A Common Mutation in Paraoxonase-2 Results in Impaired Lactonase Activity

Stoltz, David A.; Ozer, Egon A.; Recker, Thomas J.; Estin, Miriam; Yang, Xia; Shih, Diana M.; Lusis, Aldons J.; Zabner, Joseph

doi:10.1074/jbc.m109.051706

Cited by 55 publications

(63 citation statements)

References 37 publications

(41 reference statements)

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“…In contrast, PON2-N254A or -N323A migrated between glycosylated and deglycosylated PON2-WT, and double mutant N254A/N323A was identical to deglycosylated PON2-WT. Thus, PON2 is glycosylated on both Asn 254 and Asn 323 , which is consistent with Stoltz et al (30).…”

Section: Pon2 Has Independentsupporting

confidence: 80%

“…disturbed initial folding due to lacking glycosylation, we also analyzed lysates with prior deglycosylation, upon which active PON2-WT again lost activity (not shown). In contrast to Stoltz et al (30), however, we did not observe any impact of natural polymorphism Ser/Cys 311 on 3OC12 hydrolysis (Fig. 3B).…”

Section: Pon2 Has Independentcontrasting

confidence: 56%

“…Further, the role of the polymorphism Ser/Cys 311 of PON2 remains controversial. Recently, Stoltz et al (30) claimed that Cys 311 impaired PON2 activity, but we did not observe this effect. One putative confounder may come from technical differences (we measured 3OC12 hydrolysis directly, whereas Stoltz et al (30) employed a Bio-assay).…”

Section: Discussioncontrasting

confidence: 43%

“…Recently, Stoltz et al (30) claimed that Cys 311 impaired PON2 activity, but we did not observe this effect. One putative confounder may come from technical differences (we measured 3OC12 hydrolysis directly, whereas Stoltz et al (30) employed a Bio-assay). Also, we measured initial rates at a 3OC12 concentration of 50 M, whereas Stoltz et al (30) used 10 M 3OC12 and did not measure initial rates.…”

Section: Discussioncontrasting

confidence: 43%

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One Enzyme, Two Functions

Altenhöfer

Witte

Teiber

et al. 2010

Journal of Biological Chemistry

137

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The human enzyme paraoxonase-2 (PON2) has two functions, an enzymatic lactonase activity and the reduction of intracellular oxidative stress. As a lactonase, it dominantly hydrolyzes bacterial signaling molecule 3OC12 and may contribute to the defense against pathogenic Pseudomonas aeruginosa. By its anti-oxidative effect, PON2 reduces cellular oxidative damage and influences redox signaling, which promotes cell survival. This may be appreciated but also deleterious given that high PON2 levels reduce atherosclerosis but may stabilize tumor cells. Here we addressed the unknown mechanisms and linkage of PON2 enzymatic and anti-oxidative function. We demonstrate that PON2 indirectly but specifically reduced superoxide release from the inner mitochondrial membrane, irrespective whether resulting from complex I or complex III of the electron transport chain. , was critical to its activity. Importantly, none of these mutations altered the anti-oxidative/anti-apoptotic function of PON2, demonstrating unrelated activities of the same protein. Collectively, our study provides detailed mechanistic insight into the functions of PON2, which is important for its role in innate immunity, atherosclerosis, and cancer.

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Section: Pon2 Has Independentsupporting

confidence: 80%

Section: Pon2 Has Independentcontrasting

confidence: 56%

Section: Discussioncontrasting

confidence: 43%

Section: Discussioncontrasting

confidence: 43%

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One Enzyme, Two Functions

Altenhöfer

Witte

Teiber

et al. 2010

Journal of Biological Chemistry

137

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“…Sabe-se que a substituição de uma Cisteína (C) por uma Serina (S), na posição 311, altera a glicosilação da enzima e diminui a atividade lactonase exercida pela mesma (Stoltz et al, 2009).…”

Section: Polimorfismos Genéticos Na Pon2unclassified

Estudo das paraoxonases 1, 2 e 3 em pacientes portadores de anemia falciforme"

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Enzymatic detoxification: a sustainable means of degrading toxic organophosphate pesticides and chemical warfare nerve agents

Manco

Porzio

Suzumoto

2018

J of Chemical Tech & Biotech

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Organophosphorus (OP) compounds are highly toxic molecules mainly used as pesticides. OP compounds also include nerve gases used in the past as chemical warfare agents and collectively OP pesticides and nerve gases are referred to as nerve agents (NA). An intensive, widespread use of pesticides since the 20th century has resulted in the emergence of an urgent global issue concerning both environment and human health. In addition, past terroristic acts and the recent dramatic events in Syria highlighted more than ever the need to explore applicable strategies for the sensing, decontamination and detoxification of these compounds in stored bulks, on critical surfaces and media (food, water and air) and for in vivo prophylaxes and therapies.OP compounds, act as covalent inhibitors of acetylcholinesterase (AChE) in the nerve system of vertebrates, thus posing a substantial threat to the ecosystem. In order to address a strong demand for the establishment of an environmental monitoring system and remediation process for NA, an increasing number of studies have been focused on the enzymatic degradation in vitro. Use of enzymes for detoxification and decontamination of toxic NA could provide a long‐term benefit as it is environmentally friendly compared with conventional methods such as chemical treatments and incineration. This review presents an overview of the current state of enzymatic detoxification research against NA. This includes the detailed characterization and protein engineering for the improvement in NA‐degrading activities of such enzymes. Research on biosensors for NA detection and identification, although important in the field, has not been treated in this review. Instead special attention has been paid to the Phosphotriesterase‐Like‐Lactonase (PLL) enzyme family. Several PLL enzymes have been isolated from hyperthermophilic Archaea or thermophilic/extremophilic Bacteria, and exhibit exceptional thermal stability. Extremophilic PLLs therefore hold promise for potential industrial application towards NA detoxification. © 2018 Society of Chemical Industry

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A Common Mutation in Paraoxonase-2 Results in Impaired Lactonase Activity

Cited by 55 publications

References 37 publications

One Enzyme, Two Functions

One Enzyme, Two Functions

Estudo das paraoxonases 1, 2 e 3 em pacientes portadores de anemia falciforme"

Enzymatic detoxification: a sustainable means of degrading toxic organophosphate pesticides and chemical warfare nerve agents

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