Cloning, expression and characterization of YSA1H, a human adenosine 5′-diphosphosugar pyrophosphatase possessing a MutT motif

Gasmi, Lakhdar; Cartwright, Jared; McLennan, Alexander G.

doi:10.1042/bj3440331

Cited by 42 publications

(27 citation statements)

References 28 publications

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“…In terms of apparent K m , the affinity of AGPPase for NAD ϩ , ADPribose, UDPG, and CDPglucose is about 4-to 5-fold lower than that for ADPG. In contrast to the case of nucleoside diphosphate sugar pyrophosphatases occurring in animals, yeast, and bacteria (16)(17)(18)(19)(20)(21), AGPPase exhibits a high affinity to the synthetic substrate bis-PNPP, which is a reagent commonly used to measure phosphodiesterase activities (10).…”

Section: Verification Of Reaction Products and Enzyme Designationmentioning

confidence: 99%

“…Remarkably, the enzyme is not affected by typical phosphodiesterase and nucleoside diphosphate sugar pyrophosphatase effectors such as metal ions, fluoride, metal-binding reagents, sulfhydrylgroup reacting agents, and reducing compounds (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Also, in clear contrast to phosphodiesterases and nucleotide sugar hydrolases having basic optimum pH (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26), AGPPase shows a sharp pH-activity profile with optimal activity occurring at pH 6.0, which dramatically decreases at basic pH values (Fig. 1).…”

Section: Verification Of Reaction Products and Enzyme Designationmentioning

confidence: 99%

“…Because of the similarity of this reaction with that of nucleoside diphosphate sugar pyrophosphatases (EC 3.6.1.13 and EC 3.6.1.21) occurring in mammalian tissues (16,17), bacteria (18,19), and yeast (20,21), we have designated the enzyme responsible for the hydrolytic cleavage of ADPG as AGPPase.…”

Section: Verification Of Reaction Products and Enzyme Designationmentioning

confidence: 99%

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Adenosine diphosphate glucose pyrophosphatase: A plastidial phosphodiesterase that prevents starch biosynthesis

Rodrı́guez-López

Baroja‐Fernández

Zandueta-Criado

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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A distinct phosphodiesterasic activity (EC 3.1.4) was found in both mono-and dicotyledonous plants that catalyzes the hydrolytic breakdown of ADPglucose (ADPG) to produce equimolar amounts of glucose-1-phosphate and AMP. The enzyme responsible for this activity, referred to as ADPG pyrophosphatase (AGPPase), was purified over 1,100-fold from barley leaves and subjected to biochemical characterization. The calculated K eq (modified equilibrium constant) value for the ADPG hydrolytic reaction at pH 7.0 and 25°C is 110, and its standard-state free-energy change value (⌬G) is ؊2.9 kcal͞mol (1 kcal ‫؍‬ 4.18 kJ). Kinetic analyses showed that, although AGPPase can hydrolyze several low-molecular weight phosphodiester bond-containing compounds, ADPG proved to be the best substrate (K m ‫؍‬ 0.5 mM). Pi and phosphorylated compounds such as 3-phosphoglycerate, PP i, ATP, ADP, NADP ؉ , and AMP are inhibitors of AGPPase. Subcellular localization studies revealed that AGPPase is localized exclusively in the plastidial compartment of cultured cells of sycamore (Acer pseudoplatanus L.), whereas it occurs both inside and outside the plastid in barley endosperm. In this paper, evidence is presented that shows that AGPPase, whose activity declines concomitantly with the accumulation of starch during development of sink organs, competes with starch synthase (ADPG:1,4-␣-D-glucan 4-␣-D-glucosyltransferase; EC 2.4.1.21) for ADPG, thus markedly blocking the starch biosynthesis.A lthough the pyrophosphorolytic reactions leading to the production of gluconeogenic intermediates such as ADPglucose (ADPG) and UDPglucose (UDPG) are readily reversible, they mainly proceed toward the direction of nucleotide sugar synthesis (1). On the other hand, plant enzymes that irreversibly cleave nucleotide sugars have been described that may effectively interrupt the flow of glycosyl moieties toward the biosynthesis of end products such as starch, cell wall polysaccharides, or sucrose (2). It is conceivable that in conjunction with ADPG pyrophosphorylase (AGPase; EC 2.7.7.27), UDPG pyrophosphorylase, sucrose synthase, and starch synthase, among others, these enzymes will participate in controlling the levels of nucleotide sugars engaged in starch formation. Among a few enzymes reported to date that can hydrolyze nucleotide sugars in plants, ADPG phosphorylase is shown to catalyze the phosphorolytic breakdown of ADPG (3). UDPG phosphorylase is known to split UDPG in the presence of P i , and its activities are greatly stimulated by some signal metabolites, indicating that it may play an important role in the control of photosynthate partitioning (4).Based on experimental grounds, Pozueta-Romero et al. (5) have proposed the operation of synthesis͞breakdown metabolic cycles controlling the rate of starch formation. According to this hypothesis, the balance between enzymatic activities catalyzing the synthesis of gluconeogenic intermediates and those activities catalyzing their breakdown can determine the net rate of starch synthesis. Because of the possibil...

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Section: Verification Of Reaction Products and Enzyme Designationmentioning

confidence: 99%

Section: Verification Of Reaction Products and Enzyme Designationmentioning

confidence: 99%

Section: Verification Of Reaction Products and Enzyme Designationmentioning

confidence: 99%

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Adenosine diphosphate glucose pyrophosphatase: A plastidial phosphodiesterase that prevents starch biosynthesis

Rodrı́guez-López

Baroja‐Fernández

Zandueta-Criado

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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“…NUDT5 may also prevent transcriptional errors and mistranslation. Prior studies (19)(20)(21) also found that lowered NUDT5 expression led to cell cycle inhibition in HeLa cells (21). Further studies indicated that the NUDT5 protein may have notable roles in regulating the G1-S transition in mammalian cells (22)(23)(24).…”

Section: Nudt5 Nudt9p1 Nudt16 Nudt17 --------------------------------mentioning

confidence: 99%

“…ADP Ribose is a member of a family of proteins involved in a number of cellular processes such as DNA repair, genomic stability and programmed cell death (19,20). In experiments in vitro, NUDT5 suppressed the increased mutation rate of cancer cells and may act in concert with NUDT1 or NUDT15 in antimutagenesis (19,20).…”

Section: Nudt5 Nudt9p1 Nudt16 Nudt17 --------------------------------mentioning

confidence: 99%

NUDT expression is predictive of prognosis in patients with clear cell renal cell carcinoma

et al. 2017

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Abstract. 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. Pathological characteristics, including age, sex, tumor size, tumor grade, stage, laterality and overall survival were collected. Cox proportional hazards regression model and Kaplan-Meier survival analysis were performed to assess the associations between pathological characteristics and expression levels of NUDT family genes. NUDT family genes that exhibited associations with overall survival (OS) were further validated in the FUSCC cohort. In the TCGA cohort, Cox proportional hazards analysis found that NUDT5 [hazards ratio (HR)=1.676; 95% confidence interval (CI), 1.097-2.559] and NUDT17 (HR=1.375; 95% CI, 1.092-1.732) were predictive of ccRCC prognosis. Further analysis revealed that low NUDT5 (P<0.0001) and NUDT17 (P<0.0001) expression were associated with poorer OS rates in the TCGA cohort. In the FUSCC cohort, low NUDT5 expression was also associated with poor OS rates (P=0.0116), and tumor grade was a factor that influenced the expression level of NUDT5 (P=0.016).

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The evolution of function within the Nudix homology clan

Srouji

Park

et al. 2017

Proteins

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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 non-enzymatic activities such as protein/protein interaction and transcriptional regulation. The largest group, pyrophosphohydrolases, encompasses more than 100 distinct hydrolase specificities. To understand the evolution of this vast number of activities, we assembled and analyzed experimental and structural data for 205 Nudix proteins collected from the literature. We corrected erroneous functions or provided more appropriate descriptions for 53 annotations described in the Gene Ontology Annotation database in this family, and propose 275 new experimentally-based annotations. We manually constructed a structure-guided sequence alignment of 78 Nudix proteins. Using the structural alignment as a seed, we then made an alignment of 347 “select” Nudix homology domains, curated from structurally determined, functionally characterized, or phylogenetically important Nudix domains. Based on our review of Nudix pyrophosphohydrolase structures and specificities, we further analyzed a loop region downstream of the Nudix hydrolase motif previously shown to contact the substrate molecule and possess known functional motifs. This loop region provides a potential structural basis for the functional radiation and evolution of substrate specificity within the hydrolase family. Finally, phylogenetic analyses of the 347 select protein domains and of the complete Nudix homology clan revealed general monophyly with regard to function and a few instances of probable homoplasy.

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Cloning, expression and characterization of YSA1H, a human adenosine 5′-diphosphosugar pyrophosphatase possessing a MutT motif

Cited by 42 publications

References 28 publications

Adenosine diphosphate glucose pyrophosphatase: A plastidial phosphodiesterase that prevents starch biosynthesis

Adenosine diphosphate glucose pyrophosphatase: A plastidial phosphodiesterase that prevents starch biosynthesis

NUDT expression is predictive of prognosis in patients with clear cell renal cell carcinoma

The evolution of function within the Nudix homology clan

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