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1.
The serum enzyme pseudocholinesterase from 14 individuals of the rare phenotype S (silent gene) has been investigated by means of various biochemical and immunological techniques. By use of more sensitive methods than standard assays, it is demonstrated that the enzyme deficiency is not complete in all cases and that certain of the sera which contain trace amounts of enzyme activity differ with respect to their immunological reactions and their electrophoretic esterase pattern. 相似文献
2.
John P. Baker 《Biochemical genetics》1978,16(11-12):1181-1186
3.
P K Das 《Human heredity》1973,23(1):88-96
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Identification of the mutation responsible for a case of plasmatic apolipoprotein CII deficiency (Apo CII-Bari) 总被引:1,自引:0,他引:1
C Crecchio A Capurso G Pepe 《Biochemical and biophysical research communications》1990,168(3):1118-1127
We studied a case of familial Apolipoprotein CII deficiency. By Southern hybridization, amplification and sequence analysis, the genetic defect was identified. It consists in a point mutation C- greater than G in the third exon of the gene causing a premature stop codon. Truncated at the aa. 36 of the mature form, the protein loses its functional domains, becomes inefficient and cannot be detected in the plasma, because of its high instability. The mutation destroys an RsaI site, present in the normal gene sequence. This point mutation is useful in the diagnosis of this Apolipoprotein CII deficiency. 相似文献
6.
We propose that a beta-turn-beta structure, which plays a critical role in exonucleolytic proofreading in the bacteriophage T4 DNA polymerase, is also present in the Saccharomyces cerevisiae DNA pol delta. Site-directed mutagenesis was used to test this proposal by introducing a mutation into the yeast POL3 gene in the region that encodes the putative beta-turn-beta structure. The mutant DNA pol delta has a serine substitution in place of glycine at position 447. DNA replication fidelity of the G447S-DNA pol delta was determined in vivo by using reversion and forward assays. An antimutator phenotype for frameshift mutations in short homopolymeric tracts was observed for the G447S-DNA pol delta in the absence of postreplication mismatch repair, which was produced by inactivation of the MSH2 gene. Because the G447S substitution reduced frameshift but not base substitution mutagenesis, some aspect of DNA polymerase proofreading appears to contribute to production of frameshifts. Possible roles of DNA polymerase proofreading in frameshift mutagenesis are discussed. 相似文献
7.
Identification and characterization of mutations responsible for a runaway replication phenotype of plasmid R1 总被引:5,自引:0,他引:5
Initiation of replication of the resistance plasmid R1 is carefully regulated by the two negatively acting factors, CopA and CopB. It is shown here that the temperature-dependent runaway-replication phenotype of an R1 plasmid mutant is caused by two point mutations in each of the promoters for the genes of these control factors. Expression of the two genes is affected in the following way: (1) one C-to-T transition in the putative -35 box of the copB-repA operon creates a two- to three-fold stronger promoter from which expression is temperature-dependent; (2) another C-to-T transition in a G + C-rich area immediately downstream from the -10 box of the copA promoter reduces expression of the copA gene three-fold. The phenotypic consequences of the two mutations are discussed in the light of the current model for R1 replication control. 相似文献
8.
The autosomal recessive mutation short antennae (sa) causes considerable shortening of antennae in male and female Mediterranean flour moths (Ephestia kuehniella Zeller). However, the sa phenotype can be suppressed by several physical factors, making sa moths indistinguishable from wild-type moths (sa(WT)). This can be done by subjecting larva and pupa to a higher temperature (25 degrees C), to lithium ions, or to an alternate electric field. The first half of pupal development was found to be the sensitive period for the sa(WT) phenotype. The sa(WT) phenotype is stable and cannot be reverted to the original sa type by physical or chemical factors. The sa(WT) phenotype is transmitted to future generations. When crossed with typical sa moths, the sa(WT) phenotype is inherited either as a dominant character if carried by males or a semidominant character if carried by females. We compared proteins of the ejaculate, accessory gland secretions, and spermatophore in sa, sa(WT), and wild-type males and found considerable differences between sperm proteins of sa(WT), sa, and wild-type males. The sa(WT) phenotype influences the mating success of males: sa(WT) males mated successfully with any females, whereas typical sa males were less successful in mating and then mainly with females of the same phenotype. 相似文献
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10.
Nishiyama T Kobori T Arai K Ogura K Ohnuma T Ishii K Hayashi K Hiratsuka A 《Archives of biochemistry and biophysics》2006,454(1):72-79
Glucuronidation is a major metabolic pathway in the biotransformation of many xenobiotics and endogeneous compounds. There have been many studies on the formation of O-, N- or S-glucuronides and identification of the UDP-glucuronosyltransferase (UGT) isoforms responsible for the formation of these glucuronides. However, there is no information available on which UGT isoform(s) catalyzes C-glucuronidation. In the present study, 16 human UGTs (UGTs 1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B10, 2B11, 2B15, 2B17 and 2B28) were cloned and expressed in baculovirus-infected insect cells and investigated to determine their C-glucuronidating activity toward phenylbutazone (PB). Among the UGT isoforms investigated, only UGT1A9 catalyzed PB C-glucuronidation. Human liver and kidney microsomes, which are well known to express UGT1A9, had C-glucuronidating activity toward PB. However, the jejunum, which did not express UGT1A9, had no C-glucuronidating activity. These results demonstrate for the first time that PB C-glucuronidation is catalyzed by only UGT1A9. 相似文献
11.
Egashira M Takase H Yamamoto I Tanaka M Saito H 《Archives of biochemistry and biophysics》2011,511(1-2):101-106
Human serum amyloid A (SAA) is a precursor protein of amyloid fibrils. Although several studies have been performed, a detailed understanding of the molecular mechanism for SAA fibrillation remains elusive. Glycosaminoglycans such as heparin are suggested to serve as scaffolds in amyloid fibril formation in some cases. In the present study, amyloidogenic properties of synthetic fragment peptides corresponding to the N-terminal (residues 1-27), central (residues 43-63), and C-terminal (residues 77-104) regions of SAA molecule induced by heparin were examined using fluorescence, circular dichroism (CD), and electron microscopy. Fluorescence and CD measurements demonstrated that SAA (1-27) peptide is evidently involved in heparin-induced amyloidogenesis. Correspondingly, relatively minor changes in fluorescence and a quite different pattern in the CD spectrum were observed in SAA (43-63) peptide. In contrast, SAA (77-104) peptide did not show any changes induced by heparin. Transmission electron microscopy indicated that SAA (1-27) peptide forms short and straight fibrils, whereas SAA (43-63) peptide forms much longer and seemingly elastic fibrils. These results suggest that the N-terminal region plays a crucial role as a rigid core and the central region facilitates the elongation of fibrils in heparin-induced amyloidogenesis of SAA molecule. 相似文献
12.
T. A. Muranova I. G. Shvyrkova A. I. Rykunova 《Russian Journal of Bioorganic Chemistry》2000,26(3):164-168
The antiadhesive effect of dog blood serum described previously was shown to be associated with the proteolytic activity of
the serum components. A protease exhibiting this antiadhesive effect was isolated by several fractionation stages and identified
with plasmin. 相似文献
13.
The antiadhesive effect of dog blood serum described previously was shown to be associated with the proteolytic activity of the serum components. The protease exhibiting this antiadhesive effect was isolated by several fractionation stages and identified with plasmin. 相似文献
14.
Rocket immuno-electrophoresis and enzyme-linked immunosorbent assays were used to estimate the amount of cholinesterase present in 29 apparent silent homozygotes. 26 of these samples were segregated into four groups representing zero, very low, low and high levels of immunoreactive protein. These groups may represent the genotypes E1sE1s, E1sE1t, E1tE1t and a new genotype E1xE1x, respectively. The possible genotypes of the remaining 3 individuals are discussed. 相似文献
15.
Identification of mutations in cystatin B, the gene responsible for the Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1). 总被引:4,自引:0,他引:4
M D Lalioti M Mirotsou C Buresi M C Peitsch C Rossier R Ouazzani M Baldy-Moulinier A Bottani A Malafosse S E Antonarakis 《American journal of human genetics》1997,60(2):342-351
Progressive myoclonus epilepsy (EPM1) is an autosomal recessive disorder, characterized by severe, stimulus-sensitive myoclonus and tonic-clonic seizures. The EPM1 locus was mapped to within 0.3 cM from PFKL in chromosome 21q22.3. The gene for the proteinase inhibitor cystatin B was recently localized in the EPM1 critical region, and mutations were identified in two EPM1 families. We have identified six nucleotide changes in the cystatin B gene of non-Finnish EPM1 families from northern Africa and Europe. The 426G-->C change in exon 1 results in a Gly4Arg substitution and is the first missense mutation described that is associated with EPM1. Molecular modeling predicts that this substitution severely affects the contact of cystatin B with papain. Mutations in the invariant AG dinucleotides of the acceptor sites of introns 1 and 2 probably result in abnormal splicing. A deletion of two nucleotides in exon 3 produces a frameshift and truncates the protein. Therefore, these four mutations are all predicted to impair the production of functional protein. These mutations were found in 7 of the 29 unrelated EPM1 patients analyzed, in homozygosity in 1, and in heterozygosity in the others. The remaining two sequence changes, 431G-->T and 2575A-->G, probably represent polymorphic variants. In addition, a tandem repeat in the 5' UTR (CCCCGCCCCGCG) is present two or three times in normal alleles. It is peculiar that in the majority of patients no mutations exist within the exons and splice sites of the cystatin B gene. 相似文献
16.
Mömke S Kerkmann A Wöhlke A Ostmeier M Hewicker-Trautwein M Ganter M Kijas J;International Sheep Consortium Distl O 《PloS one》2011,6(5):e18943
Junctional epidermolysis bullosa (JEB) is a hereditary mechanobullous skin disease in humans and animals. A Herlitz type JEB was identified in German Black Headed Mutton (BHM) sheep and affected lambs were reproduced in a breeding trial. Affected lambs showed skin and mucous membranes blistering and all affected lambs died within the first weeks of life. The pedigree data were consistent with a monogenic autosomal recessive inheritance. Immunofluorescence showed a reduced expression of laminin 5 protein which consists of 3 subunits encoded by the genes LAMA3, LAMB3 and LAMC2. We screened these genes for polymorphisms. Linkage and genome-wide association analyses identified LAMC2 as the most likely candidate for HJEB. A two base pair deletion within exon 18 of the LAMC2 gene (FM872310:c.2746delCA) causes a frameshift mutation resulting in a premature stop codon (p.A928*) 13 triplets downstream of this mutation and in addition, introduces an alternative splicing of exon 18 LAMC2. This deletion showed a perfect co-segregation with HJEB in all 740 analysed BHM sheep. Identification of the LAMC2 deletion means an animal model for HJEB is now available to develop therapeutic approaches of relevance to the human form of this disease. 相似文献
17.
Wang Q Perepelov AV Wen L Shashkov AS Wang X Guo X Knirel YA Wang L 《Glycobiology》2012,22(2):281-287
The O-antigen is one of the most variable Gram-negative cell constituents, and its specificity is important for bacterial niche adaptation. The observed diversity of O-antigen forms is mainly due to genetic variations in O-antigen gene clusters. Less common is a change of gene function due to nucleotide substitution; a new instance of which is reported here. The O-antigens of E. coli O107 and O117 have similar structures differing only in a single sugar residue (GlcNAc in O107 substituted for Glc in O117). These O-antigen gene clusters contain the same set of 11 genes and share 98.6% overall DNA identity. The function of the genes in the gene clusters have been proposed previously, and a glycosyltransferase gene (wclY) with nucleotide polymorphism in each strain was proposed to transfer different sugars in different strains. To identify the gene responsible for the transfer of different sugars, wclY mutants of E. coli O107 and O117 were constructed, and each mutant was complemented with the wclY genes cloned from both O107 and O117. Structural analysis of the O-antigens of the four recombinant strains identified wclY as a Glc-transferase in O117 and a GlcNAc-transferase in O107. The evolutionary relationship of E. coli O107 and O117 O-antigens is also discussed. 相似文献
18.
Molecular targets of a human HNF1 alpha mutation responsible for pancreatic beta-cell dysfunction 总被引:7,自引:0,他引:7
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The reverse tetracycline-dependent transactivator system was employed in insulinoma INS-1 cells to achieve controlled inducible expression of hepatocyte nuclear factor-1 alpha (HNF1 alpha)-P291fsinsC, the most common mutation associated with subtype 3 of maturity-onset diabetes of the young (MODY3). Nuclear localized HNF1 alpha-P291fsinsC protein exerts its dominant-negative effects by competing with endogenous HNF1 alpha for the cognate DNA-binding site. HNF1 alpha controls multiple genes implicated in pancreatic beta-cell function and notably in metabolism- secretion coupling. In addition to reduced expression of the genes encoding insulin, glucose transporter-2, L-pyruvate kinase, aldolase B and 3-hydroxy-3-methylglutaryl coenzyme A reductase, induction of HNF1 alpha-P291fsinsC also significantly inhibits expression of mitochondrial 2-oxoglutarate dehydrogenase (OGDH) E1 subunit mRNA and protein. OGDH enzyme activity and [(14)C]pyruvate oxidation were also reduced. In contrast, the mRNA and protein levels of mitochondrial uncoupling protein-2 were dramatically increased by HNF1 alpha-P291fsinsC induction. As predicted from this altered gene expression profile, HNF1 alpha-P291fsinsC also inhibits insulin secretory responses to glucose and leucine, correlated with impaired nutrient-evoked mitochondrial ATP production and mitochondrial membrane hyperpolarization. These unprecedented results suggest the molecular mechanism of HNF1 alpha-P291fsinsC causing beta-cell dysfunction. 相似文献
19.
Human serum cholinesterase (BChE) has a putative sulfhydryl group (Cys-66) which is unreactive toward conventional alkylating agents such as iodoacetic acid, raising the possibility that this group is blocked in native BChE. In order to test this further, we examined the reactivity of BChE towards the sulfhydryl-specific reagent S- mercuric-N-dansylcysteine (SMNDC). Stoichiometric binding of 4 mol SMNDC/mol of tetrameric enzyme was observed in fluorescence titration experiments, with retention of catalytic activity. SMNDC remained bound to the protein during SDS-polyacrylamide gel electrophoresis in the absence of reducing agent and the fluorescence pattern observed under U.V. light coincided with the Coomassie Blue stained bands. Addition of excess dithiothreitol to the SMNDC-labeled enzyme resulted in the complete removal of bound SMNDC. Thus, Cys-66 appears to be present in the free sulfhydryl form in BChE, analogous to the corresponding free thiol group (Cys-231) of Torpedo californica acetylcholinesterase. As is the case with the latter species, BChE (labeled or unlabeled) is inactivated by 1.0 x 10(-4)M ZnSO4. 相似文献
20.
E M Scott 《Biochemical and biophysical research communications》1970,38(5):902-906