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https://www.readbyqxmd.com/read/29551348/biosynthesis-and-activity-of-prenylated-fmn-cofactors
#1
Po-Hsiang Wang, Anna N Khusnutdinova, Fei Luo, Johnny Xiao, Kayla Nemr, Robert Flick, Greg Brown, Radhakrishnan Mahadevan, Elizabeth A Edwards, Alexander F Yakunin
Prenylated flavin mononucleotide (prFMN) is a recently discovered cofactor required by the UbiD family of reversible decarboxylases involved in ubiquinone biosynthesis, biological decomposition of lignin, and biotransformation of aromatic compounds. This cofactor is synthesized by UbiX-like prenyltransferases catalyzing the transfer of the dimethylallyl moiety of dimethylallyl-monophosphate (DMAP) to FMN. The origin of DMAP for prFMN biosynthesis and the biochemical properties of free prFMN are unknown. We show that in Escherichia coli cells, DMAP can be produced by phosphorylating prenol using ThiM or dephosphorylating DMAPP using Nudix hydrolases...
May 17, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29550664/linalool-and-linalool-nerolidol-synthases-in-roses-several-genes-for-little-scent
#2
Jean-Louis Magnard, Aurélie Rius Bony, Fabienne Bettini, Ausilia Campanaro, Bernard Blerot, Sylvie Baudino, Frédéric Jullien
Roses are widely appreciated for the appearance of their flowers and for their fragrance. This latter character results from the combination of different odorant molecules among which monoterpenes are often prevalent constituents. In this study, we report the cloning and characterization of three rose monoterpene synthases. In vitro functional characterization of these enzymes showed that one is a (-)-(3R)-linalool synthase whereas the others have a dual (+)-(3S)-linalool nerolidol synthase activity. However, given that the characterized rose cultivars were only able to produce the (-)-(3R)-linalool stereoisomer, the linalool nerolidol synthases are probably not active in planta...
June 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29483298/hydrolytic-activity-of-human-nudt16-enzyme-on-dinucleotide-cap-analogs-and-short-capped-oligonucleotides
#3
Renata Grzela, Karolina Nasilowska, Maciej Lukaszewicz, Michal Tyras, Janusz Stepinski, Marzena Jankowska-Anyszka, Elzbieta Bojarska, Edward Darzynkiewicz
Human Nudt16 (hNudt16) is a member of the Nudix family of hydrolases, comprising enzymes catabolizing various substrates including canonical (d)NTPs, oxidized (d)NTPs, nonnucleoside polyphosphates, and capped mRNAs. Decapping activity of the Xenopus laevis (X29) Nudt16 homolog was observed in the nucleolus, with a high specificity toward U8 snoRNA. Subsequent studies have reported cytoplasmic localization of mammalian Nudt16 with cap hydrolysis activity initiating RNA turnover, similar to Dcp2. The present study focuses on hNudt16 and its hydrolytic activity toward dinucleotide cap analogs and short capped oligonucleotides...
May 2018: RNA
https://www.readbyqxmd.com/read/29413322/human-nudt22-is-a-udp-glucose-galactose-hydrolase-exhibiting-a-unique-structural-fold
#4
Megan Carter, Ann-Sofie Jemth, Jordi Carreras-Puigvert, Patrick Herr, Markel Martínez Carranza, Karl S A Vallin, Adam Throup, Thomas Helleday, Pål Stenmark
Human NUDT22 belongs to the diverse NUDIX family of proteins, but has, until now, remained uncharacterized. Here we show that human NUDT22 is a Mg2+ -dependent UDP-glucose and UDP-galactose hydrolase, producing UMP and glucose 1-phosphate or galactose 1-phosphate. We present the structure of human NUDT22 alone and in a complex with the substrate UDP-glucose. These structures reveal a partially conserved NUDIX fold domain preceded by a unique N-terminal domain responsible for UDP moiety binding and recognition...
February 6, 2018: Structure
https://www.readbyqxmd.com/read/29378847/nudt19-is-a-renal-coa-diphosphohydrolase-with-biochemical-and-regulatory-properties-that-are-distinct-from-the-hepatic-nudt7-isoform
#5
Stephanie A Shumar, Evan W Kerr, Werner J Geldenhuys, Grace E Montgomery, Paolo Fagone, Puchong Thirawatananond, Harry Saavedra, Sandra B Gabelli, Roberta Leonardi
CoA is the major acyl carrier in mammals and a key cofactor in energy metabolism. Dynamic regulation of CoA in different tissues and organs supports metabolic flexibility. Two mammalian Nudix hydrolases, Nudt19 and Nudt7, degrade CoA in vitro Nudt19 and Nudt7 possess conserved Nudix and CoA signature sequences and specifically hydrolyze the diphosphate bond of free CoA and acyl-CoAs to form 3',5'-ADP and 4'-(acyl)phosphopantetheine. Limited information is available on these enzymes, but the relatively high abundance of Nudt19 and Nudt7 mRNA in the kidney and liver, respectively, suggests that they play specific roles in the regulation of CoA levels in these organs...
March 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29367493/substrate-specificity-of-nudix-hydrolases-from-myxococcus-xanthus
#6
Yoshio Kimura, Yuuka Yamamoto, Sayaka Kajimoto, Ai Sakai, Kaoru Takegawa
No abstract text is available yet for this article.
January 25, 2018: Journal of General and Applied Microbiology
https://www.readbyqxmd.com/read/29343827/targeted-nudt5-inhibitors-block-hormone-signaling-in-breast-cancer-cells
#7
Brent D G Page, Nicholas C K Valerie, Roni H G Wright, Olov Wallner, Rebecka Isaksson, Megan Carter, Sean G Rudd, Olga Loseva, Ann-Sofie Jemth, Ingrid Almlöf, Jofre Font-Mateu, Sabin Llona-Minguez, Pawel Baranczewski, Fredrik Jeppsson, Evert Homan, Helena Almqvist, Hanna Axelsson, Shruti Regmi, Anna-Lena Gustavsson, Thomas Lundbäck, Martin Scobie, Kia Strömberg, Pål Stenmark, Miguel Beato, Thomas Helleday
With a diverse network of substrates, NUDIX hydrolases have emerged as a key family of nucleotide-metabolizing enzymes. NUDT5 (also called NUDIX5) has been implicated in ADP-ribose and 8-oxo-guanine metabolism and was recently identified as a rheostat of hormone-dependent gene regulation and proliferation in breast cancer cells. Here, we further elucidate the physiological relevance of known NUDT5 substrates and underscore the biological requirement for NUDT5 in gene regulation and proliferation of breast cancer cells...
January 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29327656/nad-nadh-homeostasis-affects-metabolic-adaptation-to-hypoxia-and-secondary-metabolite-production-in-filamentous-fungi
#8
Motoyuki Shimizu
Filamentous fungi are used to produce fermented foods, organic acids, beneficial secondary metabolites and various enzymes. During such processes, these fungi balance cellular NAD+ :NADH ratios to adapt to environmental redox stimuli. Cellular NAD(H) status in fungal cells is a trigger of changes in metabolic pathways including those of glycolysis, fermentation, and the production of organic acids, amino acids and secondary metabolites. Under hypoxic conditions, high NADH:NAD+ ratios lead to the inactivation of various dehydrogenases, and the metabolic flow involving NAD+ is down-regulated compared with normoxic conditions...
February 2018: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29142246/a-comprehensive-structural-biochemical-and-biological-profiling-of-the-human-nudix-hydrolase-family
#9
Jordi Carreras-Puigvert, Marinka Zitnik, Ann-Sofie Jemth, Megan Carter, Judith E Unterlass, Björn Hallström, Olga Loseva, Zhir Karem, José Manuel Calderón-Montaño, Cecilia Lindskog, Per-Henrik Edqvist, Damian J Matuszewski, Hammou Ait Blal, Ronnie P A Berntsson, Maria Häggblad, Ulf Martens, Matthew Studham, Bo Lundgren, Carolina Wählby, Erik L L Sonnhammer, Emma Lundberg, Pål Stenmark, Blaz Zupan, Thomas Helleday
The NUDIX enzymes are involved in cellular metabolism and homeostasis, as well as mRNA processing. Although highly conserved throughout all organisms, their biological roles and biochemical redundancies remain largely unclear. To address this, we globally resolve their individual properties and inter-relationships. We purify 18 of the human NUDIX proteins and screen 52 substrates, providing a substrate redundancy map. Using crystal structures, we generate sequence alignment analyses revealing four major structural classes...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29113256/nudt-expression-is-predictive-of-prognosis-in-patients-with-clear-cell-renal-cell-carcinoma
#10
Yue Wang, Fangning Wan, Kun Chang, Xiaolin Lu, Bo Dai, Dingwei Ye
The nudix hydroxylase (NUDT) family of genes may have notable roles in cancer growth and metastasis. The present study aimed to determine the prognostic ability of NUDT genes in clear cell renal cell carcinoma (ccRCC). Data from 509 patients with ccRCC was obtained from The Cancer Genome Atlas (TCGA) database and 192 patient samples from Fudan University Shanghai Cancer Center (FUSCC) were analyzed in the present study. The expression profile of NUDT gene family members in the TCGA cohort was obtained from the TCGA RNA sequencing database...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29065511/novel-tetra-primer-arms-pcr-assays-for-thiopurine-intolerance-susceptibility-mutations-nudt15-c-415c-t-and-tpmt-c-719a-g-tpmt-3c-in-east-asians
#11
Chi-Chun Ho, Wai-Ying Fong, Yuen-Hon Lee, Wing-Tat Poon
Thiopurines are clinically useful in the management of diverse immunological and malignant conditions. Nevertheless, these purine analogues can cause lethal myelosuppression, which may be prevented by prospective testing for variants in the thiopurine S-methyltransferase ( TPMT ) and, in East Asians, Nudix hydrolase 15 ( NUDT15 ) genes. Two single-tube, tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR) assays were developed to genotype the common loss-of-function variants NUDT15 c...
October 23, 2017: Genes
https://www.readbyqxmd.com/read/29021398/characterization-of-the-african-swine-fever-virus-decapping-enzyme-during-infection
#12
Ana Quintas, Daniel Pérez-Núñez, Elena G Sánchez, Maria L Nogal, Matthias W Hentze, Alfredo Castelló, Yolanda Revilla
African swine fever virus (ASFV) infection is characterized by a progressive decrease in cellular protein synthesis with a concomitant increase in viral protein synthesis, though the mechanism by which the virus achieves this is still unknown. Decrease of cellular mRNA is observed during ASFV infection, suggesting that inhibition of cellular proteins is due to an active mRNA degradation process. ASFV carries a gene (Ba71V D250R/Malawi g5R) that encodes a decapping protein (ASFV-DP) that has a Nudix hydrolase motif and decapping activity in vitro Here, we show that ASFV-DP was expressed from early times and accumulated throughout the infection with a subcellular localization typical of the endoplasmic reticulum, colocalizing with the cap structure and interacting with the ribosomal protein L23a...
December 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28960137/galleria-mellonella-as-an-infection-model-to-investigate-virulence-of-vibrio-parahaemolyticus
#13
Sariqa Wagley, Richard Borne, Jamie Harrison, Craig Baker-Austin, Donatella Ottaviani, Francesca Leoni, Varaporn Vuddhakul, Richard W Titball
Non-toxigenic V. parahaemolyticus isolates (tdh- /trh- /T3SS2- ) have recently been isolated from patients with gastroenteritis. In this study we report that the larvae of the wax moth (Galleria mellonella) are susceptible to infection by toxigenic or non-toxigenic clinical isolates of V. parahaemolyticus. In comparison larvae inoculated with environmental isolates of V. parahaemolyticus did not succumb to disease. Whole genome sequencing of clinical non-toxigenic isolates revealed the presence of a gene encoding a nudix hydrolase, identified as mutT...
January 1, 2018: Virulence
https://www.readbyqxmd.com/read/28833678/nudix-type-rna-pyrophosphohydrolase-provides-homeostasis-of-virulence-factor-pyocyanin-and-functions-as-a-global-regulator-in-pseudomonas-aeruginosa
#14
Martyna Kujawa, Maciej Lirski, Mateusz Ziecina, Joanna Drabinska, Marta Modzelan, Elzbieta Kraszewska
The PA0336 protein from Pseudomonas aeruginosa belongs to the family of widely distributed Nudix pyrophosphohydrolases, which catalyze the hydrolysis of pyrophosphate bonds in a variety of nucleoside diphosphate derivatives. The amino acid sequence of the PA0336 protein is highly similar to that of the RppH Nudix RNA pyrophosphohydrolase from Escherichia coli, which removes pyrophosphate from 5'-end of triphosphorylated RNA transcripts. Trans-complementation experiments showed that the P. aeruginosa enzyme can functionally substitute for RppH in E...
November 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28755312/mouse-nudt13-is-a-mitochondrial-nudix-hydrolase-with-nad-p-h-pyrophosphohydrolase-activity
#15
Salama R Abdelraheim, David G Spiller, Alexander G McLennan
The mammalian NUDT13 protein possesses a sequence motif characteristic of the NADH pyrophosphohydrolase subfamily of Nudix hydrolases. Due to the persistent insolubility of the recombinant product expressed in Escherichia coli, active mouse Nudt13 was expressed in insect cells from a baculovirus vector as a histidine-tagged recombinant protein. In vitro, it efficiently hydrolysed NADH to NMNH and AMP and NADPH to NMNH and 2',5'-ADP and had a marked preference for the reduced pyridine nucleotides. Much lower activity was obtained with other nucleotide substrates tested...
October 2017: Protein Journal
https://www.readbyqxmd.com/read/28742822/metal-ion-coordination-in-the-e-coli-nudix-hydrolase-dihydroneopterin-triphosphate-pyrophosphatase-new-clues-into-catalytic-mechanism
#16
Shannon E Hill, Elaine Nguyen, Chiamaka U Ukachukwu, Dana M Freeman, Stephen Quirk, Raquel L Lieberman
Dihydroneopterin triphosphate pyrophosphatase (DHNTPase), a member of the Mg2+ dependent Nudix hydrolase superfamily, is the recently-discovered enzyme that functions in the second step of the pterin branch of the folate biosynthetic pathway in E. coli. DHNTPase is of interest because inhibition of enzymes in bacterial folate biosynthetic pathways is a strategy for antibiotic development. We determined crystal structures of DHNTPase with and without activating, Mg2+-mimicking metals Co2+ and Ni2+. Four metal ions, identified by anomalous scattering, and stoichiometrically confirmed in solution by isothermal titration calorimetry, are held in place by Glu56 and Glu60 within the Nudix sequence motif, Glu117, waters, and a sulfate ion, of which the latter is further stabilized by a salt bridge with Lys7...
2017: PloS One
https://www.readbyqxmd.com/read/28705712/hydrolysis-of-diadenosine-polyphosphates-exploration-of-an-additional-role-of-mycobacterium-smegmatis-mutt1
#17
S M Arif, U Varshney, M Vijayan
Diadenosine polyphosphates (ApnA, n=2-6), particularly Ap4A, are involved in several important physiological processes. The substantial sequence identity of the Nudix hydrolase domain (domain 1) of Mycobacterium smegmatis MutT1 (MsMutT1) with a known Ap4A hydrolase suggested that MsMutT1 could also hydrolyse diadenosine polyphosphates. Biochemical experiments yielded results in conformity with this suggestion, with Ap4A as the best among the substrates. ATP is a product in all experiments; small amounts of ADP were also observed in the experiments involving Ap4A and Ap6A...
July 10, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28628654/the-apah-like-phosphatase-tbalph1-is-the-major-mrna-decapping-enzyme-of-trypanosomes
#18
Susanne Kramer
5'-3' decay is the major mRNA decay pathway in many eukaryotes, including trypanosomes. After deadenylation, mRNAs are decapped by the nudix hydrolase DCP2 of the decapping complex and finally degraded by the 5'-3' exoribonuclease. Uniquely, trypanosomes lack homologues to all subunits of the decapping complex, while deadenylation and 5'-3' degradation are conserved. Here, I show that the parasites use an ApaH-like phosphatase (ALPH1) as their major mRNA decapping enzyme. The protein was recently identified as a novel trypanosome stress granule protein and as involved in mRNA binding...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28559906/drawing-links-from-transcriptome-to-metabolites-the-evolution-of-aroma-in-the-ripening-berry-of-moscato-bianco-vitis-vinifera-l
#19
Laura Costantini, Christian D Kappel, Massimiliano Trenti, Juri Battilana, Francesco Emanuelli, Maddalena Sordo, Marco Moretto, Céline Camps, Roberto Larcher, Serge Delrot, Maria S Grando
Monoterpenes confer typical floral notes to "Muscat" grapevine varieties and, to a lesser extent, to other aromatic non-Muscat varieties. Previous studies have led to the identification and functional characterization of some enzymes and genes in this pathway. However, the underlying genetic map is still far from being complete. For example, the specific steps of monoterpene metabolism and its regulation are largely unknown. With the aim of identifying new candidates for the missing links, we applied an integrative functional genomics approach based on the targeted metabolic and genome-wide transcript profiling of Moscato Bianco ripening berries...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28498350/comparison-of-direct-sequencing-real-time-pcr-high-resolution-melt-pcr-hrm-and-pcr-restriction-fragment-length-polymorphism-pcr-rflp-analysis-for-genotyping-of-common-thiopurine-intolerant-variant-alleles-nudt15-c-415c-t-and-tpmt-c-719a-g-tpmt-3c
#20
Wai-Ying Fong, Chi-Chun Ho, Wing-Tat Poon
Thiopurine intolerance and treatment-related toxicity, such as fatal myelosuppression, is related to non-function genetic variants encoding thiopurine S-methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15). Genetic testing of the common variants NUDT15:NM_018283.2:c.415C>T (Arg139Cys, dbSNP rs116855232 T allele) and TPMT: NM_000367.4:c.719A>G (TPMT*3C, dbSNP rs1142345 G allele) in East Asians including Chinese can potentially prevent treatment-related complications. Two complementary genotyping approaches, real-time PCR-high resolution melt (PCR-HRM) and PCR-restriction fragment length morphism (PCR-RFLP) analysis were evaluated using conventional PCR and Sanger sequencing genotyping as the gold standard...
May 12, 2017: Diagnostics
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