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https://www.readbyqxmd.com/read/28705712/hydrolysis-of-diadenosine-polyphosphates-exploration-of-an-additional-role-of-mycobacterium-smegmatis-mutt1
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/28391009/the-promise-of-pharmacogenomics-in-reducing-toxicity-during-acute-lymphoblastic-leukemia-maintenance-treatment
#5
REVIEW
Shoshana Rudin, Marcus Marable, R Stephanie Huang
Pediatric acute lymphoblastic leukemia (ALL) affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenance phase, lasting 2-3years. While the primary drugs used in the maintenance phase, 6-mercaptopurine (6-MP) and methotrexate (MTX), are necessary for decreasing risk of relapse, they also have potentially serious toxicities, including myelosuppression, which may be life-threatening, and gastrointestinal toxicity...
April 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28375146/biochemical-and-structural-studies-of-mycobacterium-smegmatis-mutt1-a-sanitization-enzyme-with-unusual-modes-of-association
#6
S M Arif, A G Patil, U Varshney, M Vijayan
Mycobacterium smegmatis MutT1, which is made up of a Nudix domain (domain 1) and a histidine phosphatase domain (domain 2), efficiently hydrolyses 8-oxo-GTP and 8-oxo-dGTP to the corresponding nucleoside diphosphates and phosphate in the presence of magnesium ions. Domain 1 alone hydrolyses nucleoside triphosphates less efficiently. Under high concentrations and over long periods, the full-length enzyme as well as domain 1 catalyses the hydrolysis of the nucleoside triphosphates to the respective nucleoside monophosphates and pyrophosphate...
April 1, 2017: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/28336669/a-conserved-nad-binding-pocket-that-regulates-protein-protein-interactions-during-aging
#7
Jun Li, Michael S Bonkowski, Sébastien Moniot, Dapeng Zhang, Basil P Hubbard, Alvin J Y Ling, Luis A Rajman, Bo Qin, Zhenkun Lou, Vera Gorbunova, L Aravind, Clemens Steegborn, David A Sinclair
DNA repair is essential for life, yet its efficiency declines with age for reasons that are unclear. Numerous proteins possess Nudix homology domains (NHDs) that have no known function. We show that NHDs are NAD(+) (oxidized form of nicotinamide adenine dinucleotide) binding domains that regulate protein-protein interactions. The binding of NAD(+) to the NHD domain of DBC1 (deleted in breast cancer 1) prevents it from inhibiting PARP1 [poly(adenosine diphosphate-ribose) polymerase], a critical DNA repair protein...
March 24, 2017: Science
https://www.readbyqxmd.com/read/28302504/mitochondrial-nudix-hydrolases-a-metabolic-link-between-nad-catabolism-gtp-and-mitochondrial-dynamics
#8
Aaron Long, Nina Klimova, Tibor Kristian
NAD(+) catabolism and mitochondrial dynamics are important parts of normal mitochondrial function and are both reported to be disrupted in aging, neurodegenerative diseases, and acute brain injury. While both processes have been extensively studied there has been little reported on how the mechanisms of these two processes are linked. This review focuses on how downstream NAD(+) catabolism via NUDIX hydrolases affects mitochondrial dynamics under pathologic conditions. Additionally, several potential targets in mitochondrial dysfunction and fragmentation are discussed, including the roles of mitochondrial poly(ADP-ribose) polymerase 1(mtPARP1), AMPK, AMP, and intra-mitochondrial GTP metabolism...
March 14, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28258148/biosynthesis-of-2-chloropentostatin-and-2-amino-2-deoxyadenosine-highlights-a-single-gene-cluster-responsible-for-two-independent-pathways-in-actinomadura-sp-strain-atcc-39365
#9
Yaojie Gao, Gudan Xu, Pan Wu, Jin Liu, You-Sheng Cai, Zixin Deng, Wenqing Chen
2'-Chloropentostatin (2'-Cl PTN, 2'-chloro-2'-deoxycoformycin) and 2'-amino-2'-deoxyadenosine (2'-amino dA) are two adenosine-derived nucleoside antibiotics coproduced by Actinomadura sp. strain ATCC 39365. 2'-Cl PTN is a potent adenosine deaminase (ADA) inhibitor featuring an intriguing 1,3-diazepine ring, as well as a chlorination at C-2' of ribose, and 2'-amino dA is an adenosine analog showing bioactivity against RNA-type virus infection. However, the biosynthetic logic of them has remained poorly understood...
May 15, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28167526/vibrio-phage-kvp40-encodes-a-functional-nad-salvage-pathway
#10
Jae Yun Lee, Zhiqun Li, Eric S Miller
The genome of T4-type Vibrio bacteriophage KVP40 has five genes predicted to encode proteins of pyridine nucleotide metabolism, of which two, nadV and natV, would suffice for an NAD(+) salvage pathway. NadV is an apparent nicotinamide phosphoribosyltransferase (NAmPRTase), and NatV is an apparent bifunctional nicotinamide mononucleotide adenylyltransferase (NMNATase) and nicotinamide-adenine dinucleotide pyrophosphatase (Nudix hydrolase). Genes encoding the predicted salvage pathway were cloned and expressed in Escherichia coli, the proteins were purified, and their enzymatic properties were examined...
May 1, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28089905/nudix-type-motif-2-contributes-to-cancer-proliferation-through-the-regulation-of-rag-gtpase-mediated-mammalian-target-of-rapamycin-complex-1-localization
#11
Ohman Kwon, Dongoh Kwak, Sang Hoon Ha, Hyeona Jeon, Mangeun Park, Yeonho Chang, Pann-Ghill Suh, Sung Ho Ryu
Lysosomal localization of mammalian target of rapamycin complex 1 (mTORC1) is a critical step for activation of the molecule. Rag GTPases are essential for this translocation. Here, we demonstrate that Nudix-type motif 2 (NUDT2) is a novel positive regulator of mTORC1 activation. Activation of mTORC1 is impaired in NUDT2-silenced cells. Mechanistically, NUDT2 binds to Rag GTPase and controls mTORC1 translocation to the lysosomal membrane. Furthermore, NUDT2-dependent mTORC1 regulation is critical for proliferation of breast cancer cells, as NUDT2-silenced cells arrest in G0/G1 phases...
January 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28035004/structural-and-kinetic-studies-of-the-human-nudix-hydrolase-mth1-reveal-the-mechanism-for-its-broad-substrate-specificity
#12
Shaimaa Waz, Teruya Nakamura, Keisuke Hirata, Yukari Koga-Ogawa, Mami Chirifu, Takao Arimori, Taro Tamada, Shinji Ikemizu, Yusaku Nakabeppu, Yuriko Yamagata
The human MutT homolog 1 (hMTH1, human NUDT1) hydrolyzes oxidatively damaged nucleoside triphosphates and is the main enzyme responsible for nucleotide sanitization. hMTH1 recently has received attention as an anticancer target because hMTH1 blockade leads to accumulation of oxidized nucleotides in the cell, resulting in mutations and death of cancer cells. Unlike Escherichia coli MutT, which shows high substrate specificity for 8-oxoguanine nucleotides, hMTH1 has broad substrate specificity for oxidized nucleotides, including 8-oxo-dGTP and 2-oxo-dATP...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27974459/identification-of-the-rna-pyrophosphohydrolase-rpph-of-helicobacter-pylori-and-global-analysis-of-its-rna-targets
#13
Thorsten Bischler, Ping-Kun Hsieh, Marcus Resch, Quansheng Liu, Hock Siew Tan, Patricia L Foley, Anika Hartleib, Cynthia M Sharma, Joel G Belasco
RNA degradation is crucial for regulating gene expression in all organisms. Like the decapping of eukaryotic mRNAs, the conversion of the 5'-terminal triphosphate of bacterial transcripts to a monophosphate can trigger RNA decay by exposing the transcript to attack by 5'-monophosphate-dependent ribonucleases. In both biological realms, this deprotection step is catalyzed by members of the Nudix hydrolase family. The genome of the gastric pathogen Helicobacter pylori, a Gram-negative epsilonproteobacterium, encodes two proteins resembling Nudix enzymes...
February 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27936487/the-evolution-of-function-within-the-nudix-homology-clan
#14
John R Srouji, Anting Xu, Annsea Park, Jack F Kirsch, Steven E Brenner
The Nudix homology clan encompasses over 80,000 protein domains from all three domains of life, defined by homology to each other. Proteins with a domain from this clan fall into four general functional classes: pyrophosphohydrolases, isopentenyl diphosphate isomerases (IDIs), adenine/guanine mismatch-specific adenine glycosylases (A/G-specific adenine glycosylases), and nonenzymatic activities such as protein/protein interaction and transcriptional regulation. The largest group, pyrophosphohydrolases, encompasses more than 100 distinct hydrolase specificities...
May 2017: Proteins
https://www.readbyqxmd.com/read/27874073/loss-of-function-of-an-arabidopsis-nadph-pyrophosphohydrolase-atnudx19-impacts-on-the-pyridine-nucleotides-status-and-confers-photooxidative-stress-tolerance
#15
Takanori Maruta, Takahisa Ogawa, Masaki Tsujimura, Keisuke Ikemoto, Tomofumi Yoshida, Hiro Takahashi, Kazuya Yoshimura, Shigeru Shigeoka
The levels and redox states of pyridine nucleotides, such as NADP(H), regulate the cellular redox homeostasis, which is crucial for photooxidative stress response in plants. However, how they are controlled is poorly understood. An Arabidopsis Nudix hydrolase, AtNUDX19, was previously identified to have NADPH hydrolytic activity in vitro, suggesting this enzyme to be a regulator of the NADPH status. We herein examined the physiological role of AtNUDX19 using its loss-of-function mutants. NADPH levels were increased in nudx19 mutants under both normal and high light conditions, while NADP(+) and NAD(+) levels were decreased...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27865623/key-role-of-an-adp-ribose-dependent-transcriptional-regulator-of-nad-metabolism-for-fitness-and-virulence-of-pseudomonas-aeruginosa
#16
Elza Okon, Sarah Dethlefsen, Anna Pelnikevich, Andrea van Barneveld, Antje Munder, Burkhard Tümmler
NAD is an essential co-factor of redox reactions and metabolic conversions of NAD-dependent enzymes. NAD biosynthesis in the opportunistic pathogen Pseudomonas aeruginosa has yet not been experimentally explored. The in silico search for orthologs in the P. aeruginosa PAO1 genome identified the operon pncA - pncB1-nadE (PA4918-PA4920) to encode the nicotinamidase, nicotinate phosporibosyltransferase and Nad synthase of salvage pathway I. The functional role of the preceding genes PA4917 and PA4916 was resolved by the characterization of recombinant protein...
January 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/27778111/alr2954-of-anabaena-sp-pcc-7120-with-adp-ribose-pyrophosphatase-activity-bestows-abiotic-stress-tolerance-in-escherichia-coli
#17
Prashant Kumar Singh, Alok Kumar Shrivastava, Shilpi Singh, Ruchi Rai, Antra Chatterjee, L C Rai
In silico derived properties on experimental validation revealed that hypothetical protein Alr2954 of Anabaena sp. PCC7120 is ADP-ribose pyrophosphatase, which belongs to nudix hydrolase superfamily. Presence of ADP-ribose binding site was attested by ADP-ribose pyrophosphatase activity (K m 44.71 ± 8.043 mM, V max 7.128 ± 0.417 μmol min(-1) mg protein(-1), and K cat/K m 9.438 × 10(4) μM(-)1 min(-1)). Besides ADP-ribose, the enzyme efficiently hydrolyzed various nucleoside phosphatases such as 8-oxo-dGDP, 8-oxo-dADP, 8-oxo-dGTP, 8-oxo-dATP, GDP-mannose, ADP-glucose, and NADH...
January 2017: Functional & Integrative Genomics
https://www.readbyqxmd.com/read/27737001/correction-nudix-effectors-a-common-weapon-in-the-arsenal-of-plant-pathogens
#18
Suomeng Dong, Yuanchao Wang
[This corrects the article DOI: 10.1371/journal.ppat.1005704.].
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27683242/kinetic-and-mutational-studies-of-the-adenosine-diphosphate-ribose-hydrolase-from-mycobacterium-tuberculosis
#19
Suzanne F O'Handley, Puchong Thirawatananond, Lin-Woo Kang, Jennifer E Cunningham, J Alfonso Leyva, L Mario Amzel, Sandra B Gabelli
Mycobacterium tuberculosis represents one of the world's most devastating infectious agents - with one third of the world's population infected and 1.5 million people dying each year from this deadly pathogen. As part of an effort to identify targets for therapeutic intervention, we carried out the kinetic characterization of the product of gene rv1700 of M. tuberculosis. Based on its sequence and its structure, the protein had been tentatively identified as a pyrophosphohydrolase specific for adenosine diphosphate ribose (ADPR), a compound involved in various pathways including oxidative stress response and tellurite resistance...
December 2016: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/27618147/substrate-specificity-characterization-for-eight-putative-nudix-hydrolases-evaluation-of-criteria-for-substrate-identification-within-the-nudix-family
#20
Vi N Nguyen, Annsea Park, Anting Xu, John R Srouji, Steven E Brenner, Jack F Kirsch
The nearly 50,000 known Nudix proteins have a diverse array of functions, of which the most extensively studied is the catalyzed hydrolysis of aberrant nucleotide triphosphates. The functions of 171 Nudix proteins have been characterized to some degree, although physiological relevance of the assayed activities has not always been conclusively demonstrated. We investigated substrate specificity for eight structurally characterized Nudix proteins, whose functions were unknown. These proteins were screened for hydrolase activity against a 74-compound library of known Nudix enzyme substrates...
December 2016: Proteins
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