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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
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...
November 5, 2016: International Journal of Medical Microbiology: IJMM
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...
October 24, 2016: Functional & Integrative Genomics
Suomeng Dong, Yuanchao Wang
[This corrects the article DOI: 10.1371/journal.ppat.1005704.].
October 2016: PLoS Pathogens
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...
September 28, 2016: Journal of Bioenergetics and Biomembranes
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
Claire Anderson, Muhammad Adil Khan, Ann-Maree Catanzariti, Cameron A Jack, Adnane Nemri, Gregory J Lawrence, Narayana M Upadhyaya, Adrienne R Hardham, Jeffrey G Ellis, Peter N Dodds, David A Jones
BACKGROUND: Rust fungi are an important group of plant pathogens that cause devastating losses in agricultural, silvicultural and natural ecosystems. Plants can be protected from rust disease by resistance genes encoding receptors that trigger a highly effective defence response upon recognition of specific pathogen avirulence proteins. Identifying avirulence genes is crucial for understanding how virulence evolves in the field. RESULTS: To facilitate avirulence gene cloning in the flax rust fungus, Melampsora lini, we constructed a high-density genetic linkage map using single nucleotide polymorphisms detected in restriction site-associated DNA sequencing (RADseq) data...
2016: BMC Genomics
Suomeng Dong, Yuanchao Wang
No abstract text is available yet for this article.
August 2016: PLoS Pathogens
Zrinka Karačić, Bojana Vukelić, Gabrielle H Ho, Iva Jozić, Iva Sučec, Branka Salopek-Sondi, Marija Kozlović, Steven E Brenner, Jutta Ludwig-Müller, Marija Abramić
In a search for plant homologues of dipeptidyl peptidase III (DPP III) family, we found a predicted protein from the moss Physcomitrella patens (UniProt entry: A9TLP4), which shared 61% sequence identity with the Arabidopsis thaliana uncharacterized protein, designated Nudix hydrolase 3. Both proteins contained all conserved regions of the DPP III family, but instead of the characteristic hexapeptide HEXXGH zinc-binding motif, they possessed a pentapeptide HEXXH, and at the N-terminus, a Nudix box, a hallmark of Nudix hydrolases, known to act upon a variety of nucleoside diphosphate derivatives...
January 1, 2017: Biological Chemistry
Katharina Höfer, Sisi Li, Florian Abele, Jens Frindert, Jasmin Schlotthauer, Julia Grawenhoff, Jiamu Du, Dinshaw J Patel, Andres Jäschke
RNA capping and decapping are thought to be distinctive features of eukaryotes. The redox cofactor NAD was recently discovered to be attached to small regulatory RNAs in bacteria in a cap-like manner, and Nudix hydrolase NudC was found to act as a NAD-decapping enzyme in vitro and in vivo. Here, crystal structures of Escherichia coli NudC in complex with substrate NAD and with cleavage product NMN reveal the catalytic residues lining the binding pocket and principles underlying molecular recognition of substrate and product...
September 2016: Nature Chemical Biology
Ewa Grudzien-Nogalska, Megerditch Kiledjian
Removal of the 5' end cap is a critical determinant controlling mRNA stability and efficient gene expression. Removal of the cap is exquisitely controlled by multiple direct and indirect regulators that influence association with the cap and the catalytic step. A subset of these factors directly stimulate activity of the decapping enzyme, while others influence remodeling of factors bound to mRNA and indirectly stimulate decapping. Furthermore, the components of the general decapping machinery can also be recruited by mRNA-specific regulatory proteins to activate decapping...
July 17, 2016: Wiley Interdisciplinary Reviews. RNA
Luca Palazzo, Casey M Daniels, Joanne E Nettleship, Nahid Rahman, Robert Lyle McPherson, Shao-En Ong, Kazuki Kato, Osamu Nureki, Anthony K L Leung, Ivan Ahel
ADP-ribosylation is a conserved post-translational protein modification that plays a role in all major cellular processes, particularly DNA repair, transcription, translation, stress response and cell death. Hence, dysregulation of ADP-ribosylation is linked to the physiopathology of several human diseases including cancers, diabetes and neurodegenerative disorders. Protein ADP-ribosylation can be reversed by the macrodomain-containing proteins PARG, TARG1, MacroD1 and MacroD2, which hydrolyse the ester bond known to link proteins to ADP-ribose as well as consecutive ADP-ribose subunits; targeting this bond can thus result in the complete removal of the protein modification or the conversion of poly(ADP-ribose) to mono(ADP-ribose)...
September 2016: FEBS Journal
Iordan Iordanov, Csaba Mihályi, Balázs Tóth, László Csanády
Transient Receptor Potential Melastatin 2 (TRPM2) is a Ca(2+)-permeable cation channel essential for immunocyte activation, insulin secretion, and postischemic cell death. TRPM2 is activated by ADP ribose (ADPR) binding to its C-terminal cytosolic NUDT9-homology (NUDT9H) domain, homologous to the soluble mitochondrial ADPR pyrophosphatase (ADPRase) NUDT9. Reported ADPR hydrolysis classified TRPM2 as a channel-enzyme, but insolubility of isolated NUDT9H hampered further investigations. Here we developed a soluble NUDT9H model using chimeric proteins built from complementary polypeptide fragments of NUDT9H and NUDT9...
2016: ELife
Frank J P Kühn, Cornelia Kühn, Mathis Winking, Daniel C Hoffmann, Andreas Lückhoff
The human redox-sensitive Transient receptor potential melastatin type 2 (hTRPM2) channel contains the C-terminal Nudix hydrolase domain NUDT9H which most likely binds ADP-ribose. During oxidative stress, the intracellular release of ADP-ribose triggers the activation of hTRPM2. The TRPM2 orthologue from Nematostella vectensis (nv) is also stimulated by ADP-ribose but not by the oxidant hydrogen peroxide. For further clarification of the structure-function relationships of these two distantly related channel orthologues, we performed whole-cell as well as single channel patch-clamp recordings, Ca2+-imaging and Western blot analysis after heterologous expression of wild-type and mutated channels in HEK-293 cells...
2016: PloS One
Takahisa Ogawa, Kohei Muramoto, Risa Takada, Shouya Nakagawa, Shigeru Shigeoka, Kazuya Yoshimura
Arabidopsis Nudix hydrolases, AtNUDX6 and 7, exhibit pyrophosphohydrolase activities toward NADH and contribute to the modulation of various defense responses, such as the poly(ADP-ribosyl)ation (PAR) reaction and salicylic acid (SA)-induced Nonexpresser of Pathogenesis-Related genes 1 (NPR1)-dependent defense pathway, against biotic and abiotic stresses. However, the mechanisms by which these enzymes regulate such cellular responses remain unclear. To clarify the functional role(s) of AtNUDX6 and 7 and NADH metabolism, we examined the effects of the transient expression of the active and inactive forms of AtNUDX6 and 7 under the control of an estrogen (ES)-inducible system on various stress responses...
June 2016: Plant & Cell Physiology
Asya Khleborodova, Xiaozhou Pan, Nagaraja N Nagre, Kevin Ryan
RNA Polymerase II transcribes beyond what later becomes the 3' end of a mature messenger RNA (mRNA). The formation of most mRNA 3' ends results from pre-mRNA cleavage followed by polyadenylation. In vitro studies have shown that low concentrations of ATP stimulate the 3' cleavage reaction while high concentrations inhibit it, but the origin of these ATP effects is unknown. ATP might enable a cleavage factor kinase or activate a cleavage factor directly. To distinguish between these possibilities, we tested several ATP structural analogs in a pre-mRNA 3' cleavage reaction reconstituted from DEAE-fractionated cleavage factors...
June 2016: Biochimie
Yoshihiko Furuike, Yuka Akita, Ikuko Miyahara, Nobuo Kamiya
Adenosine diphosphate ribose pyrophosphatase (ADPRase), a member of the Nudix family proteins, catalyzes the metal-induced and concerted general acid-base hydrolysis of ADP ribose (ADPR) into AMP and ribose-5'-phosphate (R5P). The ADPR-hydrolysis reaction of ADPRase from Thermus thermophilus HB8 (TtADPRase) requires divalent metal cations such as Mn(2+), Zn(2+), or Mg(2+) as cofactors. Here, we report the reaction pathway observed in the catalytic center of TtADPRase, based on cryo-trapping X-ray crystallography at atomic resolutions around 1...
March 29, 2016: Biochemistry
Ewa Grudzien-Nogalska, Xinfu Jiao, Man-Gen Song, Ronald P Hart, Megerditch Kiledjian
Removal of the 5'-end 7-methylguanosine cap structure is a critical step in the highly regulated process of mRNA decay. The Nudix hydrolase, Dcp2, was identified as a first decapping enzyme and subsequently shown to preferentially modulate stability of only a subset of mRNAs. This observation led to the hypothesis that mammalian cells possess multiple decapping enzymes that may function in distinct pathways. Here we report Nudt3 is a Nudix protein that possesses mRNA decapping activity in cells and is a modulator of MCF-7 breast cancer cell migration...
May 2016: RNA
Gianluca Papeo
MTH1 is a member of the nudix phosphohydrolase superfamily of enzymes, and it is involved in nucleotide pool homeostasis. The protein exerts its scavenging action by hydrolyzing oxidized nucleotides, thus avoiding their misincorporation into replicating DNA. Recent reports have validated its inhibition as a potential broad-spectrum target in oncology and have described small molecules able to engage this target with antiproliferative effect. In the accompanying paper (DOI: 10.1021/acs.jmedchem.5b01760 ), a team at AstraZeneca led by Jason G...
March 24, 2016: Journal of Medicinal Chemistry
Francisco J Corpas, Simeón Aguayo-Trinidad, Takahisa Ogawa, Kazuya Yoshimura, Shigeru Shigeoka
NADPH is an important cofactor in cell growth, proliferation and detoxification. Arabidopsis thaliana Nudix hydrolase 19 (AtNUDX19) belongs to a family of proteins defined by the conserved amino-acid sequence GX5-EX7REUXEEXGU which has the capacity to hydrolyze NADPH as a physiological substrate in vivo. Given the importance of NADPH in the cellular redox homeostasis of plants, the present study compares the responses of the main NADPH-recycling systems including NADP-isocitrate dehydrogenase (ICDH), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and NADP-malic enzyme (ME) in the leaves and roots of Arabidopsis wild-type (Wt) and knock-out (KO) AtNUDX19 mutant (Atnudx19) plants under physiological and arsenic-induced stress conditions...
March 15, 2016: Journal of Plant Physiology
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