Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0220723 (PCA)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A longitudinal study of circulating autoantibodies in the sera of 48 BB rats was performed by indirect immunofluorescence. No pancreatic islet cell, adrenocortical, or thyroid microsomal autoantibodies were found. However, autoantibodies reactive to gastric parietal cells (PCA), smooth muscle, and thyroid colloidal antigens were identified, PCA were not detected in Wistar-Furth or BB x Wistar-Furth F1 hybrid rats. The range of ages at the time of first appearance of PCA was the same as that of onset of insulin-dependent diabetes (IDD) in the BB rats, suggesting that the processes leading to PCA and IDD were occurring at the same time of life in these animals. The presence of PCA was associated with degrees of lymphocytic gastritis and with squamous metaplasia of the gastric mucosa in the oldest BB rats (9 mo of age). Levels of serum iron and vitamin B12 did not differ between PCA-positive and PCA-negative BB rats, nor was achiorhydria found in any rat studied. The identification of PCA (and chronic gastritis) and other autoantibodies in the BB rat suggests that these animals have an underlying autoimmune diathesis. These findings thus provide indirect support for an autoimmune pathogenesis for IDD in the BB rat.
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PMID:Gastric parietal cell and other autoantibodies in the BB rat. 675 47

Protocatechuate 3,4-dioxygenase (3,4-PCD) utilizes a ferric ion to catalyze the aromatic ring cleavage of 3,4-dihydroxybenzoate (PCA) by incorporation of both atoms of dioxygen to yield beta-carboxy-cis, cis-muconate. The crystal structures of the anaerobic 3,4-PCD.PCA complex, aerobic complexes with two heterocyclic PCA analogs, 2-hydroxyisonicotinic acid N-oxide (INO) and 6-hydroxynicotinic acid N-oxide (NNO), and ternary complexes of 3,4-PCD.INO.CN and 3,4-PCD. NNO.CN have been determined at 2.1-2.2 A resolution and refined to R-factors between 0.165 and 0.184. PCA, INO, and NNO form very similar, asymmetrically chelated complexes with the active site Fe3+ that result in dissociation of the endogenous axial tyrosinate Fe3+ ligand, Tyr447 (147beta). After its release from the iron, Tyr447 is stabilized by hydrogen bonding to Tyr16 (16alpha) and Asp413 (113beta) and forms the top of a small cavity adjacent to the C3-C4 bond of PCA. The equatorial Fe3+ coordination site within this cavity is unoccupied in the anaerobic 3,4-PCD.PCA complex but coordinates a solvent molecule in the 3,4-PCD.INO and 3,4-PCD.NNO complexes and CN- in the 3,4-PCD.INO.CN and 3,4-PCD.NNO.CN complexes. This shows that an O2 analog can occupy the cavity and suggests that electrophilic O2 attack on PCA is initiated from this site. Both the dissociation of the endogenous Tyr447 and the expansion of the iron coordination sphere are novel features of the 3,4-PCD. substrate complex which appear to play essential roles in the activation of substrate for O2 attack. Together, the structures presented here and in the preceding paper [Orville, A. M., Elango, N. , Lipscomb, J. D., & Ohlendorf, D. H. (1997) Biochemistry 36, 10039-10051] provide atomic models for several steps in the reaction cycle of 3,4-PCD and related Fe3+-containing dioxygenases.
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PMID:Crystal structures of substrate and substrate analog complexes of protocatechuate 3,4-dioxygenase: endogenous Fe3+ ligand displacement in response to substrate binding. 925

The crystal structure of the anaerobic complex of Pseudomonas putida protocatechuate 3,4-dioxygenase (3,4-PCD) bound with the alternative substrate, 3,4-dihydroxyphenylacetate (HPCA), is reported at 2.4 A resolution and refined to an R factor of 0.17. Formation of the active site Fe(III).HPCA chelated complex causes the endogenous axial tyrosinate, Tyr447 (147beta), to dissociate from the iron and rotate into an alternative orientation analogous to that previously observed in the anaerobic 3,4-PCD.3,4-dihydroxybenzoate complex (3, 4-PCD.PCA) [Orville, A. M., Lipscomb, J. D., & Ohlendorf, D. H. (1997) Biochemistry 36, 10052-10066]. Two orientations of the aromatic ring of HPCA related by an approximate 180 degrees rotation within the active site are consistent with the electron density. Resonance Raman (rR) spectroscopic data from Brevibacteriumfuscum 3,4-PCD.HPCA complex in solution reveals low frequency rR vibrational bands between 500 and 650 cm-1 as well as a band at approximately 1320 cm-1 which are diagnostic of a HPCA. Fe(III) chelate complex. 18O labeling of HPCA at either the C4 or C3 hydroxyl group unambiguously establishes the vibrational coupling modes associated with the five-membered chelate ring system. Analysis of these data suggests that the Fe(III)-HPCAO4 bond is shorter than the Fe(III)-HPCAO3 bond. This consequently favors the model for the crystal structure in which the C3 phenolic function occupies the Fe3+ ligand site opposite the endogenous ligand Tyr408(Oeta) (108beta). This is essentially the same binding orientation as proposed for PCA in the crystal structure of the anaerobic 3,4-PCD.PCA complex based solely on direct modeling of the 2Fo - Fc electron density and suggests that this is the conformation required for catalysis.
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PMID:Crystal structure and resonance Raman studies of protocatechuate 3,4-dioxygenase complexed with 3,4-dihydroxyphenylacetate. 929 71

The geometric and electronic structure of NO bound to reduced protocatechuate 3,4-dioxygenase and its substrate (3,4-dihydroxybenzoate, PCA) complex have been examined by X-ray absorption (XAS), UV-vis absorption (Abs), magnetic circular dichroism (MCD), and variable temperature variable field (VTVH) MCD spectroscopies. The results are compared to those previously published on model complexes described as [FeNO]7 systems in which an S = 5/2 ferric center is antiferromagnetically coupled to an S = 1 NO-. XAS pre-edge analysis indicates that the Fe-NO units in FeIIIPCD[NO-] and FeIIIPCD[PCA,NO-] lack the greatly increased pre-edge intensity representative of most [FeNO]7 model sites. Furthermore, from extended X-ray absorption fine structure (EXAFS) analysis, the FeIIIPCD[NO-] and FeIIIPCD[PCA,NO-] active sites are shown to have an Fe-NO distance of at least 1.91 A, approximately 0.2 A greater than those found in the model complexes. The weakened Fe-NO bond is consistent with the overall lengthening of the bond lengths and the fact that VTVH MCD data show that NO(-)-->FeIII CT transitions are no longer polarized along the z-axis of the zero-field splitting tensor. The weaker Fe-NO bond derives from the strong donor interaction of the endogenous phenolate and substrate catecholate ligands, which is observed from the increased intensity in the CT region relative to that of [FeNO]7 model complexes, and from the shift in XAS edge position to lower energy. As NO is an analogue of O2, the effect of endogenous ligand donor strength on the Fe-NO bond has important implications with respect to O2 activation by non-heme iron enzymes.
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PMID:Spectroscopic studies of the effect of ligand donor strength on the Fe-NO bond intradiol dioxygenases. 1269 16

Pseudomonas fluorescens 2-79RN(10) protects wheat against take-all disease caused by Gaeumannomyces graminis var. tritici; however, the level of protection in the field varies from site to site. Identification of soil factors that exert the greatest influence on disease suppression is essential to improving biocontrol. In order to assess the relative importance of 28 soil properties on take-all suppression, seeds were treated with strain 2-79RN(10) (which produces phenazine-1-carboxylate [PCA(+)]) or a series of mutants with PCA(+) and PCA(-) phenotypes. Bacterized seeds were planted in 10 soils, representative of the wheat-growing region in the Pacific Northwest. Sixteen soil properties were correlated with disease suppression. Biocontrol activity of PCA(+) strains was positively correlated with ammonium-nitrogen, percent sand, soil pH, sodium (extractable and soluble), sulfate-sulfur, and zinc. In contrast, biocontrol was negatively correlated with cation-exchange capacity (CEC), exchangeable acidity, iron, manganese, percent clay, percent organic matter (OM), percent silt, total carbon, and total nitrogen. Principal component factor analysis of the 16 soil properties identified a three-component solution that accounted for 87 percent of the variance in disease rating (biocontrol). A model was identified with step-wise regression analysis (R(2) = 0.96; Cp statistic = 6.17) that included six key soil properties: ammonium-nitrogen, CEC, iron, percent silt, soil pH, and zinc. As predicted by our regression model, the biocontrol activity of 2-79RN(10) was improved by amending a soil low in Zn with 50 micro g of zinc-EDTA/g of soil. We then investigated the negative correlation of OM with disease suppression and found that addition of OM (as wheat straw) at rates typical of high-OM soils significantly reduced biocontrol activity of 2-79RN(10).
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PMID:Identification and manipulation of soil properties to improve the biological control performance of phenazine-producing Pseudomonas fluorescens. 1278 34

The impact of acid rock drainage (ARD) and eutrophication on microbial communities in stream sediments above and below an abandoned mine site in the Adelaide Hills, South Australia, was quantified by PLFA analysis. Multivariate analysis of water quality parameters, including anions, soluble heavy metals, pH, and conductivity, as well as total extractable metal concentrations in sediments, produced clustering of sample sites into three distinct groups. These groups corresponded with levels of nutrient enrichment and/or concentration of pollutants associated with ARD. Total PLFA concentration, which is indicative of microbial biomass, was reduced by >70% at sites along the stream between the mine site and as far as 18 km downstream. Further downstream, however, recovery of the microbial abundance was apparent, possibly reflecting dilution effect by downstream tributaries. Total PLFA was >40% higher at, and immediately below, the mine site (0-0.1 km), compared with sites further downstream (2.5-18 km), even after accounting for differences in specific surface area of different sediment samples. The increased microbial population in the proximity of the mine source may be associated with the presence of a thriving iron-oxidizing bacteria community as a consequence of optimal conditions for these organisms while the lower microbial population further downstream corresponded with greater sediments' metal concentrations. PCA of relative abundance revealed a number of PLFAs which were most influential in discriminating between ARD-polluted sites and the rest of the sites. These PLFA included the hydroxy fatty acids: 2OH12:0, 3OH12:0, 2OH16:0; the fungal marker: 18:2omega6; the sulfate-reducing bacteria marker 10Me16:1omega7; and the saturated fatty acids 12:0, 16:0, 18:0. Partial constrained ordination revealed that the environmental parameters with the greatest bearing on the PLFA profiles included pH, soluble aluminum, total extractable iron, and zinc. The study demonstrated the successful application of PLFA analysis to rapidly assess the toxicity of ARD-affected waters and sediments and to differentiate this response from the effects of other pollutants, such as increased nutrients and salinity.
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PMID:The use of phospholipid fatty acid analysis to measure impact of acid rock drainage on microbial communities in sediments. 1569 50

This paper shows the results of a preliminary study of air monitoring in the province of Lecce (Apulia, Southern Italy). In particular, the attention has been focused on the determination of the PM-10 level and of the concentration of nine metals (Cd, Cr, Cu, Fe, Mn, Ni, Pb, V and Zn) present on the filters which were collected in two towns (Lecce and Campi Salentina) from 2002 until 2003. The metals have been chosen on the basis of their toxicity and of their possible use as chemical tracers. The results have proved that PM-10 values and metals concentrations did not show substantial difference between the two towns and that PM-10 level and lead concentration are below the limit established by Italian law in force. The experiments have demonstrated a high correlation between iron and manganese in both sampling sites; this could be attributed to pollution of metallurgical origin. Multivariate statistical analysis, carried out by HCA and PCA methods, has been used in order to differentiate samples in relation to sampling sites, sampling period and meteorological conditions.
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PMID:PM-10 and heavy metals in particulate matter of the province of Lecce (Apulia, Southern Italy). 1580 Nov 74

The active site Fe(III) of protocatechuate 3,4-dioxygenase (3,4-PCD) from Pseudomonas putida is ligated axially by Tyr447 and His462 and equatorially by Tyr408, His460, and OH(-). Tyr447 and OH(-) are displaced as protocatechuate (3,4-dihydroxybenzoate, PCA) chelates the iron and appear to serve as in situ bases to promote this process. The role(s) of Tyr408 is (are) explored here using mutant enzymes that exhibit less than 0.1% wild-type activity. The X-ray crystal structures of the mutants and their PCA complexes show that the new shorter residues in the 408 position cannot ligate the iron and instead interact with the iron through solvents. Moreover, PCA binds as a monodentate rather than a bidentate ligand, and Tyr447 fails to dissociate. Although the new residues at position 408 do not directly bind to the iron, large changes in the spectroscopic and catalytic properties are noted among the mutant enzymes. Resonance Raman features show that the Fe-O bond of the monodentate 4-hydroxybenzoate (4HB) inhibitor complex is significantly stronger in the mutants than in wild-type 3,4-PCD. Transient kinetic studies show that PCA and 4HB bind to 3,4-PCD in a fast, reversible step followed by a step in which coordination to the metal occurs; the latter process is at least 50-fold slower in the mutant enzymes. It is proposed that, in wild-type 3,4-PCD, the Lewis base strength of Tyr408 lowers the Lewis acidity of the iron to foster the rapid exchange of anionic ligands during the catalytic cycle. Accordingly, the increase in Lewis acidity of the iron caused by substitution of this residue by solvent tends to make the iron substitution inert. Tyr447 cannot be released to allow formation of the usual dianionic PCA chelate complex with the active site iron, and the rate of electrophilic attack by O(2) becomes rate limiting overall. The structures of the PCA complexes of these mutant enzymes show that hydrogen-bonding interactions between the new solvent ligand and the new second-sphere residue in position 408 allow this residue to significantly influence the spectroscopic and kinetic properties of the enzymes.
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PMID:Roles of the equatorial tyrosyl iron ligand of protocatechuate 3,4-dioxygenase in catalysis. 1610 Dec 86

The concentration and speciation of six heavy metals in sediments of eight sampling sites of Haihe River were investigated. The metals, namely Cd, Cu, Co, Ni, Mn and Pb were considered. By using sequential extraction (SE), the total metals were divided into five fractions: exchangeable, carbonate bound, iron/manganese oxide bound, sulfides and organic matter fraction and residual fraction. A multivariate statistical approach (principal component analysis, PCA) was used to evaluate the contamination of heavy metals by the total levels and chemical forms, respectively. The results showed that the total metals concentration (TMC) could not provide sufficient and accurate information because the mobility, bioavailability and toxicity of metals depend not only on their total concentration but also on the physicochemical form in which they occur.
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PMID:Application of chemometrics methods for the estimation of heavy metals contamination in river sediments. 1615 75

For various shielding and reactor pressure vessel dosimetry applications, a pseudo-problem-independent neutron-photon coupled MATXS-format library, based on the last release of ENDF/B-VI, has been generated as a part of the update program for KASHIL-E6, which was based on ENDF/B-VI.5. It has a VITAMIN-B6 neutron and photon energy group structures, i.e. 199 groups for the neutron and 42 groups for the photon. The neutron and photon weighting functions and the Legendre orders of scattering are the same as in KASHIL-E6. The library has been validated through some benchmarks: the PCA-REPLICA and NESDIP-2 experiments for the light-water reactor (LWR) pressure vessel facility benchmark, the Winfrith Iron 88 experiment for the validation of the iron data and the Winfrith Graphite experiment for the validation of the graphite data. These calculations were performed by the TRANSX/DANTSYS code system. In addition, the substitutions of the JENDL-3.3 and JEFF-3.0 data for Fe, Cr, Cu and Ni, which are very important nuclides for shielding analyses, were investigated to estimate the effects on the benchmark calculation results.
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PMID:Generation and validation of a shielding library based on ENDF/B-VI.8. 1638 18


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