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)

Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by a partial porphobilinogen (PBG) deaminase deficiency. An exon-by-exon denaturing gradient gel electrophoresis (DGGE) analysis followed by direct sequencing of the DNA fragments was performed to investigate molecular defect in 8 unrelated patients living in south of France: one Algerian, two Moroccan and five French patients. We have optimized the DGGE method in order to study at the same time the fifteen exons of the PBG deaminase gene in only one electrophoresis run. Six different mutations were detected by abnormal mobility patterns. After characterization, a C insertion (716 ins C), 2 deletions (589 del 17 bp; 730 del CT), a non-sense mutation (R149X) and 2 missense mutations (A270G; R173W) were found. The R173W missense mutation was found in 3 unrelated patients, and 716 ins C, 589 del 17 bp and A270G were newly described. According to this small AIP samples, sensitivity of the DGGE screening method was 100%.
Cell Mol Biol (Noisy-le-grand) 1997 Feb
PMID:Acute intermittent porphyria: rapid molecular diagnosis. 907 87

Double-stranded (ds) RNA-specific adenosine deaminase converts adenosine residues into inosines in dsRNA and edits transcripts of certain cellular and viral genes such as glutamate receptor (GluR) subunits and hepatitis delta antigen. The first member of this type of deaminase, DRADA1, has been recently cloned based on the amino acid sequence information derived from biochemically purified proteins. Our search for DRADA1-like genes through expressed sequence tag databases led to the cloning of the second member of this class of enzyme, DRADA2, which has a high degree of sequence homology to DRADA1 yet exhibits a distinctive RNA editing site selectivity. There are four differentially spliced isoforms of human DRADA2. These different isoforms of recombinant DRADA2 proteins, including one which is a human homolog of the recently reported rat RED1, were analyzed in vitro for their GluR B subunit (GluR-B) RNA editing site selectivity. As originally reported for rat RED1, the DRADA2a and -2b isoforms edit GluR-B RNA efficiently at the so-called Q/R site, whereas DRADA1 barely edits this site. In contrast, the R/G site of GluR-B RNA was edited efficiently by the DRADA2a and -2b isoforms as well as DRADA1. Isoforms DRADA2c and -2d, which have a distinctive truncated shorter C-terminal structure, displayed weak adenosine-to-inosine conversion activity but no editing activity tested at three known sites of GluR-B RNA. The possible role of these DRADA2c and -2d isoforms in the regulatory mechanism of RNA editing is discussed.
Mol Cell Biol 1997 May
PMID:Editing of glutamate receptor B subunit ion channel RNAs by four alternatively spliced DRADA2 double-stranded RNA adenosine deaminases. 911 10

The apparent size (87.5 kDa) of the major polypeptide in freshly isolated chicken muscle AMP deaminase (AMPD.M) was comparable with that predicted from the sequences of the genes for the major muscle isoforms from human and rat. The size of the subunit of AMP deaminase from chicken muscle is indistinguishable from that of the rabbit enzyme. The peptide profiles of cyanogen bromide digests of AMPD.M from chicken and rabbit share a 17-kDa fragment, representing approximately 20% of the intact subunits of these enzymes. The first 25 residues of these fragments are 88.5% identical; the rabbit and chicken segments are greater than 92% and 84% identical, respectively, to the sequences predicted for residues 310-335 for AMPD.M from human and rat. Polyclonal rabbit antisera directed against AMPD.M from chicken breast recognize the full-length AMPD.M polypeptides on immunoblots of extracts of both avian and rabbit muscle, including an antiserum from the rabbit in which the antibody was prepared. The 17-kDa fragments, derived by incomplete cleavage of highly conserved internal segments of the deaminase subunit, share epitopes involved in the autorecognition of rabbit AMPD.M by rabbit polyclonal antibodies directed against the avian AMPD.M.
Comp Biochem Physiol B Biochem Mol Biol 1997 Mar
PMID:AMP-deaminases from chicken and rabbit muscle: partial primary sequences of homologous 17-kDa CNBr fragments: autorecognition by rabbit anti-[chicken AMPD]. 911 97

The cell wall structure of Salmonella typhimurium has been studied for the first time during transit from free-living to parasitic lifestyles. Peptidoglycan of S. typhimurium proliferating within human epithelial cells contains a high proportion of previously unidentified muropeptides (5-10-fold higher than in extracellular bacteria). Amino acid and mass-spectrometry analyses showed that these new components consist of dimeric cross-linked muropeptides lacking one of the two disaccharide (N-acetyl-glucosamine-beta-(1-->4)-N-acetyl-muramic acid) molecules. This unique structure suggests an active role for an N-acetyl-muramyl-L-alanine-amidase in remodelling the peptidoglycan of intracellular S. typhimurium. Additional alterations observed included: (i) the absence of glycine-containing muropeptides; (ii) the increase in the relative proportion of muropeptides cross-linked by L(meso)-diaminopimelyl-D(meso)-diaminopimelic acid (L-D) peptide bridges; and, (iii) the decrease in the global cross-linkage of the macromolecule. The structural alterations observed in the peptidoglycan of intracellular bacteria do not produce loss of the cell envelope. These results show that intracellular residence of S. typhimurium within epithelial cells is accompanied by significant changes in the bacterial cell wall. Remodelling of peptidoglycan structure may constitute another sophisticated strategy of this pathogen for adapting to and colonizing the intracellular niche of eukaryotic cells.
Mol Microbiol 1997 Feb
PMID:Peptidoglycan structure of Salmonella typhimurium growing within cultured mammalian cells. 915 41

Biofilm formation on a polymer surface which involves initial attachment and accumulation in multilayered cell clusters (intercellular adhesion) is proposed to be the major pathogenicity factor in Staphylococcus epidermidis foreign-body-associated infections. We have characterized two distinct classes of biofilm-negative Tn917 mutants in S. epidermidis affected in initial attachment (class A) or intercellular adhesion (class B). mut1 (class A mutant) lacks five surface-associated proteins with molecular masses of 120, 60, 52, 45 and 38 kDa and could be complemented by transformation with a 16.4 kb wild-type DNA fragment. The complemented mutant was able to attach to a polystyrene surface, to form a biofilm, and produced all of the proteins missing from mut1. Subcloning experiments revealed that the 60 kDa protein is sufficient for initial attachment. Immunofluorescence microscopy using an antiserum raised against the 60 kDa protein showed that this protein is located at the cell surface. DNA-sequence analysis of the complementing region revealed a single open reading frame which consists of 4005 nucleotides and encodes a deduced protein of 1335 amino acids with a predicted molecular mass of 148kDa. The amino acid sequence exhibits a high similarity (61% identical amino acids) to the atl gene product of Staphylococcus aureus, which represents the major autolysin; therefore the open reading frame was designated atlE. By analogy with the S. aureus autolysin, AtlE is composed of two bacteriolytically active domains, a 60 kDa amidase and a 52 kDa glucosaminidase domain, generated by proteolytic processing. The 120 kDa protein missing from mut1 presumably represents the unprocessed amidase and glucosaminidase domain after proteolytic cleavage of the signal- and propeptide. The 45 and 38kDa proteins are probably the degradation products of the 60 and 52 kDa proteins, respectively. Additionally, AtlE was found to exhibit vitronectin-binding activity, indicating that AtlE plays a role in binding of the cells not only to a naked polystyrene surface during early stages of adherence, but also to plasma protein-coated polymer surfaces during later stages of adherence. Our findings provide evidence for a new function of an autolysin (AtlE) in mediating the attachment of bacterial cells to a polymer surface, representing the prerequisite for biofilm formation.
Mol Microbiol 1997 Jun
PMID:Evidence for autolysin-mediated primary attachment of Staphylococcus epidermidis to a polystyrene surface. 922 8

A previous study described an unusual influence of neutral salts on the behavior of trout muscle AMP-deaminase (AMPD) in its interactions with subcellular particulate matter (Lushchak and Storey 1994, Fish Physiol. Biochem. 13: 356-368). The present study shows that this behavior is also shared by the muscle enzyme of two other fish species, sea scorpion (Scorpaena porcus) and corb (Sciena umbra), indicating that this describes a principle for AMPD interaction with cellular particulate material. AMPD binding to particulate matter increased with increasing KCl concentration through the physiological range (100-200 mM), but at higher salt concentrations the amount of bound enzyme was reduced. The pattern of binding was not influenced by hydrophobic interactions since addition of the nonionic detergents, Triton X-100 or Tween-80, did not alter the distribution of bound versus free enzyme although both detergents, at low concentrations, enhanced enzyme maximal activity. AMPD binding to particulate matter was also influenced by pH, the amount of free enzyme rising by nearly 3-fold as pH fell within the physiological range from 7.5 to 6.5. It is concluded that neither electrostatic nor hydrophobic forces alone can account for the unusual solubilization of AMPD from fish muscle and it is possible that the effect is also related to ion-induced conformational changes in the structure of AMPD and/or of the myosin to which the enzyme binds.
Biochem Mol Biol Int 1997 Oct
PMID:Unusual AMP-deaminase solubilization from teleost fish white muscle. 935 87

We report, for the first time, the presence in Helicobacter pylori of an aliphatic amidase that, like urease, contributes to ammonia production. Aliphatic amidases are cytoplasmic acylamide amidohydrolases (EC 3.5.1.4) hydrolysing short-chain aliphatic amides to produce ammonia and the corresponding organic acid. The finding of an aliphatic amidase in H. pylori was unexpected as this enzyme has only previously been described in bacteria of environmental (soil or water) origin. The H. pylori amidase gene amiE (1017 bp) was sequenced, and the deduced amino acid sequence of AmiE (37746Da) is very similar (75% identity) to the other two sequenced aliphatic amidases, one from Pseudomonas aeruginosa and one from Rhodococcus sp. R312. Amidase activity was measured as the release of ammonia by sonicated crude extracts from H. pylori strains and from recombinant Escherichia coli strains overproducing the H. pylori amidase. The substrate specificity was analysed with crude extracts from H. pylori cells grown in vitro; the best substrates were propionamide, acrylamide and acetamide. Polymerase chain reaction (PCR) amplification of an internal amiE sequence was obtained with each of 45 different H. pylori clinical isolates, suggesting that amidase is common to all H. pylori strains. A H. pylori mutant (N6-836) carrying an interrupted amiE gene was constructed by allelic exchange. No amidase activity could be detected in N6-836. In a N6-urease negative mutant, amidase activity was two- to threefold higher than in the parental strain N6. Crude extracts of strain N6 slowly hydrolysed formamide. This activity was affected in neither the amidase negative strain (N6-836) nor a double mutant strain deficient in both amidase and urease activities, suggesting the presence of an independent discrete formamidase in H. pylori. The existence of an aliphatic amidase, a correlation between the urease and amidase activities and the possible presence of a formamidase indicates that H. pylori has a large range of possibilities for intracellular ammonia production.
Mol Microbiol 1997 Sep
PMID:Identification and characterization of an aliphatic amidase in Helicobacter pylori. 936 23

We have localized, cloned and characterized the genes coding for the lytic system of the pneumococcal phage Dp-1. The lytic enzyme of this phage (Pal), previously identified as an N-acetyl-muramoyl-L-alanine amidase, shows a modular organization similar to that described for the lytic enzymes of Streptococcus pneumoniae and its bacteriophages. The construction of chimeric enzymes between pneumococcus and bacteria (or phages) that belong to different Gram-positive families has shown that the interchange of functional domains switches enzyme specificity. Interestingly, Pal appears to be a natural chimeric enzyme of intergeneric origin, that is the N-terminal domain was highly similar to that of the murein hydrolase coded by a gene found in the phage BK5-T that infects Lactococcus lactis, whereas the C-terminal domain was homologous to those found in the lytic enzymes of the pneumococcal system that is responsible for the binding to the choline residues present in the cell wall substrate. Biochemical analysis of Pal revealed that this enzyme shares important properties with those of the major LytA101 autolysin found in an atypical, clinical pneumococcal isolate. These peculiar characteristics have been ascribed to a modified C-terminal domain. The natural chimeric enzyme described here provides further support for the theory of modular evolution of proteins and its characteristics also furnish interesting clues on the molecular mechanisms involved in the more invasive types of atypical pneumococci.
Mol Microbiol 1997 Aug
PMID:The lytic enzyme of the pneumococcal phage Dp-1: a chimeric lysin of intergeneric origin. 937 1

Canavan disease (CD), a rare recessive autosomal genetic disorder, is characterized by early onset and a progressive spongy degeneration of the brain involving loss of the axon's myelin sheath. After a relatively normal birth, homozygous individuals generally develop clinical symptoms within months, and usually die within several years of the onset of the disease. A biochemical defect associated with this disease results in reduced activity of the enzyme N-acetyl-L-aspartate amidohydrolase (aspartoacylase) and affected individuals have less ability to hydrolyze N-acetyl-L-asparate (NAA) in brain and other tissues. As a result of aspartoacylase deficiency, NAA builds up in extracellular fluids (ECF) and is excreted in urine. From an analysis of the NAA biochemical cycle in various tissues of many vertebrate species, evidence is presented that there may be two distinct NAA circulation patterns related to aspartoacylase activity. These include near-field circulations in the brain and the eye, and a far-field systemic circulation involving the liver and kidney, the purpose of which in each case is apparently to regenerate aspartate (Asp) in order for it to be recycled into NAA as part of the still unknown function of the NAA cycle. Based on the authors' analysis, they have also identified several metabolic outcomes of the genetic biochemical aspartoacylase lesion. First, there is a daily induced Asp deficit in the central nervous system (CNS) that is at least six times the static level of available free Asp. Second, there is up to a 50-fold drop in the intercompartmental NAA gradient, and third, the ability of the brain to perform its normal intercompartmental cycling of NAA to Asp is terminated, and as a result, the only remaining long-term source of Asp for NAA synthesis is via nutritional supplementation of Asp or its metabolic precursors. Finally, the authors identify a potential maternal-fetal interaction that may be responsible for observed normal fetal development in utero, and that provides a rationale for, and suggests how, CD might respond to far-field nutritional, transplantation, or genetic engineering techniques to alter the course of the disease.
J Mol Neurosci 1997 Oct
PMID:Canavan disease. Analysis of the nature of the metabolic lesions responsible for development of the observed clinical symptoms. 940 92

Previous investigation [Tsui et al. (1996) Biochim. Biophys. Acta 1269: 41-46] showed that two active forms of alcohol dehydrogenase can be purified from grass carp. The use of a protease inhibitor and the results of SDS-PAGE analysis of the enzymes suggest that one form (ADH-C) is a proteolytic product of the other (ADH-I). In this study, the protease responsible for the cleavage was purified. The cleavage enzyme had a subunit molecular weight of 28 kDa. An inhibitor study identified it as a serine protease. It exhibited a strong chymotrypsin activity in both esterase and amidase assays with a pH optimum in the range 7.5-8.5. The purified chymotrypsin also cleaved the intact grass carp ADH-I into the two-fragment ADH-C, with an accompanying increase in enzyme activity. A similar effect was not found using horse liver alcohol dehydrogenase.
Biochem Mol Biol Int 1997 Dec
PMID:Identification of an "alcohol dehydrogenase-activating" protease in grass carp hepatopancreas as a chymotrypsin. 944 19


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