Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.55 (PTR)
 433 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During this study, we analysed the pericentric inversion that distinguishes human chromosome 12 (HSA12) from the homologous chimpanzee chromosome (PTR10). Two large chimpanzee-specific duplications of 86 and 23 kb were observed in the breakpoint regions, which most probably occurred associated with the inversion. The inversion break in PTR10p caused the disruption of the SLCO1B3 gene in exon 11. However, the 86-kb duplication includes the functional SLCO1B3 locus, which is thus retained in the chimpanzee, although inverted to PTR10q. The second duplication spans 23 kb and does not contain expressed sequences. Eleven genes map to a region of about 1 Mb around the breakpoints. Six of these eleven genes are not among the differentially expressed genes as determined previously by comparing the human and chimpanzee transcriptome of fibroblast cell lines, blood leukocytes, liver and brain samples. These findings imply that the inversion did not cause major expression differences of these genes. Comparative FISH analysis with BACs spanning the inversion breakpoints in PTR on metaphase chromosomes of gorilla (GGO) confirmed that the pericentric inversion of the chromosome 12 homologs in GGO and PTR have distinct breakpoints and that humans retain the ancestral arrangement. These findings coincide with the trend observed in hominoid karyotype evolution that humans have a karyotype close to an ancestral one, while African great apes present with more derived chromosome arrangements.
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PMID:Breakpoint analysis of the pericentric inversion between chimpanzee chromosome 10 and the homologous chromosome 12 in humans. 1554 20

SS, a natural cyclic tetradecapeptide, is a potent suppressor of pituitary GH and TSH secretion. At least five distinct SS receptor (SSTR) subtypes have been cloned and termed SSTRs 1-5. Both SSTR2 and SSTR5 regulate human GH and TSH secretion. Recently, a novel enzymatically stable SS analog, PTR-3173 (Somatoprim), with affinity for human SSTR2, SSTR4 and SSTR5, has been identified. This cyclic heptapeptide analog suppressed rat GH in vivo with no effect on insulin and minimal effect on glucagon secretion. Using primary cultures of human fetal pituitaries (20-24-week gestation) and GH-secreting adenomas, we studied the in vitro inhibitory effects of PTR-3173 on human pituitary secretion. PTR-3173 suppressed GH release from both fetal pituitaries (maximal suppression of 54% with 10 nM) and cultures of GH-cell adenomas (35% suppression with 100 nM). Octreotide and PTR-3173 had comparable inhibitory effects on GH secretion from fetal human pituitaries. TSH was mildly suppressed by PTR-3173, whereas ACTH secretion was not affected in fetal pituitary cultures. In cultures of eight GH-secreting adenomas, octreotide was superior to PTR-3173 in suppressing GH from two adenomas, PTR-3173 was more potent in three other tumors, and three adenomas did not respond significantly to either analog. PTR-3173 suppressed PRL in several mixed GH-PRL adenomas. In conclusion, PTR-3173, a novel SS analog with a unique SSTRs binding combination, is a potent in vitro suppressor of human GH. Combining this inhibitory effect with the lack of effect on insulin secretion, it is suggested that PTR-3173 may be clinically useful for the treatment of acromegaly.
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PMID:PTR-3173 (somatoprim), a novel somatostatin analog with affinity for somatostatin receptors 2, 4 and 5 is a potent inhibitor of human GH secretion. 1563 23

Recently, increased interest has focused on the diagnostic potential of volatile organic compounds (VOC) exhaled in human breath as this substance group has been conjectured in indoor air quality and disease screening. Proton transfer reaction-mass spectrometry (PTR-MS) has been established as a new tool for a rapid determination of exhaled air profile. However, no investigations have been carried out into the profile of exhaled air as determined by PTR-MS. Therefore, it was the aim of the present study to determine the profile of exhaled breath in a field survey enrolling 344 persons. Analysis was performed using PTR-MS. No significant correlations with age, blood pressure, and body mass index could be observed with any molecular mass. The present study delineates possible reference values for PTR-MS investigations into exhaled air profile. In conclusion, the present study was the first to delineate mass spectrometric characteristics of an average patient sample as possible reference values.
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PMID:Mass spectrometric profile of exhaled breath--field study by PTR-MS. 1570 43

In addition to the fusion of human chromosome 2, nine pericentric inversions are the most conspicuous karyotype differences between humans and chimpanzees. In this study we identified the breakpoint regions of the pericentric inversion of chimpanzee chromosome 11 (PTR 11) homologous to human chromosome 9 (HSA 9). The break in homology between PTR 11p and HSA 9p12 maps to pericentromeric segmental duplications, whereas the breakpoint region orthologous to 9q21.33 is located in intergenic single-copy sequences. Close to the inversion breakpoint in PTR 11q, large blocks of alpha satellites are located, which indicate the presence of the centromere. Since G-banding analysis and the comparative BAC analyses performed in this study imply that the inversion breaks occurred in the region homologous to HSA 9q21.33 and 9p12, but not within the centromere, the structure of PTR 11 cannot be explained by a single pericentric inversion. In addition to this pericentric inversion of PTR 11, further events like centromere repositioning or a second smaller inversion must be assumed to explain the structure of PTR 11 compared with HSA 9.
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PMID:Molecular characterization of the pericentric inversion of chimpanzee chromosome 11 homologous to human chromosome 9. 1582 Mar 5

A 1242 base pair DNA fragment from Bacillus halodurans H4 isolated from alkaline sediments of Lake Bogoria (Kenya) coding for a potential protease was cloned and sequenced. The hexa-histidine-tagged enzyme was overexpressed in Escherichia coli and was purified in one step by immobilized-metal affinity chromatography (IMAC) on Ni-NTA resin. The protease (ppBH4) presents an inverted zincin motif, HXXEH, which defines the inverzincin family. It shares several biochemical and molecular properties with the clan ME family M16 metallopeptidases (pitrilysins), as well as with database hypothetical proteins that are potential M16 family enzymes. Thus, like insulysin and nardilysin, but contrary to bacterial pitrilysin, ppBH4 is inactivated by sulfhydryl alkylating agents. On the other hand, like bacterial pitrilysin, ppBH4 is sensitive to reducing agents. The enzymatic activity of ppBH4 is limited to substrates smaller than proteins. In contrast to insulin, dynorphin and insulin B-chain are very good substrates for ppBH4 and several cleavage sites are common with those observed with well-characterized pitrilysins. As deduced from amino acid sequence, as well as determined by gel-filtration and SDS-polyacrylamide gel electrophoresis, ppBH4 is an active monomer of 46.5 kDa. This feature distinguishes ppBH4 from all other enzymes of the pitrilysin family so far described whose molecular masses range from 100 to 140 kDa.
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PMID:Cloning, expression and characterization of a 46.5-kDa metallopeptidase from Bacillus halodurans H4 sharing properties with the pitrilysin family. 1586 16

A T-DNA tagged mutant line of Arabidopsis thaliana, produced with a promoter trap vector carrying a promoterless gus (uidA) as a reporter gene, showed GUS induction in response to mechanical wounding. Cloning of the chromosomal DNA flanking the T-DNA revealed that the insert had caused a knockout mutation in a PTR-type peptide transporter gene named At5g46050 in GenBank, here renamed AtPTR3. The gene and the deduced protein were characterized by molecular modelling and bioinformatics. Molecular modelling of the protein with fold recognition identified 12 transmembrane spanning regions and a large loop between the sixth and seventh helices. The structure of AtPTR3 resembled the other PTR-type transporters of plants and transporters in the major facilitator superfamily. Computer analysis of the AtPTR3 promoter suggested its expression in roots, leaves and seeds, complex hormonal regulation and induction by abiotic and biotic stresses. The computer-based hypotheses were tested experimentally by exposing the mutant plants to amino acids and several stress treatments. The AtPTR3 gene was induced by the amino acids histidine, leucine and phenylalanine in cotyledons and lower leaves, whereas a strong induction was obtained in the whole plant upon exposure to salt. Furthermore, the germination frequency of the mutant line was reduced on salt-containing media, suggesting that the AtPTR3 protein is involved in stress tolerance in seeds during germination.
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PMID:Structural and functional characterization of AtPTR3, a stress-induced peptide transporter of Arabidopsis. 1588 94

Two novel metalloproteases from Arabidopsis thaliana, termed AtPrePI and AtPrePII, were recently identified and shown to degrade targeting peptides in mitochondria and chloroplasts using an ambiguous targeting peptide. AtPrePI and AtPrePII are classified as dually targeted proteins as they are targeted to both mitochondria and chloroplasts. Both proteases harbour an inverted metal binding motif and belong to the pitrilysin subfamily A. Here we have investigated the subsite specificity of AtPrePI and AtPrePII by studying their proteolytic activity against the mitochondrial F(1)beta pre-sequence, peptides derived from the F(1)beta pre-sequence as well as non-mitochondrial peptides and proteins. The degradation products were analysed, identified by MALDI-TOF spectrometry and superimposed on the 3D structure of the F(1)beta pre-sequence. AtPrePI and AtPrePII cleaved peptides that are in the range of 10 to 65 amino acid residues, whereas folded or longer unfolded peptides and small proteins were not degraded. Both proteases showed preference for basic amino acids in the P(1) position and small, uncharged amino acids or serine residues in the P'(1) position. Interestingly, both AtPrePI and AtPrePII cleaved almost exclusively towards the ends of the alpha-helical elements of the F(1)beta pre-sequence. However, AtPrePI showed a preference for the N-terminal amphiphilic alpha-helix and positively charged amino acid residues and degraded the F(1)beta pre-sequence into 10-16 amino acid fragments, whereas AtPrePII did not show any positional preference and degraded the F(1)beta pre-sequence into 10-23 amino acid fragments. In conclusion, despite the high sequence identity between AtPrePI and AtPrePII and similarities in cleavage specificities, cleavage site recognition differs for both proteases and is context and structure dependent.
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PMID:Two novel targeting peptide degrading proteases, PrePs, in mitochondria and chloroplasts, so similar and still different. 1589 67

Obesity is one of the most serious threats to human health today. Although there is general agreement that environmental factors such as diet have largely caused the current obesity pandemic, the environmental changes have not affected all individuals equally. To model gene-by-environment interactions in a mouse model system, our group has generated an F(16) advanced intercross line (AIL) from the SM/J and LG/J inbred strains. Half of our sample was fed a low-fat (15% energy from fat) diet while the other half was fed a high-fat (43% energy from fat) diet. The sample was assayed for a variety of obesity- and diabetes-related phenotypes such as growth rate, response to glucose challenge, organ and fat pad weights, and serum lipids and insulin. An examination in the F(16) sample of eight adiposity quantitative trait loci previously identified in an F(2) intercross of SM/J and LG/J mouse strains reveals locus-by-diet interactions for all previously mapped loci. Adip7, located on proximal chromosome 13, demonstrated the most interactions and therefore was selected for fine mapping with microsatellite markers. Three phenotypic traits, liver weight in male animals, serum insulin in male animals, and reproductive fat pad weight, show locus-by-diet interactions in the 127-kb region between markers D13Mit1 and D13Mit302. The phosphofructokinase (PFK) C (Pfkp) and the pitrilysin metalloprotease 1 (Pitrm1) genes are compelling positional candidate genes in this region that show coding sequence differences between the parental strains in functional domains.
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PMID:Fine-mapping gene-by-diet interactions on chromosome 13 in a LG/J x SM/J murine model of obesity. 1591 10

Interest in on-line measurements of volatile organic compounds (VOCs) is increasing, as sensitive, compact, and affordable direct inlet mass spectrometers are becoming available. Proton-transfer reaction mass spectrometry (PTR-MS) distinguishes itself by its high sensitivity (low ppt range), high time resolution (200 ms), little ionization-induced fragmentation, and ionization efficiency independent of the compound to be analyzed. Yet, PTR-MS has a shortcoming. It is a one-dimensional technique that characterizes compounds only via their mass, which is not sufficient for positive identification. Here, we introduce a technical and analytical extension of PTR-MS, which removes this shortcoming, while preserving its salient and unique features. Combining separation of VOCs by gas chromatography (GC) with simultaneous and parallel detection of the GC effluent by PTR-MS and electron impact MS, an unambiguous interpretation of complex PTR-MS spectra becomes feasible. This novel development is discussed on the basis of characteristic performance parameters, such as resolution, linear range, and detection limit. The recently developed drift tube with a reduced reaction volume is crucial to exploit the full potential of the setup. We illustrate the performance of the novel setup by analyzing a complex food system.
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PMID:Unambiguous identification of volatile organic compounds by proton-transfer reaction mass spectrometry coupled with GC/MS. 1598 17

To characterize the flavor of liquid whey, 11 samples of whey representing a wide range of types were sourced from cheese and casein-making procedures, either industrial or from pilot-plant facilities. Whey samples were assessed for flavor by descriptive sensory evaluation and analyzed for headspace volatile composition by proton transfer reaction-mass spectrometry (PTR-MS). The sensory data clearly distinguished between the samples in relation to the processes of manufacture; that is, significant differences were apparent between cheese, rennet, and acid wheys. For Mozzarella and Quarg wheys, in which fermentation progressed to low pH values, the starter cultures used for cheese making had a significant influence on flavor. In comparison, Cheddar and Gouda wheys were described by milk-like flavors, and rennet casein wheys were described by "sweet" (oat-like and "sweet") and thermally induced flavors. The volatile compound data obtained by PTR-MS differentiated the samples as distinctive and reproducible "chemical fingerprints". On applying partial least squares regression to determine relationships between sensory and volatile composition data, sensory characteristics such as "rancid" and cheese-like odors and "caramelized milk," yogurt-like, "sweet," and oat-like flavors were found to be related to the presence and absence of specific volatile compounds.
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PMID:Sensory characteristics and related volatile flavor compound profiles of different types of whey. 1602 81


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