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At least 163 records · Page 9Linked to original sources
PubMed1989

Pharmacological characterization of a new structural variant of 4-amidinophenylalanine amide-type synthetic thrombin inhibitor.

The synthetic thrombin inhibitor N alpha-(2-naphthylsulfonylglycyl)-4-amidinophenylalanyl-proline (1) was synthesized in order to evaluate the importance of the carboxyl group in its amine portion for fundamental pharmacodynamic and pharmacokinetic properties of these benzamidine derivatives. The compound is better tolerated in mice and rats than are similar compounds lacking this carboxyl group. It has a significantly longer plasma half-life in rabbits compared to the corresponding compound bearing piperidine instead of proline in the amide moiety. The main excretory route of 1 is via the bile. Hepatic uptake and/or biliary excretion show, however, another time course than that seen for the piperidide. Lower toxicity and more suitable pharmacokinetics may compensate for the loss of thrombin inhibitory potency of this new synthetic thrombin inhibitor.

Animals↗
PubMed1983

Structural variants of human glucose 6-phosphate dehydrogenase (G6PD): role of intracellular decay in the expression of deficiency.

The biochemical mechanisms of enzyme deficiency were investigated for two low activity G6PD variants, i.e. G6PD Mediterranean and G6PD Cagliari (a new variant). This study required the complete removal of leukocytes and platelets from blood samples and the use of sensitized procedures for assays of activity. G6PD Cagliari has a highly accelerated decay within circulating RBC and a near normal catalytic efficiency. The deficiency typical of G6PD Mediterranean (approx. 0.1% of the normal levels) is mediated by moderately reduced specific activity, while no clear decay was seen in mature RBC: however, the minute levels of activity that are observed in reticulocytes suggest that a strongly enhanced breakdown takes place during maturation of erythroid cells.

Erythrocyte Aging↗
PubMed1993

[Pathomorphologic structural variants of fetal membranes in oligohydroamnios].

Morphological heterogeneity of oligohydroamnion in 25 cases is shown. Inflammatory processes of hematogenic origin prevailed in 36% of cases; in 40% there were atrophic processes or microcystic transformation of the decidual endometrial glands against the background of the endometrial deficiency; dysontogenetic forms with the preservation of a large number of atrophic villi in the cytotrophoblast were observed in 24% cases. These variants should be taken into consideration when a differential treatment is developed.

Atrophy↗
PubMedDate not supplied

Identification with monoclonal antibody 140.240 of a structural variant of melanotransferrin shed by human melanoma cell lines in vitro.

Shedding by cultured human melanoma cells of a well-characterised cell- surface glycoprotein antigen known as "melanotransferrin" was studied with two monoclonal antibodies, 140.240 and 96.5. By means of [35S]-cysteine metabolically-labelled melanoma cells and immunoprecipitation studies, identification was made, by 140.240 in the spent media of two of six melanoma cell lines, of a new molecule of 100-kDa, aside from the 88-kDa molecule. Only the 88-kDa shed molecule was detected in the remaining four melanoma cell lines with both antibodies. None of nine clonal sublines derived from the two melanoma cell lines were found to shed the 100-kDa or 88-kDa molecule exclusively. Both shed antigens were released spontaneously to the medium from the live melanoma cells rather than as a result of cell death and lysis, since there was no obvious cell death or debris in the spent medium nor in the monolayer cells detected at the time of spent medium collection. Digestion of the isolated 100-kDa and 88-kDa shed molecules with N-glycanase followed by SDS-polyacrylamide gel electrophoresis resulted in the appearance of a single band of the 77-kDa molecule, which is deduced to be the polypeptide precursor of the cell-associated 87-kDa antigen. It is concluded that some melanoma lines shed the variant 100-kDa molecule, in addition to the 88-kDa molecule, and that both shed molecules and their cellular counterpart 87-kDa differ in their degrees of glycosylation.

Amidohydrolases↗
PubMed1988

An HLA-A2 population variant with structural polymorphism in the alpha 3 region.

The HLA-A2 antigen expressed by donor OZB can be distinguished from the main HLA-A2.1 subtype by isoelectric focusing - it is one charge unit more acidic - and by some alloreactive T-cell clones but not by cytolytic T lymphocyte lines. The structure of variant OZB has been examined by comparative peptide mapping with A2.1 and radiochemical sequence analysis. The two molecules were found to differ in a single tryptic peptide from the alpha 3 region, spanning residues 220-243. The amino acid sequence of this peptide from variant OZB revealed that there was only one amino acid change of Glu instead of Ala at position 236, a hitherto invariant residue in class I HLA antigens. All previously characterized HLA or H-2 natural variants have structural changes restricted to the alpha 1 and/or alpha 2 domains. Thus, variant OZB is unique in that (1) it has one amino acid change in alpha 3 and (2) it has no changes in alpha 1 and alpha 2. The only detected substitution of this variant may be accounted for by a single base change at the DNA level, suggesting that it might have resulted from a point mutation in the A2.1 gene. The structural features of variant OZB open a novel way to examine the influence of polymorphism in alpha 3 on cytolytic T-cell recognition of naturally occurring class I antigens.

Amino Acid Sequence↗
PubMed2006

Mannose-binding lectin genotype and invasive pneumococcal infection.

Invasive pneumococcal disease is a serious infection that primarily affects young children and elderly or immunocompromised persons, but it also can affect healthy persons. Mannose-binding lectin (MBL) is a mediator of innate host immunity that activates the complement pathway and directly opsonizes pathogens. Variant structural codon and promoter MBL alleles have been associated with susceptibility to infections. Sixty-three Belgian patients with invasive pneumococcal disease and 162 healthy Belgian controls were genotyped for MBL alleles. We found a nonsignificant increased risk between the MBL structural codon variants (52, 54, and 57) and invasive pneumococcal disease. Combining our data with similar data from Kronberg et al. (J Infect Dis 2002;185:1517-20) indicated that MBL structural variants contributed to a small but significant increased risk of invasive pneumococcal disease. On the other hand, the -221 and -550 promoter allele distribution and the prevalence of the combined MBL structural and promoter -221 variant alleles were not significantly different between the patient group and the control group.

Adolescent↗
PubMed1996

Variant GPI structure in relation to membrane-associated functions of a murine folate receptor.

Two variant sublines of murine L1210 leukemia cells (L1210A and L1210JF) overexpress the cell surface folate receptor (FR). The membrane bound FR in L1210A cells exhibited significantly (up to 17-fold) greater relative affinities for (6S)-N5-methyltetrahydrofolate, (6S)-N5-formyltetrahydrofolate and methotrexate compared to the FR in L1210JF cells. Furthermore, receptor-mediated transport of [3H]-(6S)-N5-methyltetrahydrofolate was much more efficient in L1210A cells compared to L1210JF cells. When solubilized with Triton X-100, the ligand binding characteristics of FR from both sublines resembled those of the receptor associated with L1210 JF cell membranes. N-terminal amino acid sequence analysis as well as RT-PCR analysis of the entire coding region revealed a single species of FR in both cells, identical to murine FR-alpha. The FR in L1210JF cells was sensitive to phosphatidylinositol specific phospholipase C (PI-PLC) indicating the presence of a glycosyl-phosphatidylinositol (GPI) membrane anchor while the FR in L1210A cells was resistant to PI-PLC; however, the FR in L1210A cells was released from plasma membranes by nitrous acid, as expected for GPI and its PI-PLC resistant structural variants. Treatment of L1210A cell membranes with mild base rendered the protein PI-PLC sensitive as expected for GPI anchors acylated in the inositol ring and also decreased the affinities of the membrane associated FR for reduced folates. When the cDNA for murine FR-alpha was expressed in parental L1210 cells the protein was PI-PLC resistant but was sensitive to PI-PLC when the cDNA was expressed in human 293 fibroblasts. In L1210JF, L1210A, and parental L1210 cells, several cell surface proteins, including FR, incorporated [3H]ethanolamine, a component of the GPI membrane anchor; however, the labeled proteins were released by PI-PLC only in L1210JF cells. The above results preclude any peculiarity of the FR polypeptide in either L1210 subline as the basis for the observed differences in PI-PLC sensitivity and membrane-associated functions of FR. Partial deglycosylation of membrane associated FR from either cell with N-glycanase did not influence its ligand binding characteristics. The results of this study lead to the hypothesis that variant GPI structures may modulate the function of a protein by influencing its conformation/topography in the membrane. Such effects may be identified by their disappearance/reduction upon detergent solubilization or mild base treatment of the membrane.

Amino Acid Sequence↗
PubMed2001

Native-like tertiary structure formation in the alpha-domain of a hen lysozyme two-disulfide variant.

Structure formation in two species of the two-disulfide variant of hen lysozyme was investigated by means of CD spectroscopy, disulfide exchange measurement, and 1H-NMR spectroscopy. One species, 2SS [6-127, 30-115], which contained the two disulfide bonds found in the alpha-domain of authentic lysozyme, had amounts of secondary and tertiary structures, and bacteriolytic activity comparable to those of authentic lysozyme, and showed a cooperative thermal unfolding. By contrast, the other species, 2SS [64-80, 76-94], which contained the beta-domain disulfide bond as well as the inter-domain one, had a limited amount of secondary structure and little tertiary structure. Disulfide-exchange did not occur for 2SS [6-127, 30-115], whereas it occurred for 2SS [64-80, 76-94], indicating that the protein main-chain fold coupled with the formation of two disulfide bonds is relatively stable for the former variant, while unstable for the latter. 1H-NMR spectra of 2SS [6-127, 30-115] showed that native-like local environment is present within the region that corresponds to the alpha-domain, while it is absent within the region that corresponds to the beta or inter-domain. These results indicate that the alpha-domain of hen lysozyme can be an independent folding domain at equilibrium. Although the bipartite nature in the structure formation of hen lysozyme is similar to that reported for alpha-lactalbumin, differences exist between the disulfide-intermediates of the two proteins in terms of the structural domain that accomplishes tertiary structure.

Animals↗
PubMed2026

Cross-kingdom genomic variation in chicken gut microbiomes: insights from China's diverse local breeds.

BACKGROUND: The gut microbiome possesses substantial genetic diversity that supports microbial adaptation, but the genomic variation patterns across its prokaryotic and viral populations remain incompletely characterized. RESULTS: Through integrated metagenomic and metatranscriptomic analysis of ten indigenous chicken breeds from China, we recovered 1527 representative prokaryotic MAGs, 37,555 representative DNA viral contigs, and 1867 representative RNA viral contigs (primarily comprising Bacillota/Bacteroidota, Uroviricota, and Lenarviricota/Pisuviricota, respectively). By integrating complementary short-read and long-read metagenomics with metatranscriptomics, we identified structural variants (SVs) and single-nucleotide variants (SNVs) in these cross-kingdom genomes. Positive SV-SNV density correlations occurred consistently across all microbial groups, indicating coordinated mutational processes. DNA viruses exhibited the highest variant prevalence (86.9% SNVs, 47.7% SVs), with temperate phages accumulating significantly more variants than virulent phages. Functionally, prokaryotic variants accumulated in carbohydrate metabolism and amino acid metabolism, while viral variants demonstrated broad metabolic hijacking. Horizontal gene transfer (HGT) was characterized by a strong virus-associated signature (69.40% of 536 events) and marked by an asymmetric pattern, with phage-to-bacteria (P-to-B) flow alone constituting 37.50% of all events. Random forest analysis revealed a strong bidirectional predictive relationship between SV and SNV densities across prokaryotic, DNA viral, and RNA viral populations, suggesting coupled genomic instability. Niche breadth emerged as a major driver of SNVs across kingdoms and was positively correlated with variant density. In prokaryotes, HGT events significantly shaped variant patterns. For viruses, genomic GC content was an important factor and consistently showed a negative correlation with SNV density in both DNA and RNA viruses. CONCLUSIONS: These findings demonstrate that coordinated mutational processes and kingdom-specific intrinsic factors drive genomic variation, with viruses serving as key genetic exchange vectors in chicken gut ecosystems. Video Abstract.

Animals↗
PubMed1985

A structural somatic variant of the Kk antigen is generated by point mutation.

We have previously selected structural variants of the Kk antigen from a (C3 X D2)F1 T-cell lymphoma. Those mutants were identified by the loss of certain epitopes defined by monoclonal antibodies. The variant Kk molecule from HK13.S3 cells is no longer recognized by 40% of the trinitrophenyl-specific, Kk-restricted cytotoxic T lymphocytes. Here we report on the primary structure of the altered Kk molecules from the cell line HK13.S3. Comparison with the parental Kk reveals a single base pair exchange, GCG to GTG, that results in an alanine to valine exchange in position 40 of the protein. This observation emphasizes that minor structural alterations in class I molecules may have a strong effect on the H-2-restricted T-cell response.

Amino Acid Sequence↗