Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new membrane-associated 2,4,6-trichlorophenol reductive dehalogenase from Desulfitobacterium frappieri PCP-1 was isolated. Initial characterization of the crude preparation showed that the dechlorinating activity was sensitive to oxygen, and its optimum pH was 7.0. Its dechlorinating activity was not inhibited by sulphate, was completely inhibited by 1 mM sulphite, and partially inhibited by 5 mM sodium azide and by more than 5 mM nitrate. Several polychlorophenols were dechlorinated in the ortho position with respect to the hydroxy group. A dehalogenase was purified to apparent homogeneity. SDS gel electrophoresis revealed a single protein band with a molecular mass of 37 kDa. However, after two-dimensional gel electrophoresis, this band was composed of three isoforms. MS analyses showed that the three isoforms were from the same protein and the molecular mass of the most abundant isoform is 33800 Da. A mixture of iodopropane and titanium citrate caused a light-reversible inhibition of the dechlorinating activity, suggesting the involvement of a corrinoid cofactor. The apparent K(m) value for 2,4,6-trichlorophenol and pentachlorophenol were 18.3+/-2.8 microM and 26.8+/-2.9 microM respectively, at a methyl viologen concentration of 2 mM. The N-terminal amino acid sequence and an internal tryptic peptide sequence were determined. One open reading frame (ORF) was found in the Desulfitobacterium hafniense genome containing these peptides sequences. The corresponding ORF in D. frappieri PCP-1 was cloned and sequenced. This ORF, that we designated crdA, showed no homology with any known dehalogenase, suggesting a distinct reductive dehalogenase.
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PMID:Purification, cloning and sequencing of an enzyme mediating the reductive dechlorination of 2,4,6-trichlorophenol from Desulfitobacterium frappieri PCP-1. 1269 29

Semistatic acute toxicity tests of amphibian larvae (Xenopus laevis and Ambystoma mexicanum) were conducted at different developmental stages and by different methods to establish a simple amphibian-based assay. Test substance was pentachlorophenol sodium salt (PCP-Na). The endpoint was mortality and the 24-, 48-, 72-, and 96-h LC50 values were calculated by probit analysis. Interspecific differences in larval responses were not clear. Larval sensitivity tended to increase with larval age. Newly hatched larvae were most resistant to PCP-Na. During the tests of well-developed larvae, concentrations of dissolved oxygen and PCP-Na in the test solutions greatly dropped owing to uptake by the larvae. Therefore, middle-developed (2-week-old) larvae were most suitable for the test. Toxicity tests for volatile substances would be also possible using 2-week-old larvae in closed vessels. Test individuals should be kept individually to avoid the effects of poisonous skin secretions released from dead larvae.
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PMID:Examination of an amphibian-based assay using the larvae of Xenopus laevis and Ambystoma mexicanum. 1270 92

The ability of the carcinogenic environmental toxin pentachlorophenol (PCP, 1) to react with DNA bases has been assessed using MS and NMR. Treatment of PCP (100 microM) with horseradish peroxidase (HRP/H(2)O(2)) or myeloperoxidase (MPx/H(2)O(2), from human leukocytes) in the presence of excess deoxyguanosine (dG, 2 mM) led to the isolation and identification of the oxygen-bonded C8-dG nucleoside adduct 4. The reaction was absolutely specific for dG; no detectable adduct(s) was observed from HRP/H(2)O(2) and PCP in the presence of deoxyadenosine, deoxycytidine, or thymidine. Formation of 4 was also specific for peroxidase activation that is known to oxidize PCP into the phenoxyl radical. Treatment of PCP/dG with rat liver microsomes (RLM) failed to generate 4; instead, an adduct derived from the benzoquinone electrophile tetrachloro-1,4-benzoquinone (chloranil) was observed in the extracted ion chromatogram from the RLM/NADPH-treated PCP/dG sample. The adduct 4 is the first structurally characterized O-bonded phenolic DNA nucleoside adduct and highlights the ambident electrophilicity of phenoxyl radicals (O- vs C-) in reaction at C8 of dG, as we have previously demonstrated that the para-chlorophenolic toxin, ochratoxin A (2), reacts at C8 of dG to give the C-bonded adduct 3 via the intermediacy of the OTA phenoxyl radical. Given that PCP is known to induce DNA adduct formation in vivo and human exposure has been linked to incidences of leukemia, the adduct 4 could play a key role in PCP-mediated carcinogenesis.
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PMID:An oxygen-bonded c8-deoxyguanosine nucleoside adduct of pentachlorophenol by peroxidase activation: evidence for ambident c8 reactivity by phenoxyl radicals. 1287 Aug 83

Surfactant protein A (SP-A), a member of the collectin family, selectively binds to Pneumocystis carinii and mediates interactions between pathogen and host alveolar macrophages in vitro. To test the hypothesis that mice lacking SP-A have delayed clearance of Pneumocystis organisms and enhanced lung injury, wild-type C57BL/6 (WT) and SP-A-deficient mice (SP-A(-/-)) with or without selective CD4(+)-T-cell depletion were intratracheally inoculated with Pneumocystis organisms. Four weeks later, CD4-depleted SP-A-deficient mice had developed a more severe Pneumocystis infection than CD4-depleted WT (P. carinii pneumonia [PCP] scores of 3 versus 2, respectively). Whereas all non-CD4-depleted WT mice were free of PCP, intact SP-A(-/-) mice also had evidence of increased organism burden. Pneumocystis infection in SP-A-deficient mice was associated histologically with enhanced peribronchial and/or perivascular cellularity (score of 4 versus 2, SP-A(-/-) versus C57BL/6 mice, respectively) and a corresponding increase in bronchoalveolar lavage (BAL) cell counts. Increases in SP-D content, gamma interferon, interleukin-4, interleukin-5, and tumor necrosis factor alpha in BAL fluid occurred but were attenuated in PCP-infected SP-A(-/-) mice compared to WT mice. There were increases in total BAL NO levels in both infected groups, but nitrite levels were higher in SP-A(-/-) mice, indicating a reduction in production of higher oxides of nitrogen that was also reflected in lower levels of 3-nitrotyrosine staining in the SP-A(-/-) group. We conclude that despite increases in inflammatory cells, SP-A-deficient mice infected with P. carinii exhibit an enhanced susceptibility to the organism and attenuated production of proinflammatory cytokines and reactive oxygen-nitrogen species. These data support the concept that SP-A is a local effector molecule in the lung host defense against P. carinii in vivo.
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PMID:Enhanced lung injury and delayed clearance of Pneumocystis carinii in surfactant protein A-deficient mice: attenuation of cytokine responses and reactive oxygen-nitrogen species. 1538 4

Peptidoglycan (PGN) recognition proteins (PGRPs) are pattern recognition molecules of innate immunity that are conserved from insects to humans. Various PGRPs are reported to have diverse functions: they bind bacterial molecules, digest PGN, and are essential to the Toll pathway in Drosophila. One family member, bovine PGN recognition protein-S (bPGRP-S), has been found to bind and kill microorganisms in a PGN-independent manner, raising questions about the identity of the bPGRP-S ligand. Addressing this, we have determined the binding and microbicidal properties of bPGRP-S in a range of solutions approximating physiologic conditions. In this study we show that bPGRP-S interacts with other bacterial components, including LPS and lipoteichoic acid, with higher affinities than for PCP, as determined by their abilities to inhibit bPGRP-S-mediated killing of bacteria. Where and how PGRPs act in vivo is not yet clear. Using Immunogold electron microscopy, PGRP-S was localized to the dense/large granules of naive neutrophils, which contain the oxygen-independent bactericidal proteins of these cells, and to the neutrophil phagolysosome. In addition, Immunogold staining and secretion studies demonstrate that neutrophils secrete PGRP-S when exposed to bacteria. Bovine PGRP-S can mediate direct lysis of heat-killed bacteria; however, PGRP-S-mediated killing of bacteria is independent of this activity. Evidence that bPGRP-S has multiple activities and affinity to several bacterial molecules challenges the assumption that the PGRP family of proteins recapitulates the evolution of TLRs. Mammalian PGRPs do not have a single antimicrobial activity against a narrow range of target organisms; rather, they are generalists in their affinity and activity.
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PMID:Bovine peptidoglycan recognition protein-S: antimicrobial activity, localization, secretion, and binding properties. 1639 4

The carotid body's physiological role is to sense arterial oxygen, CO(2) and pH. It is however, also powerfully excited by inhibitors of oxidative phosphorylation. This latter observation is the cornerstone of the mitochondrial hypothesis which proposes that oxygen is sensed through changes in energy metabolism. All of these stimuli act in a similar manner, i.e. by inhibiting a background TASK-like potassium channel (K(B)) they induce membrane depolarization and thus neurosecretion. In this study we have evaluated the role of ATP in modulating K(B) channels. We find that K(B) channels are strongly activated by MgATP (but not ATP(4)(-)) within the physiological range (K(1/2) = 2.3 mm). This effect was mimicked by other Mg-nucleotides including GTP, UTP, AMP-PCP and ATP-gamma-S, but not by PP(i) or AMP, suggesting that channel activity is regulated by a Mg-nucleotide sensor. Channel activation by MgATP was not antagonized by either 1 mm AMP or 500 microm ADP. Thus MgATP is probably the principal nucleotide regulating channel activity in the intact cell. We therefore investigated the effects of metabolic inhibition upon both [Mg(2+)](i), as an index of MgATP depletion, and channel activity in cell-attached patches. The extent of increase in [Mg(2+)](i) (and thus MgATP depletion) in response to inhibition of oxidative phosphorylation were consistent with a decline in [MgATP](i) playing a prominent role in mediating inhibition of K(B) channel activity, and the response of arterial chemoreceptors to metabolic compromise.
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PMID:Modulation of TASK-like background potassium channels in rat arterial chemoreceptor cells by intracellular ATP and other nucleotides. 1761 4

OxyB catalyzes the first oxidative phenol coupling reaction in vancomycin biosynthesis. OxyB is a P450 hemoprotein whose activity is strictly dependent upon the presence of molecular oxygen. Here, it was shown that label from (18)O(2) is not incorporated into the monocyclic product during catalysis by OxyB. In addition, it was shown that OxyB can convert a model hexapeptide substrate containing (R)-Tyr6, instead of (S)-Tyr6, covalently linked as a C-terminal thioester to a peptidyl carrier protein (PCP-7S) derived from the vancomycin non-ribosomal peptide synthetase (NRPS), into the corresponding epimeric monocyclic product. The binding of this epimeric hexapeptide-PCP conjugate to the Fe(III) form of OxyB, as monitored by UV-vis spectroscopy, revealed a K(d)=35+/-5 microM. Thus, the enzyme reveals a surprising lack of stereospecificity in the binding and transformation of these epimeric substrates.
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PMID:New insights into the first oxidative phenol coupling reaction during vancomycin biosynthesis. 1806 78

The oxidation rate of pentachlorophenol, [C(6)HCl(5)O] which is used to control termites and as a general herbicide and also as the probable human's carcinogen, was investigated in an isothermal continuous tubular reactor under supercritical water oxidation (SCWO) conditions. The experiments were conducted at a temperature of 400-550 degrees C and a fixed pressure of 25 MPa, with a residence time that ranged from 6 s to 26 s. The conversion of PCP was monitored by analyzing total organic carbon (TOC) on the liquid effluent samples. The initial TOC concentrations of PCP were varied from 0.74 mmol/L to 2.91 mmol/L and the oxygen concentrations were varied from 0.46 mmol/L to 3.52 mmol/L. By taking into account the dependence of the oxidant and TOC concentration on the reaction rate, a global PCP oxidation rate was regressed from the data of 48 experiments, to a 95% confidence level. The resulting activation energy was determined to be 43.56 +/- 1.47 kJ/mol, and the pre-exponential factor was (1.92 +/- 0.46) x 10(2) L(1.16) mmol(-0.16) s(-1). The reaction orders for the PCP (based on TOC) and the oxidant were 0.74 +/- 0.02 and 0.42 +/- 0.05, respectively.
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PMID:Pentachlorophenol oxidation rates in supercritical water. 1807 81

Early effects of 0.0001-10 mM sodium pentachlorophenate (PCP-Na) on the green alga Chlorella pyrenoidosa Chick. S-39 involves a rapid (within 1-2 min) decrease in the light-induced oxygen evolution by algal cells. The suppressed relative yield of variable chlorophyll fluorescence in C. pyrenoidosa in the presence of high PCP-Na concentrations and its dynamics provide evidence for rapid inactivation of photosystem 2, which is not observed at low concentrations of the toxicant. An analysis of the induction curve of delayed chlorophyll fluorescence in algal cells suggests that PCP-Na at low concentrations disturbs the coupling of electron transport and phosphorylation, whereas at high concentrations it inhibits electron transport and decreases the energy potential of photosynthetic membranes. The early toxic effect of PCP-Na is responsible for subsequent impairment of C. pyrenoidosa productivity.
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PMID:[Early effect of sodium pentachlorophenate on photosynthetic activity of the alga Chlorella pyrenoidosa Chick S-39]. 1866 67

The reaction of molecular oxygen with iridium pincer hydride complexes, ((tBu)PCP)Ir(H)(X) [(tBu)PCP = kappa(3)-C(6)H(3)(CH(2)P(t)Bu(2))(2), X = Ph, H, CCPh], results in O(2) induced reductive elimination and formation of the novel dioxygen complexes ((tBu)PCP)Ir(O(2))(n) [n = 1 (), 2 ()].
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PMID:Reactions of iridium hydride pincer complexes with dioxygen: new dioxygen complexes and reversible O2 binding. 1880 27


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