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At least 973 records · Page 54Linked to original sources
PubMed2005

Identification and characterization of Sulfolobus solfataricus D-gluconate dehydratase: a key enzyme in the non-phosphorylated Entner-Doudoroff pathway.

The extremely thermoacidophilic archaeon Sulfolobus solfataricus utilizes D-glucose as a sole carbon and energy source through the non-phosphorylated Entner-Doudoroff pathway. It has been suggested that this micro-organism metabolizes D-gluconate, the oxidized form of D-glucose, to pyruvate and D-glyceraldehyde by using two unique enzymes, D-gluconate dehydratase and 2-keto-3-deoxy-D-gluconate aldolase. In the present study, we report the purification and characterization of D-gluconate dehydratase from S. solfataricus, which catalyses the conversion of D-gluconate into 2-keto-3-deoxy-D-gluconate. D-Gluconate dehydratase was purified 400-fold from extracts of S. solfataricus by ammonium sulphate fractionation and chromatography on DEAE-Sepharose, Q-Sepharose, phenyl-Sepharose and Mono Q. The native protein showed a molecular mass of 350 kDa by gel filtration, whereas SDS/PAGE analysis provided a molecular mass of 44 kDa, indicating that D-gluconate dehydratase is an octameric protein. The enzyme showed maximal activity at temperatures between 80 and 90 degrees C and pH values between 6.5 and 7.5, and a half-life of 40 min at 100 degrees C. Bivalent metal ions such as Co2+, Mg2+, Mn2+ and Ni2+ activated, whereas EDTA inhibited the enzyme. A metal analysis of the purified protein revealed the presence of one Co2+ ion per enzyme monomer. Of the 22 aldonic acids tested, only D-gluconate served as a substrate, with K(m)=0.45 mM and V(max)=0.15 unit/mg of enzyme. From N-terminal sequences of the purified enzyme, it was found that the gene product of SSO3198 in the S. solfataricus genome database corresponded to D-gluconate dehydratase (gnaD). We also found that the D-gluconate dehydratase of S. solfataricus is a phosphoprotein and that its catalytic activity is regulated by a phosphorylation-dephosphorylation mechanism. This is the first report on biochemical and genetic characterization of D-gluconate dehydratase involved in the non-phosphorylated Entner-Doudoroff pathway.

Amino Acid Sequence↗
PubMed2005

The myo-inositol-1-phosphate synthase gene is essential in Trypanosoma brucei.

The de novo synthesis of myo-inositol occurs via a two-step process: first, glucose 6-phosphate is converted into inositol 1-phosphate by an INO1 (myo-inositol-1-phosphate synthase; EC 5.5.1.4); then, it is dephosphorylated by an inositol monophosphatase. The myo-inositol can then be incorporated into PI (phosphatidylinositol), which is utilized in a variety of cellular functions, including the biosynthesis of GPI (glycosylphosphatidylinositol) anchors. A putative INO1 was identified in the Trypanosoma brucei genome database and, by recombinant expression in Escherichia coli, was shown to be a catalytically active INO1. To investigate the importance of INO1, we created a conditional knockout, which, under non-permissive conditions, showed that INO1 is an essential gene in bloodstream form T. brucei and that the de novo synthesized myo-inositol is used for the formation of PI and GPI anchors.

Animals↗
PubMedDate not supplied

Molecular identification and characterization of rat Abcc1 cDNA: existence of two splicing variants and species difference in drug-resistance profile.

The human ABCC1 gene, a member of the ATP-binding cassette transporter super-family, plays a critical role in conferring cancer cell resistance to chemotherapeutic drugs. In the present study, we have cloned the full-length cDNA of rat Abcc1 and evaluated its significance in drug resistance. Analysis using the currently available genome database revealed that the rat Abcc1 gene is located on rat chromosome 13 and consists of at least 30 exons. The rat Abcc1 cDNA cloned from the spleen was 4981-bp long, within which two additional splicing variants were discovered. The rat Abcc1 gene is expressed in a wide variety of organs, with the highest expression being observed in the spleen. Human embryonic kidney 293 cells were transfected with the rat Abcc1/pcDNA3.1 vector to stably express rat Abcc1. Overexpression of rat Abcc1 elicited high resistance to etoposide. In contrast to the hitherto known drug-resistance profile of human ABCC1, rat Abcc1 did not significantly confer cellular resistance to anthracyclins or Vinca alkaloids. Our results strongly suggest that there is a significant species difference between human ABCC1 and rat Abcc1 in their contribution to the drug-resistance profile.

Amino Acid Sequence↗
PubMed2002

Identification and characterization of tRNA (Gm18) methyltransferase from Thermus thermophilus HB8: domain structure and conserved amino acid sequence motifs.

BACKGROUND: Transfer RNAs from an extreme thermophile, Thermus thermophilus, commonly possess 2'-O-methylguanosine at position 18 (Gm18) in the D-loop. This modification is post-transcriptionally introduced by tRNA (Gm18) methyltransferase. RESULTS: Partial amino acid sequence data were obtained from purified T. thermophilus tRNA (Gm18) methyltransferase by peptide sequencing and mass spectrometry. The sequence data were used to screen the T. thermophilus genome database currently in progress, resulting in the identification of the corresponding gene. Purified recombinant enzyme showed a strict specificity for methylation at the 2'-OH of G18 in tRNA. Sequence alignment with other known or putative methyltransferases elucidates that tRNA (Gm18) methyltransferases have specific conserved region as well as three consensus motifs found in RNA ribose 2'-O-methyltransferases. The enzyme truncated at its N and C termini by limited tryptic digestion still retained binding activity for S-adenosyl-l-homocysteine, but lost the catalytic activity. CONCLUSION: This is the first report describing the identification of a methyltransferase gene of the trmH family through the analysis of a purified protein. Further, our results indicate that a restricted region(s) in the terminal amino acid residues of T. thermophilus tRNA (Gm18) methyltransferase are responsible for tRNA recognition and a main part of the enzyme is allocated for a catalytic core.

Amino Acid Motifs↗
PubMed2003

Molecular analysis of the serine/threonine kinase Akt and its expression in the mosquito Aedes aegypti.

A key component of the insulin-signalling pathway, the protein kinase Akt, was identified and cloned as a cDNA from ovaries of the mosquito Aedes aegypti. An ortholog gene was found in the Anopheles gambiae genome database, and like other Akts, both mosquito Akts possess pleckstrin homology domains for membrane binding and a serine/threonine kinase domain. When Ae. aegypti ovaries were treated with bovine insulin in vitro, a putative Akt was threonine-phosphorylated, as expected for Akts. AaegAKT was only expressed in embryos for the first 6 h after oviposition and in ovaries before and during a gonotrophic cycle.

Aedes↗
PubMed2003

Transcriptome analysis of the cowpea weevil bruchid: identification of putative proteinases and alpha-amylases associated with food breakdown.

We describe here the first systematic work to discover insect genes involved in food breakdown using a cDNA library enriched for gut-expressed transcripts from Callosobruchus maculatus. A total of 1056 clones were screened for cDNA insert-containing plasmids, and 503 nonredundant open reading frames were discovered. Twenty-three inferred genes potentially involved in digestive processes in cowpea weevil were identified, including proteinases and amylases. The predicted catalytic sites were identified in the inferred cysteine and aspartic acid proteinases, and in alpha-amylases. Transcriptome analysis of the cowpea bruchid will potentially permit gene discovery in other beetles, an insect order of major economic and ecological importance that is poorly represented in genomic databases.

Amino Acid Sequence↗
PubMed2000

Phosphorylcholine decoration of lipopolysaccharide differentiates commensal Neisseriae from pathogenic strains: identification of licA-type genes in commensal Neisseriae.

Phosphorylcholine (ChoP) is a potential candidate for a plurispecific vaccine, because it is present on surface components of many mucosal organisms, including Haemophilus influenzae, Streptococcus pneumoniae and Pseudomonas aeruginosa. In addition, ChoP has been detected on pili of Neisseria meningitidis and Neisseria gonorrhoeae. In this study, we demonstrate the presence of the phosphorylcholine epitope on the lipopolysaccharides (LPSs) of several species of commensal Neisseriae (Cn), a property that differentiates commensal from the pathogenic strains of Neisseriae. In an extended survey of 78 strains, we confirmed the exclusive expression of the ChoP epitope on pili of pathogenic Neisseriae. Despite the presence of pili on Cn, which are homologous to Class II pili of N. meningitidis, they did not react with anti-ChoP antibody. This observation was further supported by the fact that 14C-labelled choline was incorporated only in the LPSs of Cn. Analysis of the LPS of N. lactamica strain NL4 revealed two distinct and interconvertible molecular species of LPS with high and low levels of reactivity with anti-ChoP antibody. In addition, on/off phase variation gave rise to frequent modulation in the levels of antibody reactivity. A concurrent modulation was also observed in the binding of C-reactive protein, CRP, a ChoP-binding reactant that is implicated in bacterial clearance. Genetic analysis showed the presence of a gene in several Cn spp. with significant sequence identity to H. influenzae licA. This gene encodes choline kinase and is also involved in phase variation of the LPS-associated ChoP in H. influenzae. In contrast, licA-like genes were not identified in the pathogenic Neisseria strains tested. They are absent from N. meningitidis strain Z2491 genome database. These data suggest that the genetic basis for ChoP incorporation in Cn LPS resembles that in H. influenzae spp. and may be distinct from that generating the ChoP epitope on pili of pathogenic Neisseriae. Further, the modulation of ChoP expression on Cn LPS, and corresponding modulation of CRP binding, has the potential to confer the property of immune avoidance and thus of persistence on mucosa.

Amino Acid Sequence↗
PubMed2002

A novel Myb-related protein involved in transcriptional activation of encystation genes in Giardia lamblia.

Giardia lamblia is an important human intestinal parasite that survives outside of the host by differentiation of trophozoites into infectious cysts. Transcriptional regulation is key for encystation gene expression, but the mechanisms are unknown. Giardia genome database searches identified a myb-like gene (gmyb2) whose expression increased during encystation. Epitope-tagged gMyb2 localized to both nuclei. DNA binding and mutation analysis showed that gMyb2 binds specifically to C(T/A)ACAG, a c-Myb-like target sequence in the promoters of encystation-induced genes encoding gMyb2, three cyst wall proteins and G6PI-B, a key enzyme in cyst wall polysaccharide biosynthesis. gMyb2 binding sites were not found in the upstream regions of 31 other giardial genes. Deletion of the putative gMyb2 binding site greatly reduced encystation-specific promoter activity of g6pi-b. Fusion of gMyb2 binding sites to the constitutive ran promoter or g6pi-b promoter deletion lacking the gMyb2 binding site in-duced encystation-specific expression. gMyb2 may play an important role in transcriptional regulation of encystation genes, and may help co-ordinate synthesis of cyst wall proteins and polysaccharide. gMyb2 is the first giardial transcription factor to be functionally identified and the first that is associated with upregulation of encystation genes. This work provides a model for study of differential gene regulation in early diverging eukaryotic organisms.

5' Flanking Region↗
PubMed2000

Molecular cloning, functional expression and characterisation of RCC reductase involved in chlorophyll catabolism.

Red chlorophyll catabolite (RCC) reductase (RCCR) and pheophorbide (Pheide) a oxygenase (PaO) catalyse the key reaction of chlorophyll catabolism, porphyrin macrocycle cleavage of Pheide a to a primary fluorescent catabolite (pFCC). RCCR was purified from barley and a partial gene sequence was cloned (pHvRCCR). The gene was expressed at all stages of leaf development and in roots. By comparison with different databases, genomic sequences and expressed sequence tags similar to RCCR were found in phylogenetically diverse species, and activity of RCCR was demonstrated in two of them, Arabidopsis thaliana and Marchantia polymorpha. The gene of A. thaliana (AtRCCR) was employed for molecular cloning, heterologous expression and the production of polyclonal antibodies. With recombinant RCCR, the major product of RCC reduction was pFCC-1, but small quantities of its C1 epimer, pFCC-2, also accumulated. The reaction required reduced ferredoxin and was sensitive to oxygen. AtRCCR encoded a 35 kDa protein which was used for chloroplast import experiments. Upon transport, it was processed to a mature form of 31 kDa. The significance of cloning of RCCR is discussed in respect to the evolution of chlorophyll catabolism and to the cloning of PaO.

Amino Acid Sequence↗
PubMed2000

Molecular organization, expression and chromosomal localization of the mouse pronapsin gene.

Napsins have been identified only very recently as new aspartic proteinases of the pepsin family. Isolation, sequencing and functional analysis of the mouse genomic locus indicates that the organization of the pronapsin gene into nine exons is identical to that of other mammalian aspartic proteinase precursors, including pepsinogen. However, the additional C-terminal residues, which are a distinguishing feature of napsins, are encoded within exon 9 and not within an additional exon. Quantitation of pronapsin mRNA using RT-PCR indicates that the gene is transcribed in lung, kidney and spleen but not in heart. Regulation of gene expression was not influenced by the extent of CpG methylation but depended on the recognition of potential binding motifs in the promoter region by specific transcription factors such as YY-1. The single copy of the mouse pronapsin gene was located on chromosome 7. In humans, there are two pronapsin genes and, based on the mouse information, preliminary structures were deduced for these from sequences in the human genome databases. They appear to be located together on chromosome 19.

Amino Acid Sequence↗
PubMed2002

Identification and characterization of thioredoxin and thioredoxin reductase from Aeropyrum pernix K1.

We have identified and characterized a thermostable thioredoxin system in the aerobic hyperthermophilic archaeon Aeropyrum pernix K1. The gene (Accession no. APE0641) of A. pernix encoding a 37 kDa protein contains a redox active site motif (CPHC) but its N-terminal extension region (about 200 residues) shows no homology within the genome database. A second gene (Accession no. APE1061) has high homology to thioredoxin reductase and encodes a 37 kDa protein with the active site motif (CSVC), and binding sites for FAD and NADPH. We cloned the two genes and expressed both proteins in E. coli. It was observed that the recombinant proteins could act as an NADPH-dependent protein disulfide reductase system in the insulin reduction. In addition, the APE0641 protein and thioredoxin reductase from E. coli could also catalyze the disulfide reduction. These indicated that APE1061 and APE0641 express thioredoxin (ApTrx) and thioredoxin reductase (ApTR) of A. pernix, respectively. ApTR is expressed as an active homodimeric flavoprotein in the E. coli system. The optimum temperature was above 90 degrees C, and the half-life of heat inactivation was about 4 min at 110 degrees C. The heat stability of ApTR was enhanced in the presence of excess FAD. ApTR could reduce both thioredoxins from A. pernix and E. coli and showed a similar molar specific activity for both proteins. The standard state redox potential of ApTrx was about -262 mV, which was slightly higher than that of Trx from E. coli (-270 mV). These results indicate that a lower redox potential of thioredoxin is not necessary for keeping catalytic disulfide bonds reduced and thereby coping with oxidative stress in an aerobic hyperthermophilic archaea. Furthermore, the thioredoxin system of aerobic hyperthermophilic archaea is biochemically close to that of the bacteria.

Amino Acid Motifs↗
PubMed1999

Pregnenolone esterification in Saccharomyces cerevisiae. A potential detoxification mechanism.

While studying the effect of steroids on the growth of the yeast Saccharomyces cerevisiae, we found that pregnenolone was converted into the acetate ester. This reaction was identified as a transfer of the acetyl group from acetyl-CoA to the 3beta-hydroxyl group of pregnenolone. The corresponding enzyme, acetyl-CoA:pregnenolone acetyltransferase (APAT) is specific for Delta5- or Delta4-3beta-hydroxysteroids and short-chain acyl-CoAs. The apparent Km for pregnenolone is approximately 0.5 microm. The protein associated with APAT activity was partially purified and finally isolated from an SDS/polyacrylamide gel. Tryptic peptides were generated and N-terminally sequenced. Two peptide sequences allowed the identification of an open reading frame (YGR177c, in the S. cerevisiae genome database) translating into a 62-kDa protein of hitherto unknown function. This protein encoded by a gene known as ATF2 displays 37% identity with an alcohol acetyltransferase encoded by the yeast gene ATF1. Disruption of ATF2 led to the complete elimination of APAT activity and consequently abolished the esterification of pregnenolone. In addition, a toxic effect of pregnenolone linked to the disruption of ATF2 was observed. Pregnenolone toxicity is more pronounced when the atf2-Delta mutation is introduced in a yeast strain devoid of the ATP-binding cassette transporters, PDR5 and SNQ2. Our results suggest that Atf2p (APAT) plays an active role in the detoxification of 3beta-hydroxysteroids in association with the efflux pumps Pdr5p and Snq2p.

ATP-Binding Cassette Transporters↗
PubMed1999

Identification of subunit g of yeast mitochondrial F1F0-ATP synthase, a protein required for maximal activity of cytochrome c oxidase.

By means of a yeast genome database search, we have identified an open reading frame located on chromosome XVI of Saccharomyces cerevisiae that encodes a protein with 53% amino acid similarity to the 11.3-kDa subunit g of bovine mitochondrial F1F0-ATP synthase. We have designated this ORF ATP20, and its product subunit g. A null mutant strain, constructed by insertion of the HIS3 gene into the coding region of ATP20, retained oxidative phosphorylation function. Assembly of F1F0-ATP synthase in the atp20-null strain was not affected in the absence of subunit g and levels of oligomycin-sensitive ATP hydrolase activity in mitochondria were normal. Immunoprecipitation of F1F0-ATP synthase from mitochondrial lysates prepared from atp20-null cells expressing a variant of subunit g with a hexahistidine motif indicated that this polypeptide was associated with other well-characterized subunits of the yeast complex. Whilst mitochondria isolated from the atp20-null strain had the same oxidative phosphorylation efficiency (ATP : O) as that of the control strain, the atp20-null strain displayed approximately a 30% reduction in both respiratory capacity and ATP synthetic rate. The absence of subunit g also reduced the activity of cytochrome c oxidase, and altered the kinetic control of this complex as demonstrated by experiments titrating ATP synthetic activity with cyanide. These results indicate that subunit g is associated with F1F0-ATP synthase and is required for maximal levels of respiration, ATP synthesis and cytochrome c oxidase activity in yeast.

Amino Acid Sequence↗
PubMed2002

A divergent gene family encoding candidate olfactory receptors of the moth Heliothis virescens.

The antennae of moths have been an invaluable model for studying the principles of odour perception. In spite of the enormous progress in understanding olfaction on the molecular level, for the moth one of the key elements in olfactory signalling, the odourant receptors, are still elusive. We have assessed a genome database of a heliothine moth (Heliothis virescens, Noctuidae) and employed exon-specific probes to screen an antennal cDNA library of this species. Analysis of isolated cDNA-clones led to the discovery of a divergent gene family encoding putative seven-transmembrane domain proteins. The notion that they may encode candidate olfactory receptors of the moth, was supported by a tissue-specific expression; several of the subtypes were exclusively expressed in antennae. By means of double-labelling in situ hybridization studies it was demonstrated that the receptors are indeed expressed in antennal sensory neurons; moreover, each receptor subtype appears to be expressed in a distinct population of sensory cells. The results strongly suggest that the newly discovered gene family indeed encodes olfactory receptors of moth.

Amino Acid Sequence↗
PubMedDate not supplied

Comparison of genome segments 2, 7 and 10 of bluetongue viruses serotype 2 for differentiation between field isolates and the vaccine strain.

Bluetongue (BT) virus serotype 2 (BTV 2) was first confirmed in Tunisia in February 2000 and has since spread northward and westward, infecting several other countries and islands, including Corsica, where clinical disease was reported in October 2000. BT was again reported on the Island in July 2001, some six months after a vaccination campaign against BTV 2. The molecular relationship between isolates of the BTV 2 Corsican wild-type viruses from 2000 and 2001, and the attenuated BTV 2 vaccine were determined by comparing corresponding sequences of genome segments 2, 7 and 10 with each other and with already published sequences available in the genome database. Complete genetic stability was observed between the isolates of the Corsican BTV 2. There was some divergence between the nucleotide sequences of segment 10 obtained from the wild-type and vaccine virus strains. Based on these differences, primers were selected that could be used in RT-PCR to differentiate between the wild-type and the vaccine viruses.

Amino Acid Sequence↗
PubMed2004

Functional reclassification of the putative cinnamyl alcohol dehydrogenase multigene family in Arabidopsis.

Of 17 genes annotated in the Arabidopsis genome database as cinnamyl alcohol dehydrogenase (CAD) homologues, an in silico analysis revealed that 8 genes were misannotated. Of the remaining nine, six were catalytically competent for NADPH-dependent reduction of p-coumaryl, caffeyl, coniferyl, 5-hydroxyconiferyl, and sinapyl aldehydes, whereas three displayed very low activity and only at very high substrate concentrations. Of the nine putative CADs, two (AtCAD5 and AtCAD4) had the highest activity and homology (approximately 83% similarity) relative to bona fide CADs from other species. AtCAD5 used all five substrates effectively, whereas AtCAD4 (of lower overall catalytic capacity) poorly used sinapyl aldehyde; the corresponding 270-fold decrease in k(enz) resulted from higher K(m) and lower k(cat) values, respectively. No CAD homologue displayed a specific requirement for sinapyl aldehyde, which was in direct contrast with unfounded claims for a so-called sinapyl alcohol dehydrogenase in angiosperms. AtCAD2, 3, as well as AtCAD7 and 8 (highest homology to sinapyl alcohol dehydrogenase) were catalytically less active overall by at least an order of magnitude, due to increased K(m) and lower k(cat) values. Accordingly, alternative and/or bifunctional metabolic roles of these proteins in plant defense cannot be ruled out. Comprehensive analyses of lignified tissues of various Arabidopsis knockout mutants (for AtCAD5, 6, and 9) at different stages of growth/development indicated the presence of functionally redundant CAD metabolic networks. Moreover, disruption of AtCAD5 expression had only a small effect on either overall lignin amounts deposited, or on syringyl-guaiacyl compositions, despite being the most catalytically active form in vitro.

Alcohol Dehydrogenase↗
PubMed2004

Identification of candidate cancer-causing genes in mouse brain tumors by retroviral tagging.

Murine retroviruses may cause malignant tumors in mice by insertional mutagenesis of host genes. The use of retroviral tagging as a means of identifying cancer-causing genes has, however, almost entirely been restricted to hematopoietic tumors. The aim of this study was to develop a system allowing for the retroviral tagging of candidate genes in malignant brain tumors. Mouse gliomas were induced by a recombinant Moloney murine leukemia virus encoding platelet-derived growth factor (PDGF) B-chain. The underlying idea was that tumors evolve through a combination of PDGF-mediated autocrine growth stimulation and insertional mutagenesis of genes that cooperate with PDGF in gliomagenesis. Common insertion sites (loci that were tagged in more than one tumor) were identified by cloning and sequencing retroviral flanking segments, followed by blast searches of mouse genome databases. A number of candidate brain tumor loci (Btls) were identified. Several of these Btls correspond to known tumor-causing genes; these findings strongly support the underlying idea of our experimental approach. Other Btls harbor genes with a hitherto unproven role in transformation or oncogenesis. Our findings indicate that retroviral tagging with a growth factor-encoding virus may be a powerful means of identifying candidate tumor-causing genes in nonhematopoietic tumors.

Animals↗
PubMed2004

Activating calcium-sensing receptor mutation in the mouse is associated with cataracts and ectopic calcification.

The extracellular calcium-sensing receptor (CaSR) plays a pivotal role in the regulation of extracellular calcium such that abnormalities, which result in a loss or gain of function, lead to hypercalcemia or hypocalcemia, respectively, in patients. Mice carrying CaSR knockout alleles develop hypercalcemia that mimics the disorders observed in humans. To date, there is no mouse model for an activating CaSR mutation. Here, we describe such a mouse model, named Nuf, originally identified for having opaque flecks in the nucleus of the lens in a screen for eye mutants. Nuf mice also display ectopic calcification, hypocalcemia, hyperphosphatemia, and inappropriately reduced levels of plasma parathyroid hormone. These features are similar to those observed in patients with autosomal dominant hypocalcemia. Inheritance studies of Nuf mice revealed that the trait was transmitted in an autosomal-dominant manner, and mapping studies located the locus to chromosome 16, in the vicinity of the CaSR gene (Mouse Genome Database symbol Gprc2a). DNA sequence analysis revealed the presence of a Gprc2a missense mutation, Leu723Gln. Transient expression of wild-type and mutant CaSRs in human embryonic kidney 293 cells demonstrated that the mutation resulted in a gain of function of the CaSR, which had a significantly lower EC(50). Thus, our results have identified a mouse model for an activating CaSR mutation, and the development of ectopic calcification and cataract formation, which tended to be milder in the heterozygote Nuf mice, indicates that an evaluation for such abnormalities in autosomal dominant hypocalcemia patients who have activating CaSR mutations is required.

Amino Acid Sequence↗