an abundant modified base of tRNA found in the majority of living organisms. This base is synthesized via an NADPH-dependent reduction of specific uridines by the dihydrouridine synthases (Dus), a large family of flavoenzymes comprising eight subfamilies. Almost all of these enzymes function with only two conserved domains, an N-terminal catalytic domain (TBD) adopting a TIM barrel fold and a unique C-terminal helical domain (HD) devoted to tRNA recognition, except for the animal U20-specific Dus2 enzyme...
September 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/30148347/search-and-subvert-minimalist-bacterial-phosphatidylinositol-specific-phospholipase-c-enzymes
#8
Mary F Roberts, Hanif M Khan, Rebecca Goldstein, Nathalie Reuter, Anne Gershenson
Phosphatidylinositol-specific phospholipase C (PI-PLC) enzymes from Gram-positive bacteria are secreted virulence factors that aid in downregulating host immunity. These PI-PLCs are minimalist peripheral membrane enzymes with a distorted (βα)8 TIM barrel fold offering a conserved and stable scaffold for the conserved catalytic amino acids while membrane recognition is achieved mostly through variable loops. Decades of experimental and computational research on these enzymes have revealed the subtle interplay between molecular mechanisms of catalysis and membrane binding, leading to a semiquantitative model for how they find, bind, and cleave their respective substrates on host cell membranes...
September 26, 2018: Chemical Reviews
https://www.readbyqxmd.com/read/30068015/-late-complications-of-permanent-intestinal-stomata
#9
Burkhard Stoffels, Nils Sommer, Christine Berteld, Tim Vilz, Martin von Websky, Jörg C Kalff, Dimitrios Pantelis
INTRODUCTION: Complications following the creation of permanent intestinal ostomies are common and lead to serious problems in the stoma care of affected patients. The aim of this prospective, single-centre follow-up study was to record the rate of late complications in our own patient group and to identify potential risk factors. METHODS: All patients who received a permanent intestinal ostomy in our clinic within the period 2006 - 2016 were included in the study...
August 1, 2018: Zentralblatt Für Chirurgie
https://www.readbyqxmd.com/read/30018322/highly-active-enzymes-by-automated-combinatorial-backbone-assembly-and-sequence-design
#10
Gideon Lapidoth, Olga Khersonsky, Rosalie Lipsh, Orly Dym, Shira Albeck, Shelly Rogotner, Sarel J Fleishman
Automated design of enzymes with wild-type-like catalytic properties has been a long-standing but elusive goal. Here, we present a general, automated method for enzyme design through combinatorial backbone assembly. Starting from a set of homologous yet structurally diverse enzyme structures, the method assembles new backbone combinations and uses Rosetta to optimize the amino acid sequence, while conserving key catalytic residues. We apply this method to two unrelated enzyme families with TIM-barrel folds, glycoside hydrolase 10 (GH10) xylanases and phosphotriesterase-like lactonases (PLLs), designing 43 and 34 proteins, respectively...
July 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29969107/crystal-structures-and-kinetic-analyses-of-n-acetylmannosamine-6-phosphate-2-epimerases-from-fusobacterium-nucleatum-and-vibrio-cholerae
#11
Lavanyaa Manjunath, Sai Rohit Guntupalli, Michael J Currie, Rachel A North, Renwick C J Dobson, Vinod Nayak, Ramaswamy Subramanian
Sialic acids are nine-carbon sugars that are found abundantly on the cell surfaces of mammals as glycoprotein or glycolipid complexes. Several Gram-negative and Gram-positive bacteria have the ability to scavenge and catabolize sialic acids to use as a carbon source. This gives them an advantage in colonizing sialic acid-rich environments. The genes of the sialic acid catabolic pathway are generally present as the operon nanAKE. The third gene in the operon encodes the enzyme N-acetylmannosamine-6-phosphate 2-epimerase (NanE), which catalyzes the conversion of N-acetylmannosamine 6-phosphate to N-acetylglucosamine 6-phosphate, thus committing it to enter glycolysis...
July 1, 2018: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/29891918/structural-basis-for-the-regulation-of-human-5-10-methylenetetrahydrofolate-reductase-by-phosphorylation-and-s-adenosylmethionine-inhibition
#12
D Sean Froese, Jolanta Kopec, Elzbieta Rembeza, Gustavo Arruda Bezerra, Anselm Erich Oberholzer, Terttu Suormala, Seraina Lutz, Rod Chalk, Oktawia Borkowska, Matthias R Baumgartner, Wyatt W Yue
The folate and methionine cycles are crucial for biosynthesis of lipids, nucleotides and proteins, and production of the methyl donor S-adenosylmethionine (SAM). 5,10-methylenetetrahydrofolate reductase (MTHFR) represents a key regulatory connection between these cycles, generating 5-methyltetrahydrofolate for initiation of the methionine cycle, and undergoing allosteric inhibition by its end product SAM. Our 2.5 Å resolution crystal structure of human MTHFR reveals a unique architecture, appending the well-conserved catalytic TIM-barrel to a eukaryote-only SAM-binding domain...
June 11, 2018: Nature Communications
https://www.readbyqxmd.com/read/29698417/the-response-to-selection-in-glycoside-hydrolase-family-13-structures-a-comparative-quantitative-genetics-approach
#13
Jose Sergio Hleap, Christian Blouin
The Glycoside Hydrolase Family 13 (GH13) is both evolutionarily diverse and relevant to many industrial applications. Its members hydrolyze starch into smaller carbohydrates and members of the family have been bioengineered to improve catalytic function under industrial environments. We introduce a framework to analyze the response to selection of GH13 protein structures given some phylogenetic and simulated dynamic information. We find that the TIM-barrel (a conserved protein fold consisting of eight α-helices and eight parallel β-strands that alternate along the peptide backbone, common to all amylases) is not selectable since it is under purifying selection...
2018: PloS One
https://www.readbyqxmd.com/read/29689137/insight-into-vitamin-b-6-dependent-epilepsy-due-to-plpbp-previously-prosc-missense-mutations
#14
Lorena Tremiño, Alicia Forcada-Nadal, Vicente Rubio
Vitamin B6 -dependent genetic epilepsy was recently associated to mutations in PLPBP (previously PROSC), the human version of the widespread COG0325 gene that encodes TIM-barrel-like pyridoxal phosphate (PLP)-containing proteins of unclear function. We produced recombinantly, purified and characterized human PROSC (called now PLPHP) and its six missense mutants reported in epileptic patients. Normal PLPHP is largely a monomer with PLP bound through a Schiff-base linkage. The PLP-targeting antibiotic d-cycloserine decreased the PLP-bound peak as expected for pseudo-first-order reaction...
July 2018: Human Mutation
https://www.readbyqxmd.com/read/29684243/biochemical-and-biophysical-studies-of-helicobacter-pylori-arginine-decarboxylase-an-enzyme-important-for-acid-adaptation-in-host
#15
Mashkoor Alam, Abhishek Srivastava, Ankita Dutta, Apurba Kumar Sau
Despite importance of arginine decarboxylase (ADC: EC 4.1.1.19) of Helicobacter pylori (H. pylori) 26695 pathogenic strain for acid adaptation in host, the enzyme has not yet been studied at a molecular level. Using combined approaches that include kinetic assays, site-directed mutagenesis, circular dichroism, heat-induced denaturation, analytical gel-filtration, and homology modeling, we report here a detailed investigation of H. pylori ADC. The pyridoxal 5'-phosphate (PLP)-dependent enzyme exhibits higher catalytic activity in the presence of Mg2+ ions at pH ∼8...
July 2018: IUBMB Life
https://www.readbyqxmd.com/read/29588661/enhancing-the-catalytic-activity-of-a-novel-gh5-cellulase-gt-cel5-from-gloeophyllum-trabeum-cbs-900-73-by-site-directed-mutagenesis-on-loop-6
#16
Fei Zheng, Tao Tu, Xiaoyu Wang, Yuan Wang, Rui Ma, Xiaoyun Su, Xiangming Xie, Bin Yao, Huiying Luo
Background: Cellulases of glycosyl hydrolase (GH) family 5 share a (β/α)8 TIM-barrel fold structure with eight βα loops surrounding the catalytic pocket. These loops exposed on the surface play a vital role in protein functions, primarily due to the interactions of some key amino acids with solvent and ligand molecules. It has been reported that motions of these loops facilitate substrate access and product release, and loops 6 and 7 located at the substrate entrance of the binding pocket promote proton transfer reaction at the catalytic site motions...
2018: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29555372/structural-and-biochemical-characterization-of-a-gh3-%C3%AE-glucosidase-from-the-probiotic-bacteria-bifidobacterium-adolescentis
#17
Renata N Florindo, Valquiria P Souza, Lívia R Manzine, Cesar M Camilo, Sandro R Marana, Igor Polikarpov, Alessandro S Nascimento
Bifidobacterium is an important genus of probiotic bacteria colonizing the human gut. These bacteria can uptake oligosaccharides for the fermentative metabolism of hexoses and pentoses, producing lactate, acetate as well as short-chain fatty acids and propionate. These end-products are known to have important effects on human health. β-glucosidases (EC 3.2.1.21) are pivotal enzymes for the metabolism and homeostasis of Bifidobacterium, since they hydrolyze small and soluble saccharides, typically producing glucose...
May 2018: Biochimie
https://www.readbyqxmd.com/read/29540555/the-abcs-of-centriole-architecture-the-form-and-function-of-triplet-microtubules
#18
Jennifer T Wang, Tim Stearns
The centriole is a defining feature of many eukaryotic cells. It nucleates a cilium, organizes microtubules as part of the centrosome, and is duplicated in coordination with the cell cycle. Centrioles have a remarkable structure, consisting of microtubules arranged in a barrel with ninefold radial symmetry. At their base, or proximal end, centrioles have unique triplet microtubules, formed from three microtubules linked to each other. This microtubule organization is not found anywhere else in the cell, is conserved in all major branches of the eukaryotic tree, and likely was present in the last eukaryotic common ancestor...
2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/29526745/integrated-models-of-neurovascular-coupling-and-bold-signals-responses-for-varying-neural-activations
#19
Elshin J Mathias, Allanah Kenny, Michael J Plank, Tim David
A state-of-the-art integrated model of neurovascular coupling (NVC) (Dormanns et al., 2015b; Dormanns et al., 2016; Kenny et al., 2018) and the BOLD response (Mathias et al., 2017a; Mathias et al., 2017b) is presented with the ability to simulate the fMRI BOLD responses due to continuous neuronal spiking, bursting and cortical spreading depression (CSD) along with the underlying complex vascular coupling. Simulated BOLD responses are compared to experimental BOLD signals observed in the rat barrel cortex and in the hippocampus under seizure conditions showing good agreement...
July 1, 2018: NeuroImage
https://www.readbyqxmd.com/read/29496453/crystal-structure-of-the-apurinic-apyrimidinic-endonuclease-iv-from-mycobacterium-tuberculosis
#20
Wei Zhang, Yueyang Xu, Mengrong Yan, Shanshan Li, Huiying Wang, Haitao Yang, Weihong Zhou, Zihe Rao
Endonuclease IV is a typical endonuclease of the apurinic-apyrimidinic (AP) or abasic endonuclease superfamily. It repairs damaged DNA through base excision repair by cleaving the DNA backbone immediately 5' of an AP site. In Mycobacterium tuberculosis, endonuclease IV is the major AP endonuclease. This enzyme is absent from mammalian cells, making it an attractive target for anti-tuberculosis drug development. In this study, the structure of the recombinant endonuclease IV from M. tuberculosis (MtbEndo IV) was determined at a high resolution of 1...
March 25, 2018: Biochemical and Biophysical Research Communications
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