Kalle Möbius,
Rodrigo Arias-Cartin,
Daniela Breckau,
Anna-Lena Hännig,
Katrin Riedmann,
Rebekka Biedendieck,
Susanne Schröder,
Dörte Becher,
Axel Magalon,
Jürgen Moser,
Martina Jahn and
Dieter Jahn
Abstract
Cellular energy generation uses membrane-localized electron transfer chains for ATP synthesis. Formed ATP in turn is consumed for the biosynthesis of cellular building blocks. In contrast, heme cofactor biosynthesis was found driving ATP generation via electron transport after initial ATP consumptio...
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PMID: 20484676
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Abstract
In photosynthetic organisms chlorophyll and heme biosynthesis is tightly regulated at various levels in response to environmental adaptation and plant development. The formation of 5-aminolevulinic acid (ALA) is the key regulatory step and provides adequate amounts of the common precursor molecule f...
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PMID: 20375109
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Abstract
We present the crystal structure of bsPPO bound to AF. Our structure shows that the AF molecule binds to a new site outside the previously identified inhibitor binding pocket. Most importantly, the benzene ring of the 2-nitrobenzoic acid moiety of AF lies parallel to the isoalloxazine ring of FAD at...
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PMID: 19944166
PDF is available here.
Abstract
Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) catalyzes the six-electron oxidation of protoporphyrinogen IX to the fully conjugated protoporphyrin IX. Eukaryotes and Gram-positive bacteria possess an oxygen-dependent, FAD-containing enzyme for this step, while the majority of Gram-negative bacteria l...
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PMID: 19583219
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Abstract
Our aim was to analyse the effects of variegate porphyria on haemoglobin levels, antioxidant enzyme activities and oxidative damage in circulating erythrocytes. Twelve women affected by variegate porphyria and 12 control healthy women participated in the study. Women affected by variegate porphyria...
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PMID: 19389274
PDF is available here.
Abstract
As the porphyria specialist centre of Switzerland, we perform the specialized analyses required for the diagnosis of all types of porphyrias, and give advice to patients, physicians and other laboratories. We therefore estimated that our data cover 80-90% of all diagnosed Swiss cases. A total of 217...
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PMID: 19350426
PDF is available here.
Kimberly A KA Dooley,
Paula G PG Fraenkel,
Nathaniel B NB Langer,
Bettina B Schmid,
Alan J AJ Davidson,
Gerhard G Weber,
Ken K Chiang,
Helen H Foott,
Caitlin C Dwyer,
Rebecca A RA Wingert,
Yi Y Zhou,
Barry H BH Paw,
Leonard I LI Zon and
Abstract
Homozygous mno mutant embryos have a defect in the protoporphyrinogen oxidase (ppox) gene, which encodes the enzyme that catalyzes the oxidation of protoporphyrinogen. Homozygous mutant embryos are deficient in hemoglobin, and by 36 hours post-fertilization are visibly anemic and porphyric. The hypo...
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PMID: 18550261
PDF is available here.
Abstract
We generated transgenic rice plants (Oryza sativa cv. Dongjin) over-expressing human protoporphyrinogen IX oxidase (PPO) with the aim to increase mitochondrial PPO activity and confer herbicide resistance (Lee et al., Pestic Biochem Physiol 80:65-74, 2004). The transgenic plants showed during furthe...
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PMID: 18437505
PDF is available here.
Abstract
Protoporphyrinogen oxidase (Protox, EC 1.3.3.4) has been identified as one of the most important action targets of herbicides. To search for novel Protox inhibitors, a series of title compounds 1, 2, and 3 were designed and synthesized by introducing three types of pharmacophores, cyclic imide, phen...
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PMID: 18298068
PDF is available here.
Abstract
We investigated erythroid-specific expression of the human PPOX gene. This gene encodes protoporphyrinogen oxidase, which is involved in synthesizing heme for red blood cells and heme as a cofactor for the respiratory cytochromes. In vitro luciferase transfection assays in human uninduced and hemin...
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PMID: 18191920
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Abstract
All affected individuals harboured mutations in heterozygous state. Nine novel mutations and 3 already reported mutations were identified. Six of the novel mutations were single nucleotide substitutions, 2 were small deletions and one a small insertion. Three single nucleotide substitutions and the...
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PMID: 18570668
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Abstract
We have studied the intracellular trafficking of Sit1 [ferrioxamine B (FOB) transporter] and Enb1 (enterobactin transporter) in Saccharomyces cerevisiae using green fluorescent protein (GFP) fusion proteins. Enb1 was constitutively targeted to the plasma membrane. Sit1 was essentially targeted to th...
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PMID: 17714436
PDF is available here.
Abstract
Photodynamic therapy (PDT), using protoporphyrin IX (PpIX) as a natural photosensitizer, may be a viable alternative therapy of retinoblastoma. In order to evaluate the potential value of PpIX, the expression profiles of genes involved in heme biosynthesis in human retinoblastoma WERI-Rb-1 and Y79 c...
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PMID: 17725098
PDF is available here.
Abstract
PPO (protoporphyrinogen IX oxidase) catalyses the flavin-dependent six-electron oxidation of protogen (protoporphyrinogen IX) to form proto (protoporphyrin IX), a crucial step in haem and chlorophyll biosynthesis. The apparent K(m) value for wild-type tobacco PPO2 (mitochondrial PPO) was 1.17 muM, w...
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PMID: 17134376
PDF is available here.
Abstract
We report two zebrafish heme synthesis enzymes, uroporphyrinogen III synthase (UROS) and protoporphyrinogen oxidase (PPO) that are well conserved in comparison to their human counterparts. Both UROS and PPO formed pairs of bilateral stripes in the lateral plate mesoderm at the 15-somite stage. At 24...
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PMID: 17364814
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Abstract
We present the structure of protoporphyrinogen IX oxidase from Myxococcus xanthus, an enzyme with similar catalytic properties to human protoporphyrinogen IX oxidase that also binds the common plant herbicide, acifluorfen. In the native structure, the planar porphyrinogen substrate is mimicked by a...
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PMID: 17046834
PDF is available here.
Abstract
I in transgenic tobacco plants, which showed reduced growth rate and necrotic leaf damage. The cytotoxic effect is attributed to accumulation of photodynamically acting protoporphyrin. The expression levels of PPOX I mRNA and protein and the cellular enzyme activities were reduced to similar extents...
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PMID: 17059408
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Abstract
Single strand conformational analysis (SSCP) of DNA allowed the detection of the following mutations: W224R, 746delT: exon 7, 1077-1082insC: exon 10, and IVS6+2T-->A. Mutation was present in 19 of the 139 members of the families studied. Clinical manifestations or biochemical alterations were checke...
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PMID: 16922948
PDF is available here.
Abstract
Herbicides that act by inhibiting protoporphyrinogen oxidase (PPO) are widely used to control weeds in a variety of crops. The first weed to evolve resistance to PPO-inhibiting herbicides was Amaranthus tuberculatus, a problematic weed in the midwestern United States that previously had evolved mult...
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PMID: 16894159
PDF is available here.
Abstract
Six of the eight index patients presented with only skin symptoms, and one with only neurological symptoms. Another patient had both skin and neurological symptoms. Faecal porphyrin excretion was elevated in all patients thus enabling diagnosis. Four different mutations including three novel mutatio...
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PMID: 16947091
PDF is available here.
Abstract
We propose a mechanism for protoporphyrinogen oxidase targeting to the mitochondrion....
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PMID: 16621625
PDF is available here.
Abstract
The effects of 40 herbicides with nine modes of action on the green alga Raphidocelis subcapitata were studied by 96-h acute toxicity tests. Results showed that the EC50 of the herbicides with respect to the photosynthetic processes of R. subcapitata ranged from 0.0007 to 4.2286 mgL(-1). Photosynthe...
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PMID: 16406601
PDF is available here.
Abstract
We identified a missense mutation in exon 7 on the paternal allele and a frameshift mutation in exon 13 on the maternal allele of the protoporphyrinogen oxidase gene that harbours the mutations underlying VP. This is the first homozygous case of VP in South America. As VP represents the most frequen...
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PMID: 16433813
PDF is available here.
Abstract
We identified a nonsense mutation in the porphobilinogen deaminase gene on chromosome 11q23.3, which harbors the mutations causing acute intermittent porphyria, as the underlying genetic defect in Chester porphyria. However, we could not detect a mutation in the coding or the promotor region of the...
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PMID: 17298217
PDF is available here.
Abstract
We performed molecular genetic studies in 13 Chilean families by PCR amplification of the PPOX gene, conformation sensitive gel electrophoresis, and automated DNA sequencing. In five symptomatic patients from different families, respectively, the biochemical data confirmed the diagnosis of VP. In se...
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PMID: 17146940
PDF is available here.
Abstract
We report that in the green alga Chlamydomonas reinhardtii, PPO and FeC are each encoded by a single gene. Phylogenetic analysis indicates that C. reinhardtii PPO and FeC are most closely related to plant counterparts that are located only in chloroplasts. Immunoblotting results suggest that C. rein...
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PMID: 16306143
PDF is available here.
Abstract
The S-adenosylmethionine (AdoMet) radical enzyme oxygen-independent coproporphyrinogen III oxidase HemN catalyzes the oxidative decarboxylation of coproporphyrinogen III to protoporphyrinogen IX during bacterial heme biosynthesis. The recently solved crystal structure of Escherichia coli HemN reveal...
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PMID: 15967800
PDF is available here.
Abstract
Several Arabidopsis mutants of the ecotype Dijon were isolated that show resistance to the herbicide acifluorfen, which inactivates protoporphyrinogen oxidase (PPOX), an enzyme of tetrapyrrole biosynthesis. This enzyme provides protoporphyrin for both Mg chelatase and ferrochelatase at the branchpoi...
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PMID: 15815918
PDF is available here.
Abstract
We analyzed the herbicidal and antioxidant defense responses of transgenic rice plants that overexpressed the Myxococcus xanthus protoporphyrinogen oxidase gene. Leaf squares of the wild-type incubated with oxyfluorfen were characterized by necrotic leaf lesions and increases in conductivity and mal...
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PMID: 15890521
PDF is available here.
Abstract
We report that the complete leader is necessary for translocation and that this process is not haem-sensitive in vivo. PPO (protoporphyrinogen oxidase) lacks a typical mitochondrial targeting leader sequence and was found to be effectively targeted by just 17 N-terminal residues. Bacillus subtilis P...
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PMID: 15482256
PDF is available here.
Abstract
The structures of methyl 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoate, C15H9ClF3N3O5, (I), methyl 2-chloro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzoate, C14H10ClF3N2O4, (II), and 2-[4-chloro-2-fluoro-5-(prop-2-ynyloxy)phenyl]-4-(trifluoromethyl)piper...
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PMID: 15695911
PDF is available here.
Abstract
A patient, who presented with abdominal pain and severe photosensitivity that resulted in scarring and mutilation of the fingers, nose and ears, was referred for biochemical assessment of porphyria and DNA screening. Although these clinical manifestations were suggestive of both acute porphyria and...
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PMID: 15660919
PDF is available here.
Abstract
Resistance to acetolactate synthase (ALS)-inhibiting herbicides in Brazil has been documented for six species. The probability to select biotypes of Euphorbia heterophylla (EPPHL) with multiple resistance increases in the same order of magnitude as the use of other herbicides belonging to only one m...
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PMID: 15656167
PDF is available here.
Abstract
We have determined the characteristic frequencies and the "hot spot" amino acids, and predicted the location of proteins' active site(s). Several proteins that potentially belong to the PpOI functional group were also analysed to distinguish their viability in this role....
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PMID: 15712584
PDF is available here.
Abstract
The equilibrium geometries, electronic structures, and electrostatic potentials of a series of substituted phenyl triazolinones, a kind of important protoporphyrinogen oxidase (Protox) inhibitors, had been investigated using density functional theory (DFT) method at the B3LYP/6-31G(d,p) basis set. T...
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PMID: 15519162
PDF is available here.
Abstract
The equilibrium geometries, electronic structures, and electrostatic potentials of a series of substituted phenyl triazolinones of protoporphyrinogen oxidase (PPO) inhibitors have been investigated by using the density functional theory (DFT) method. The quantum chemical descriptors, highest occupie...
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PMID: 15389747
PDF is available here.
Abstract
The clinical penetrance of VP in our family is approximately 40%. Many more subjects with VP are diagnosed in an asymptomatic phase than previously, and the acute attack is now an uncommon manifestation of VP. Plasma scanning is more sensitive than faecal porphyrin analysis, but neither is sufficien...
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PMID: 15327556
PDF is available here.
Abstract
Plasma scanning is a more sensitive and specific test for VP than fecal porphyrin analysis. Neither test is sensitive in children, and both are less sensitive in asymptomatic carriers than in symptomatic cases. DNA analysis therefore remains the preferred method for the identification of carriers, p...
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PMID: 14976149
PDF is available here.
Abstract
We present the crystal structure of mitochondrial PPO from tobacco complexed with a phenyl-pyrazol inhibitor. PPO forms a loosely associated dimer and folds into an FAD-binding domain of the p-hydroxybenzoate-hydrolase fold and a substrate-binding domain that enclose a narrow active site cavity bene...
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PMID: 15057273
PDF is available here.
Abstract
We have recently demonstrated that in an autosomal dominant porphyria, erythropoietic protoporphyria (EPP), the coinheritance of a ferrochelatase (FECH) gene defect and of a wild-type low-expressed FECH allele is generally involved in the clinical expression of EPP. This mechanism may provide a mode...
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PMID: 14669009
PDF is available here.
Abstract
We have fused human PPOXs containing N-terminal deletions, C-terminal deletions or missense mutations to yellow fluorescent protein (YFP) and have used these constructs to investigate the mitochondrial import of PPOX in human cells. We show that all the information required for efficient import is c...
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PMID: 14535846
PDF is available here.
Abstract
Our QSAR analysis using the quantum chemical descriptors calculated at the B3LYP/6-31G(d,p) level led to a useful explicit correlation relationship, i.e. pI50 = -5.7414 + 0.1424alpha - 0.0003alpha2 - 0.4546FNC* + 0.2974QN** (n=26, R2=0.87), showing that descriptors mean molecular polarizability, alp...
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PMID: 15554680
PDF is available here.
Abstract
In an effort to asses the effect of Val311Met point mutation of Bacillus subtilis protoporphyrinogen oxidase on the resistance to diphenyl ether herbicides, a Val311Met point mutant of B. subtilis protoporphyrinogen oxidase was prepared, heterologously expressed in Escherichia coli, and the purified...
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PMID: 12941291
PDF is available here.
Abstract
We report the isolation of plant protoporphyrinogen oxidase (PPO) genes and the isolation of herbicide-tolerant mutants. Subsequently, an Arabidopsis double mutant (Y426M + S305L) was used to develop a selectable marker system for Agrobacterium tumefaciens-mediated transformation of maize (Zea mays)...
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PMID: 12972658
PDF is available here.
Abstract
Maize (Zea mays) protoporphyrinogen IX oxidase (PPO: EC 1.3.3.4) possesses a chloroplast transit peptide (CTP) that delivers the enzyme into the chloroplast. The cleavage site yielding the mature protein was predicted by using the ChloroP software and by comparing conserved regions of the available...
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PMID: 13679054
PDF is available here.
Abstract
The effects of various protoporphyrinogen oxidase (PPOX) mutations responsible for variegate porphyria (VP), the roles of the arginine-59 residue and the glycines in the conserved flavin binding site, in catalysis and/or cofactor binding, were examined. Wild-type recombinant human PPOX and a selecti...
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PMID: 12922165
PDF is available here.
Abstract
Variegate porphyria (VP) is an autosomal-dominant disorder that is caused by inheritance of a partial deficiency of the enzyme protoporphyrinogen oxidase (EC 1.3.3.4). It is characterized by cutaneous photosensitivity and/or various neurological manifestations. Protoporphyrinogen oxidase catalyses t...
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PMID: 12859407
PDF is available here.
Abstract
We analyze the expression of three xanthophyll biosynthetic genes (i.e. beta-carotene hydroxylase [bhy], zeaxanthin epoxidase [zep], and violaxanthin de-epoxidase [vde]) during de-etiolation of seedlings of tobacco (Nicotiana tabacum L. cv Samsun) under different light conditions. White-light illumi...
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PMID: 12857831
PDF is available here.
Abstract
These results indicate that either cytoplasm or plastid expression of B. subtilis Protox in rice can upregulate the porphyrin pathway leading to increase in photosynthetic efficiency in plants....
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PMID: 12913289
PDF is available here.
Abstract
We have investigated the signal sequence for mitochondrial transport of mutants (I12T, 78insC, IVS2-2a-->c, 338G-->C, R152C, 470A-->C, and L401F) and the wild type protoporphyrinogen oxidase (PPOX), which is the penultimate enzyme in the heme biosynthesis. We constructed the corresponding green fluo...
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PMID: 12556518
PDF is available here.
Abstract
We report a genetic analysis of VP in Italy, and the identification of six novel and three previously characterised mutations from nine affected individuals and families. Among those newly identified, two mutations were small deletions (c.418_419delAA; c.759delA), leading to the formation of prematu...
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PMID: 12655566
PDF is available here.
Abstract
We provide an update on the molecular diagnosis of porphyrias in Italy and a flow-chart to facilitate the identification of mutations in heme biosynthetic genes. The molecular analysis has allowed us to identify the molecular defect underlying the disease in 66 probands with different porphyrias [ac...
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PMID: 12699245
PDF is available here.