Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1832526 (PCC)
 5,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A homozygous insertion mutant with the inactivated clpP2 gene, which encodes the proteolytic subunit of ATP-dependent peptidase, was obtained in the unicellular cyanobacterium Synechocystis sp. PCC 6803. The mutant cannot grow under photoautotrophic conditions, but cells grown under heterotrophic conditions in a glucose-containing medium have active photosystems I and II (PS I and PS II). The loss of capacity for photoautotrophic growth is determined by a high sensitivity of mutant cells to the inactivating effect of light. Their incubation under light with an intensity above 10 microE m-2 s-1 inhibits cell growth in culture and causes degradation of photosynthetic pigments. It is proposed that the ClpP2 peptidase is involved in the protection of Synechocystis 6803 cells from photoinhibition.
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PMID:[clpP2 gene encoding peptidase in cyanobacteria Synechocystis sp. PCC 6803 controls the sensitivity of cells to photoinhibition]. 1143 41

Fatty acid composition of the membrane lipids in the mesophilic cyanobacterium Synechocystis sp. PCC 6803 was altered in earlier work by targeted mutagenesis of genes for fatty acid desaturases. In this work, cells of several mutant strains, depleted in the unsaturated fatty acids in membrane lipids, were grown at 34 degrees C. Spheroplasts (permeabilized cells) were prepared by lysozyme digestion of the cell wall followed by gentle osmotic shock. The bioenergetic parameters ATP formation, electron transport, and H+ uptake were measured at various temperatures. All three bioenergetic parameters for spheroplasts from wild-type cells (which had abundant polyunsaturated fatty acids) were active down to the lowest temperatures used (1 degrees - 2 degrees C). In two strains, which lacked the capacity to desaturate fatty acids at the A 12 position and at the A 12 and A6 positions (designated as desA- and desA-/desD-, respectively), the spheroplasts lost the capacity to form ATP (measured as phenazine methosulfate cyclic phosphorylation) at about 5 degrees C but retained electron transport (water oxidation-dependent ferricyanide reduction) and H+ uptake linked to phenazine methosulfate cyclic electron transport. It appears that the absence of the unsaturation of fatty acids in the A 12 and A6 positions blocks the ability of the photosynthetic membranes to couple a bioenergetically competent proton-motive force to the ATP formation mechanism at temperatures below 5 degrees C. It remains to be determined whether the loss of ATP formation in the mutant strains is the failure of available protons to properly flow into the CF0CF1-ATP synthase or a failure in the CF1 part of the complex in coupling the dissipative H+ flow to the enzyme mechanism of the synthase.
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PMID:Bioenergetic responses of Synechocystis 6803 fatty acid desaturase mutants at low temperatures. 1145 19

Chryseobacterium meningosepticum is an aerobic Gram-negative rod widely distributed in natural environments. Unlike many bacteria, it produces a phosphate-irrepressible periplasmic alkaline phosphatase (AP). This work describes cloning of the gene encoding that enzyme from C. meningosepticum CCUG 4310 (NCTC 10585), and preliminary characterization of its product. The gene, named pafA, encodes a protein (PafA) of 546 amino acids with a calculated molecular mass of the mature peptide of 58682 Da. PafA exhibits high sequence identity with the PhoV AP of Synechococcus PCC 7942 (49.9% identity) and with the Cda Ca(2+)-dependent ATPase of Myroides odoratus (51.9% identity), while being more distantly related to the PhoD AP of Zymomonas mobilis (22.1% identity) and to the PhoA AP of Escherichia coli (14.0% identity). PafA was partially purified; it exhibits optimal activity at pH 8.5 and is active towards a broad spectrum of substrates including both phosphomonoesters and ATP, with preferential activity for the latter compound. The present findings allow definition of a new family of APs including 60 kDa, periplasmic enzymes whose expression is not influenced by freely available P(i) in the medium. Moreover, PafA can be considered an evolutionary intermediate between Ca(2+)-ATPase of M. odoratus and the APs PhoV of Synechococcus PCC 7942 and PhoD of Z. mobilis.
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PMID:The Chryseobacterium meningosepticum PafA enzyme: prototype of a new enzyme family of prokaryotic phosphate-irrepressible alkaline phosphatases? 1157 61

Propionyl-CoA carboxylase (PCC, EC 6.4.1.3) is a mitochondrial, biotin-dependent enzyme that functions in the catabolism of branched-chain amino acids, fatty acids with odd-numbered chain lengths, and other metabolites. It catalyzes the ATP-dependent carboxylation of propionyl-CoA to d-methylmalonyl-CoA. PCC is composed of two types of subunits, likely as alpha4beta4 or alpha6beta6, with the alpha subunit containing the covalently bound biotin prosthetic group. A genetic deficiency of PCC activity causes propionic acidemia, a potentially fatal disease with onset in severe cases in the newborn period. Affected patients may have mutations of either the PCCA or PCCB gene. In this study, we have determined the structure of the human PCCA gene which, at the present time, is only partially represented in the databases. Based on reported ESTs and confirmed by RT-PCR, we also redefine the translation initiation codon to a position 75 nucleotides upstream of the currently accepted initiation codon. We show the distribution of mutations, including three identified in this study, and renumber all reported mutations to count from the new initiation codon. The gene spans more than 360 kb and consists of 24 exons ranging from 37 to 335 bp in length. The introns range in size from 104.bp to 66 kb. We have also determined the nucleotide sequence of approximately 1 kb of the 5'-flanking region upstream of the ATG translation initiation site. The proximal 400 bp of the 5'-flanking region shows a high G + C content (67%) and is part of a putative 1-kb CpG island that extends into exon 1 and part of intron 1. The putative promoter lacks a TATA box but contains two AP-1 sites and a conservatively defined consensus GC box, the latter characteristic of the core binding sequence of the Sp1 transcription factor.
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PMID:Structure of the PCCA gene and distribution of mutations causing propionic acidemia. 1159 20

Cyclic electron transport around photosystem (PS) I is believed to play a role in generation of ATP required for adaptation to stress in cyanobacteria and plants. However, elucidation of the pathway(s) of cyclic electron flow is difficult because of low rates of this electron flow relative to those of linear photosynthetic and respiratory electron transport. We have constructed a strain of Synechocystis sp. PCC 6803 that lacks both PSII and respiratory oxidases and that, consequently, neither evolves nor consumes oxygen. However, this strain is still capable of cyclic electron flow around PSI. The photoheterotrophic growth rate of this strain increased with light intensity up to an intensity of about 25 mumol photons m-2 s-1, supporting the notion that cyclic electron flow contributes to ATP generation in this strain. Indeed, the ATP-generating ability of PSI is demonstrated by the fact that the PSII-less oxidase-less strain is able to grow at much higher salt concentrations than a strain lacking PSI. A quinone electrode was used to measure the redox state of the plastoquinone pool in vivo in the various strains used in this study. In contrast to what is observed in chloroplasts, the plastoquinone pool was rather reduced in darkness and was oxidized in the light. This is in line with significant electron donation by respiratory pathways (NADPH dehydrogenase and particularly succinate dehydrogenase) in darkness. In the light, the pool becomes oxidized due to the presence of much more PSI than PSII. In the oxidase-less strains, the plastoquinone pool was very much reduced in darkness and was oxidized in the light by PSI. Photosystem II activity did not greatly alter the redox state of the plastoquinone pool. The results suggest that cyclic electron flow around PSI can contribute to generation of ATP, and a strain deficient in linear electron transport pathways provides an excellent model for further investigations of cyclic electron flow.
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PMID:A strain of Synechocystis sp. PCC 6803 without photosynthetic oxygen evolution and respiratory oxygen consumption: implications for the study of cyclic photosynthetic electron transport. 1176 70

Two operons have been cloned from Anabaena sp. strain PCC 7120 DNA, each of which encodes the three core subunits of distinct mitochondrial-type cytochrome c oxidases. The two operons are only 72 to 85% similar to one another at the nucleotide level in the most conserved subunit. One of these, coxBACII, is induced >20-fold in the middle to late stages of heterocyst differentiation. Analysis of green fluorescent protein reporters indicates that this operon is expressed specifically in proheterocysts and heterocysts. The other operon, coxBACI, is induced only 2.5-fold following nitrogen step-down and is expressed in all cells. Surprisingly, a disruption mutant of coxAII, the gene encoding subunit I of the heterocyst-specific oxidase, grows normally in the absence of combined nitrogen. It is likely that coxBACI and/or two other putative terminal oxidases present in the Anabaena sp. strain PCC 7120 genome are able to compensate for the loss of the heterocyst-specific oxidase in providing ATP for nitrogen fixation and maintaining a low oxygen level in heterocysts.
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PMID:Newly identified cytochrome c oxidase operon in the nitrogen-fixing cyanobacterium Anabaena sp. strain PCC 7120 specifically induced in heterocysts. 1194 64

The family of PII signal transduction proteins consists of one of the most highly conserved signalling proteins in nature. The cyanobacterial PII homologue transmits signals on the nitrogen and carbon status of the cells through phosphorylation of a seryl residue. Recently, we identified a protein phosphatase 2C (PP2C) homologue from the cyanobacterium Synechocystis PCC 6803, termed PphA, to be the cellular phospho-PII (PII-P) phosphatase. In this investigation, we characterized the enzymatic properties of PphA and investigated the regulation of its catalytic activity towards PII-P. PphA dephosphorylates phosphocasein and PII-P with similar efficiency in a strictly Mg2+- or Mn2+-dependent reaction. Low-molecular-weight phosphorylated molecules are poor substrates for PphA. Its reactivity towards PII-P, but not towards phosphocasein, is inhibited by various nucleotides, suggesting that this effect is based on specific properties of the PII protein. The inhibitory effect of ATP can be strongly enhanced by the addition of 2-oxoglutarate or oxaloacetate. At low concentrations of 2-oxoglutarate, changes in the ATP levels within the physiological range affect the degree of PII-Pase inhibition, whereas at 2-oxoglutarate levels beyond 0.1 mM, inhibition is almost complete at very low ATP levels. This suggests that PII dephosphorylation is not only sensitive to 2-oxoglutarate and oxaloacetate levels, it also integrates signals from the energy charge of the cells under specific cellular conditions.
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PMID:The novel protein phosphatase PphA from Synechocystis PCC 6803 controls dephosphorylation of the signalling protein PII. 1199 64

Vascular diseases like thrombosis, myocardial infarction, cerebral ischemia or chronic venous insufficiency affect a high proportion of the population. They are all associated with more or less pronounced ischemic conditions. We have previously shown that some venotropic drugs display an anti-ischemic activity, i.e. they prevent the hypoxia-induced decrease in ATP content in cultured cells. The effect is due to the fact that these molecules maintain mitochondrial respiratory activity during hypoxia. Among them is bilobalide. Starting from the 3D structure of bilobalide, we designed new molecules presenting the same chemical features. They were synthesized and tested for their biological activity. As the parent compound, two of them, malonic acid dicyclopent-2-enyl ester (MRC2P119) and 2-oxo-3-oxa-bicyclo[3.1.0]hexane-1-carboxylic acid allyl ester (MRC2P57), were able to markedly increase the respiratory control ratio of isolated mitochondria. They are able to prevent the inhibition of complex I by amytal and of complex III by myxothiazol, but not the uncoupling of the respiration by carbonylcyanide m-chlorophenyl hydrazone (m-CCP). Moreover, MRC2P119 and MRCP2P57 inhibit, in a dose-dependent way, the hypoxia-induced decrease in ATP content in endothelial cells as well as the subsequent activation of these cells as evidenced by an inhibition of the increase in neutrophil adherence to the endothelial cells induced by hypoxia. Finally, MRC2P119 prevent the hypoxia- and the hypoxia-reoxygenation-induced decrease in viability of SH-SY5Y neuroblastoma cells. In conclusion, we identified two new molecules, which display anti-ischemic properties when tested in vitro on endothelial and neuronal cell types. This anti-ischemic activity is probably due to a protection of complexes I and III of the mitochondrial respiratory chain.
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PMID:Mitochondrial respiratory chain as a new target for anti-ischemic molecules. 1200 18

Two ORFs, cphA and cphB, encoding proteins CphA and CphB with strong similarities to plant phytochromes and to the cyanobacterial phytochrome Cph1 of Synechocystis sp. PCC 6803 have been identified in the filamentous cyanobacterium Calothrix sp. PCC7601. While CphA carries a cysteine within a highly conserved amino-acid sequence motif, to which the chromophore phytochromobilin is covalently bound in plant phytochromes, in CphB this position is changed into a leucine. Both ORFs are followed by rcpA and rcpB genes encoding response regulator proteins similar to those known from the bacterial two-component signal transduction. In Calothrix, all four genes are expressed under white light irradiation conditions, albeit in low amounts. For heterologous expression and convenient purification, the cloned genes were furnished with His-tag encoding sequences at their 3' end and expressed in Escherichia coli. The two recombinant apoproteins CphA and CphB bound the chromophore phycocyanobilin (PCB) in a covalent and a noncovalent manner, respectively, and underwent photochromic absorption changes reminiscent of the P(r) and P(fr) forms (red and far-red absorbing forms, respectively) of the plant phytochromes and Cph1. A red shift in the absorption maxima of the CphB/PCB complex (lambda(max) = 685 and 735 nm for P(r) and P(fr), respectively) is indicative for a noncovalent incorporation of the chromophore (lambda(max) of P(r), P(fr) of CphA: 663, 700 nm). A CphB mutant generated at the chromophore-binding position (Leu246-->Cys) bound the chromophore covalently and showed absorption spectra very similar to its paralog CphA, indicating the noncovalent binding to be the only cause for the unexpected absorption properties of CphB. The kinetics of the light-induced P(fr) formation of the CphA-PCB chromoprotein, though similar to that of its ortholog from Synechocystis, showed differences in the kinetics of the P(fr) formation. The kinetics were not influenced by ATP (probing for autophosphorylation) or by the response regulator. In contrast, the light-induced kinetics of the CphB-PCB complex was markedly different, clearly due to the noncovalently bound chromophore.
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PMID:Two independent, light-sensing two-component systems in a filamentous cyanobacterium. 1204 74

Propionic acidemia (PA, MIM 232000 and 232050) is caused by a deficiency of mitochondrial biotin-dependent propionyl-CoA carboxylase (PCC, EC 6.4.1.3), a heteropolymeric enzyme composed of alpha and beta subunits, which are encoded by the PCCA and PCCB genes, respectively. The PCCA protein (alpha subunit) is responsible for the formation of carboxybiotin upon hydrolysis of ATP and contains a C-terminal biotin-binding domain and a biotin carboxylase domain, defined by homology with other biotin-dependent carboxylases, some of them characterized structurally. More than 24 mutations have been found in the PCCA gene in patients with PA, among them 14 missense mutations and one in-frame deletion, for which the precise molecular effect is unknown. In this study, we have established the pathogenicity of 11 PCCA mutations (10 missense and an in-frame deletion) by expression studies in deficient fibroblasts and in a cell-free in vitro system, and analyzed the effect of each mutation on PCC activity, protein stability and domain structure. The results show that most mutant proteins show an increased turnover and are functionally deficient, suggesting that the structural alterations they cause are incompatible with normal assembly to produce a stable, functional PCC oligomer. These results are discussed in the context of the genotype-phenotype correlations in PCCA-deficient PA patients.
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PMID:Functional characterization of PCCA mutations causing propionic acidemia. 1238 75


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