Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pregrowth hormone DNA was synthesized by polymerase chain reaction from a pituitary gland cDNA library of Baikal omul (Coregonus autumnalis Pallas). A cDNA was sequenced and found to encode a precursor protein of 210 amino acid residues, which included a putative signal peptide of 22 amino acid residues. Sequence comparison reveals close similarity of the omul growth hormone to those of other Salmoniformes species.
Mol Biol (Mosk)
PMID:[Primary structure of DNA, complementary for mRNA for the Baikal omul growth hormone]. 799 Aug 28

Porphobilinogen deaminase (PBG deaminase) is an early enzyme of the pathway for chlorophyll and heme synthesis. Using degenerate oligonucleotide primers, based on amino acid sequence data for purified PBG deaminase from pea, a fragment was amplified from Arabidopsis genomic DNA by PCR, and then used to isolate both a cDNA and a genomic clone for PBG deaminase from Arabidopsis. The cDNA, shown to be full-length by primer extension, encodes a precursor protein of 382 residues, which can be imported into isolated chloroplasts and processed to the mature size. The genomic clone encodes an identical sequence to the cDNA, except for the presence of four introns within the coding region of the mature protein, and 1.7 kb of upstream sequence. There is no obvious TATA box within 50 bp of the transcription start. Southern blot analysis suggests that PBG deaminase is encoded by a single gene in the Arabidopsis genome, and RNase protection experiments demonstrated that this gene is expressed in both leaves and roots. These results support the conclusion that there is only one form of PBG deaminase in all plant cells, which is located in the plastid.
Plant Mol Biol 1994 Nov
PMID:Porphobilinogen deaminase is encoded by a single gene in Arabidopsis thaliana and is targeted to the chloroplasts. 800

The human gastric bacterial pathogen Helicobacter pylori has been implicated in type B gastritis, peptic ulceration and gastric adenocarcinoma. Here we report on the cloning and genetic characterization of an H. pylori gene named vacA, which encodes the vacuolating cytotoxin VacA, a novel type of antigenic bacterial toxin that induces the formation of intracellular vacuoles in epithelial cells. The vacuolating cytotoxin activity is expressed by a subset of clinical isolates (Vac+), all of which produce the 87 kDa cytotoxin antigen, but strains which produce neither the activity nor the cytotoxin protein (Vac-) also carry the gene. Isogenic H. pylori mutants in vacA generated by transposon shuttle mutagenesis produce neither the VacA antigen nor a vacuolating activity in a cell culture model. The vacA gene itself encodes a precursor protein of 139.6 kDa consisting of a 33-amino acid signal sequence, the 87 kDa cytotoxin and a 50 kDa C-terminal domain with features typical of a bacterial outer membrane protein. The VacA precursor shows no significant primary sequence homology with any previously reported protein, but its structural organization closely resembles the IgA protease-type of exoprotein produced by pathogenic Neisseriae and Haemophilus species. Our current data support a model for secretion of the cytotoxin through the two bacterial membranes which involves the 50 kDa domain for outer membrane translocation with subsequent proteolytic cleavage and release of the mature 87 kDa cytotoxin into the extracellular environment.
Mol Microbiol 1994 Apr
PMID:Genetic analysis of the Helicobacter pylori vacuolating cytotoxin: structural similarities with the IgA protease type of exported protein. 805 55

The three-dimensional structure and disulfide connectivities of a 6-kDa protein isolated from the stigma of the ornamental tobacco Nicotiana alata has been determined by 1H NMR spectroscopy combined with simulated annealing calculations. The protein, termed C1, is a chymotrypsin inhibitor and is one of five homologous proteinase inhibitors that are proteolytically cleaved from a 40.3-kDa precursor protein. The other four proteinase inhibitors (T1 to T4) contain reactive sites for trypsin. The three-dimensional structure of C1 is generally well defined and contains a triple stranded beta-sheet as the dominant secondary structural feature. Several turns and a short region of 3(10) helix are also present. The putative chymotrypsin reactive site is present on an exposed loop which is less defined than the rest of the protein. The overall shape of C1 is disc-like and the N and C termini are exposed, supporting the proposal that this protein results from post-translational processing of the 40.3-kDa precursor protein.
J Mol Biol 1994 Sep 23
PMID:The three-dimensional solution structure by 1H NMR of a 6-kDa proteinase inhibitor isolated from the stigma of Nicotiana alata. 808 44

bfp, the structural gene of the major repeating bundle-forming pilus (BFP) subunit, was cloned from the enteroadherent factor (EAF) plasmid of enteropathogenic Escherichia coli (EPEC) strain B171 (O111:NM). The bfp open reading frame encoded a 193-amino-acid protein; comparison of this sequence with the biochemically determined N-terminal amino acid sequence showed that the mature pilin protein is comprised of 180 amino acids, that this sequence is similar to other members of the type IV pilin family, and that it is preceded by a 13-amino-acid signal peptide. Expression of the cloned bfp structural gene in an EPEC strain that had been cured of the EAF plasmid yielded a 21,000 dalton protein that co-migrated with the BFP precursor protein. Thus, other genes, probably carried by the EAF plasmid, are required for the maturation of the bfp product and for the production of extracellular pilus filaments. Use of bfp as a hybridization probe showed that homologous sequences are present in all tested EPEC strains and in 13 of 16 tested Salmonella serotypes. Fifty per cent of these bfp probe-sensitive salmonellae exhibited the localized-adherence (LA) phenotype when incubated with tissue culture cell monolayers, a trait previously associated with EAF plasmid-containing EPEC strains. Scanning electron micrographs of a bfp probe-sensitive, LA-positive Salmonella dublin strain showed that it grows as adherent colonies on infected monolayers and that within these colonies, BFP-like fibres form inter-bacterial linkages. For EAF plasmid-containing EPEC strains and for several Salmonella serotypes, BFP expression may lead to the development of adherent colonies on epithelial surfaces early in the infective process.
Mol Microbiol 1993 Feb
PMID:Cloning and characterization of the bundle-forming pilin gene of enteropathogenic Escherichia coli and its distribution in Salmonella serotypes. 809 20

Hordothionins (HTHs) are small anti-bacterial proteins present in barley endosperm which are processed from larger precursor proteins, consisting of an amino-terminal signal peptide (SP), the mature highly basic HTH and a carboxy-terminal acidic peptide (AP). Different HTH precursor proteins were expressed in tobacco to study the effects of the pre-sequences (SP) and pro-sequences (AP) on expression, processing, sorting and biological activity and hence the feasibility of engineering bacterial disease resistance into crops which lack these proteins. Maximum HTH expression levels of approximately 0.7% (11 mumol/kg) of total soluble protein in young tobacco leaves were obtained using a semi-synthetic gene construct encoding a complete chimaeric HTH precursor protein. Tenfold lower HTH expression levels (maximum 1.3 mumol/kg) were obtained using synthetic gene constructs without the AP-coding sequence and no expression was found in plants containing synthetic HTH gene constructs without SP- and AP-coding sequences. In both cases where expression was found, the precursors were apparently correctly processed, although the HTH produced in plants containing a construct without AP sequence appeared to be slightly modified. No effect on plant phenotype was observed. Localization studies indicated that the HTH was in identical fractions of plants expressing the two different precursors, albeit at a different ratio, and was not secreted into the intercellular spaces of leaves or culture medium by protoplasts. Our results indicated that the AP is not involved in sorting and suggested that it might facilitate transport through membranes. The in vitro toxicity of HTH isolated from transgenic tobacco plants expressing the two different precursor proteins for the bacterial plant pathogen Clavibacter michiganensis subsp. michiganensis appeared similar to that of the HTH purified from barley endosperm.
Plant Mol Biol 1994 Jan
PMID:Expression of biologically active hordothionins in tobacco. Effects of pre- and pro-sequences at the amino and carboxyl termini of the hordothionin precursor on mature protein expression and sorting. 811 Oct 29

Protein import into chloroplasts requires the movement of a precursor protein across the envelope membranes. The conformation of a precursor as it passes from the aqueous medium across the hydrophobic membranes is not known in detail. To address this problem we examined precursor conformation during translocation using the chimeric precursor PCDHFR, which contains the plastocyanin (PC) transit peptide in front of mouse cytosolic dihydrofolate reductase (DHFR). The chimeric protein is targeted to chloroplasts and is competent for import. The conformation of PCDHFR can be stabilized by complexing with methotrexate, an analogue of the substrate of DHFR. Methotrexate strongly inhibits DHFR import into yeast mitochondria (M. Eilers and G. Schatz, Nature 322 (1986) 228-232), presumably because the precursor must unfold to cross the membrane and it cannot do so when complexed with methotrexate. We show here that methotrexate does not block PCDHFR import into chloroplasts. Methotrexate does slow the rate of import, and protects DHFR from degradation once inside chloroplasts. The processed protein is localized in the stroma, indicating that import into thylakoids is impeded. Protease sensitivity assays indicate that the complex of precursor protein with methotrexate changes in conformation during the translocation across the envelope.
Plant Mol Biol 1994 Jan
PMID:Methotrexate does not block import of a DHFR fusion protein into chloroplasts. 811 Oct 32

A cDNA encoding the complete precursor of the phosphate translocator of the chloroplast inner envelope membrane has been isolated from a tobacco leaf (Nicotiana tabacum cv. Samsun) lambda gt 11 library. The tobacco cDNA is 1546 bp in length and encodes a precursor protein of 401 amino acid residues with a deduced molecular weight of 43705. A putative processing site between Ala-73 and Ala-74 of the precursor protein is suggested by comparison with the N-terminal sequences of the pea and spinach proteins. Removal of the transit peptide produces the mature protein of 328 amino acid residues with a molecular weight of 36038. Southern blot analysis suggests there is probably one copy of the phosphate translocator gene in the pea haploid genome and two copies in the tobacco haploid genome, one derived from each ancestral parental genome. Messenger RNAs essentially equivalent in size to the cDNAs (approx. 1.6 kb) were detected in extracts of all organs examined from tobacco and pea, including leaves, stems, sepals, petals, seed-pods, tendrils and roots. An immunochemically related protein of a similar size to the phosphate translocator was detected in the equivalent pea organs. The levels of both mRNA and protein in non-photosynthetic organs were lower than those in photosynthetic organs. Tobacco phosphate translocator mRNA was present at high levels in etiolated tissue and did not increase significantly after 24 h illumination. Germination and growth of tobacco seedlings in the presence of sucrose caused a 3.3-fold decrease in the level of the phosphate translocator mRNA.
Mol Gen Genet 1994 Mar
PMID:Expression of genes encoding the tobacco chloroplast phosphate translocator is not light-regulated and is repressed by sucrose. 812 15

To better characterize the activation products of factor B which are generated under physiologic conditions Ba was purified directly from human EDTA-plasma by immunoaffinity chromatography using anti-Ba Sepharose. SDS-PAGE analysis revealed the existence of degradation products of the Ba fragment which were truncated at the carboxyterminus. A monoclonal antibody (mAb D22/3) was produced by immunizing mice with a synthetic peptide which corresponds to the Ba carboxyterminus (Glu215-Arg234). This mAb was found to react with an epitope (Ba neo-epitope), which is newly formed after the generation of Ba from its precursor protein factor B. This neoantigenic determinant is absent both in factor B and the desArg/Lys Ba derivatives. The conversion of Ba by carboxypeptidases in human serum was monitored using an assay which is based on mAb D22/3, revealing a half-life of Ba in serum of 150 min. Furthermore, this assay allowed to quantitate plasma levels of intact and degraded Ba in healthy probands and in patients with chronic renal failure. The processing of the Ba carboxyterminus may be of functional relevance as the biological activity of the Ba fragment which had been shown to suppress human B lymphocyte functions in vitro resides in its carboxyterminal amino acid sequence.
Mol Immunol 1994 Mar
PMID:Characterization of physiologic breakdown products of the complement fragment Ba. 813 84

The final two steps in the biosynthesis of alpha-amidated bioactive peptides are catalyzed by peptidylglycine alpha-hydroxylating monooxygenase (PHM; EC 1.14.17.3) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL; EC 4.3.2.5). These enzymes are derived from the bifunctional precursor protein, peptidylglycine alpha-amidating monooxygenase. Because PHM is rate-limiting in peptide amidation and is copper-dependent, we examined the consequences of in vivo treatments with the copper-chelating drug disulfiram (Antabuse) on levels of alpha-amidated peptides and expression of PHM and PAL. Decreases in two amidated peptides (alpha-melanotropin and cholecystokinin) after disulfiram treatment were extremely pronounced outside the blood-brain barrier, with moderate decreases in the central nervous system. Unexpectedly, when assayed under optimal conditions in vitro, PHM activity was increased by disulfiram treatment, whereas PAL activity was unaltered. The increase in PHM activity in pituitary and atrium occurred within a few hours after the start of disulfiram treatment and was sustained up to 2 weeks after the cessation of treatment, whereas levels of alpha-amidated peptides remained low. Northern and Western blot analyses demonstrated that disulfiram had no influence on levels of peptidylglycine alpha-amidating monooxygenase mRNA or protein. Thus, inhibition of alpha-amidation by disulfiram in vivo occurs despite an increased Vmax of PHM assayed in vitro. The increase in PHM activity may result from induction of a physiologic mechanism that normally regulates this rate-limiting enzyme.
Mol Pharmacol 1993 Nov
PMID:Peptide alpha-amidation and peptidylglycine alpha-hydroxylating monooxygenase: control by disulfiram. 824 21


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