Abstract：
:Fungal infections are a growing problem in contemporary medicine, yet only a few antifungal agents are used in clinical practice. In our laboratory we proposed the enzyme L-glutamine: D-fructose-6-phosphate amidotransferase (EC 2.6.1.16) as a new target for antifungals. The structure of this enzyme consists of two domains, N-terminal and C-terminal ones, catalysing glutamine hydrolysis and sugar-phosphate isomerisation, respectively. In our laboratory a series of potent selective inhibitors of GlcN-6-P synthase have been designed and synthesised. One group of these compounds, including the most studied N3-(4-methoxyfumaroyl)-l-2,3-diaminopropanoic acid (FMDP), behave like glutamine analogs acting as active-site-directed inactivators, blocking the N-terminal, glutamine-binding domain of the enzyme. The second group of GlcN-6-P synthase inhibitors mimic the transition state of the reaction taking place in the C-terminal sugar isomerising domain. Surprisingly, in spite of the fact that glutamine is the source of nitrogen for a number of enzymes it turned out that the glutamine analogue FMDP and its derivatives are selective against GlcN-6-P synthase and they do not block other enzymes, even belonging to the same family of glutamine amidotransferases. Our molecular modelling studies of this phenomenon revealed that even within the family of related enzymes substantial differences may exist in the geometry of the active site. In the case of the glutamine amidotransferase family the glutamine binding site of GlcN-6-P synthase fits a different region of the glutamine conformational space than other amidotransferases. Detailed analysis of the interaction pattern for the best known, so far, inhibitor of the sugar isomerising domain, namely 2-amino-2-deoxy-D-glucitol-6-phosphate (ADGP), allowed us to suggest changes in the structure of the inhibitor that should improve the interaction pattern. The novel ligand was designed and synthesised. Biological experiments confirmed our predictions. The new compound named ADMP is a much better inhibitor of glucosamine-6-phosphate synthase than ADGP.
journal_name
Acta Biochim Poljournal_title
Acta biochimica Polonicaauthors
Wojciechowski M,Milewski S,Mazerski J,Borowski Esubject
Has Abstractpub_date
2005-01-01 00:00:00pages
647-53issue
3eissn
0001-527Xissn
1734-154Xpii
20051108journal_volume
52pub_type
杂志文章,评审abstract：:The aim of this study was to compare the content of carotenoids in seventeen cultivars of carrots grown in Poland. Conventional orange cultivars with rarely grown were compared: white, yellow and purple with yellow core cultivars. To determine the content of carotenoids, extracts from lyophilized carrot roots were pre...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：2012-01-01 00:00:00
abstract：:We examined the molecular basis of factor IX deficiency in 53 unrelated Polish patients with hemophilia B. Heteroduplex analysis and direct sequencing of polymerase chain reaction (PCR) products were applied to identify the gene defect. Forty-three different point mutations were detected in the factor IX gene of 47 pa...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：1999-01-01 00:00:00
abstract：:Exposure to environmental pollutants often leads to an upsurge in the production of reactive oxygen species (ROS). ROS oxidize cellular fatty acids to produce lipid peroxyl radicals, subsequently transformed into lipid peroxides, which decrease membrane fluidity and increase the activity of various enzymes implicated ...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：2013-01-01 00:00:00
abstract：:1. The amino acid composition of wheat germ EF2 differs to some extent from that of elongation factors from mammals and bacteria. 2. The purified wheat germ EF2, similarly as the factors from other sources, is active in the: EF1-dependent polymerization of phenylalanine; ribosome-dependent GTP hydrolysis; binding of g...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：1977-01-01 00:00:00
abstract：:Many nuclear genes encoding mitochondrial proteins require specific localization of their mRNAs to the vicinity of mitochondria for proper expression. Studies in Saccharomyces cerevisiae have shown that the cis-acting signal responsible for subcellular localization of mRNAs is localized in the 3' UTR of the transcript...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：2007-01-01 00:00:00
abstract：:We found that it is possible to use eriochrome black T as a dye for agarose gel electrophoresis of DNA. The presence of the dye does not change the migration rate of DNA and does not influence the electrophoretical picture. ...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：1991-01-01 00:00:00
abstract：:1. A lytic enzyme was isolated from Vi phage III-induced lysate of Salmonella typhi, and purified about 200-fold by chromatography on IRC-50, CM-cellulose, and Sephadex G-75 columns. 2. Both E. coli B murein and muropeptide C6 were digested on incubation with the lytic enzyme. The main product of murein and muropeptid...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：1975-01-01 00:00:00
abstract：:1. The interaction of copper(II) with inosine, 2'-deoxyinosine, 1-methylinosine, 7-deazainosine, 6-methoxypurine riboside and IMP was examined. 2. Copper binds with the purine base of the nucleosides, and in IMP also with the phosphate group. Non interaction with ribose hydroxyl groups was observed. 3. In non-aqueous ...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：1978-01-01 00:00:00
abstract：:The aim of this study was to analyse the correlation between HPV16 E6 variants and the physical status of viral genome (integrated, mixed, episomal) among patients with cervical cancer (n=40) and low-grade squamous intraepithelial lesions - LSIL (n=40). The study was performed on 80 HPV16 positive samples. HPV16 E6 va...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：10.18388/abp.2016_1364
更新日期：2017-01-01 00:00:00
abstract：:Natural and synthetic derivatives of benzo-γ-pyrones (i.e. flavones, chromones, and coumarins) and their synthetic analogues possess a wide range of biological properties in vitro and in vivo. In this paper we investigated the influence of two hydrazone compounds of chromones, 3-{[(2-dimethoxytiophosphoryl)-2-methylhy...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：2013-01-01 00:00:00
abstract：:In this paper transcriptional factor IIIA (TFIIIA) has been used as a probe for identity of three-dimensional-structure of eukaryotic 5S rRNAs. I was interested in finding a common motif in plant and Xenopus 5S rRNAs for TFIIIA recognition. I found that the two eukaryotic 5S rRNAs (from wheat germ and lupin seeds) are...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：1994-01-01 00:00:00
abstract：:Cyclosporine A (CsA), a widely used immunosuppressive drug, exerts nephrotoxic activities, as demonstrated by increased tubulointerstitial fibrosis, inflammation and podocyte damage. Recently, a number of microRNAs expressed in the kidney have been reported to be elevated during renal damage. Our aim was to investigat...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：10.18388/abp.2018_2658
更新日期：2018-11-27 00:00:00
abstract：:Intercalative binding of the antitumor drugs ametantrone and mitoxantrone to the dodecamer duplex d(CGCGAGCTCGCG)2 was studied by applying molecular dynamics in water with the GROMOS 87 force field. A number of reasonable binding orientations were tested by short pre-simulations. It was shown that in energetically fav...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：1998-01-01 00:00:00
abstract：:Stem cells (SC) research is an important part of biotechnology that could lead to the development of new therapeutic strategies. A lot of effort has been put to understand biology of the stem cells and to find genes and subsequently proteins that are responsible for their proliferation, self-renewal and differentiatio...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章,评审
doi：
更新日期：2005-01-01 00:00:00
abstract：:Nematodes were found to synthesize phosphorylcholine-containing molecules not present in higher organisms, i.e. phosphorylcholine-substituted glycosphingolipids and (glyco)proteins. Investigations on the biosynthesis of these structures provided first biochemical evidence for the presence of the Kennedy and Bremer-Gre...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：0350041239
更新日期：2003-01-01 00:00:00
abstract：:The endogenous electric field may provide an important signal for directional cell migration during cancer metastasis but the mechanism of cell electrotaxis is poorly understood. It was postulated that microtubules play a central role in the polarization and directional migration of several types of cells. In this pap...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：10.18388/abp.2015_1019
更新日期：2015-01-01 00:00:00
abstract：:Several studies employed the genome-wide association (GWA) analysis of single-nucleotide polymorphisms (SNPs) to identify susceptibility regions in colorectal cancer (CRC). However, the functional studies exploring the role of associating SNPs with cancer biology are limited. Herein, using chromatin immunoprecipitatio...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：10.18388/abp.2019_2775
更新日期：2019-09-17 00:00:00
abstract：:Two structurally related compounds, phenyl dithiocarbamate sodium salt (I) and p-phenylene-bis (dithiocarbamate) sodium salt (II) were prepared by reaction of the parent aniline and p-phenylenediamine with CS₂ in the presence of sodium hydroxide. These water soluble compounds were characterized by spectroscopic techni...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：2010-01-01 00:00:00
abstract：:Two different molecular forms of bacteriolytic endo-N-acetylmuramidase (EC 3.2.1.17) were found in the Acanthamoeba castellanii culture. The enzymes were separated by column chromatography on DEAE-Sephadex or by polyacrylamide-gel electrophoresis. In young cultures only one molecular form of the enzyme was selectively...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：1978-01-01 00:00:00
abstract：:This article reviews the evidence for the danger model in the context of immune response to tumors and the insufficiency of the immune system to eliminate tumor growth. Despite their potential immunogenicity tumors do not induce significant immune responses which could destroy malignant cells. According to the danger ...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章,评审
doi：
更新日期：2002-01-01 00:00:00
abstract：:Cytokines trigger coagulant and fibrinolytic systems in sepsis to result in Disseminated Intravascular Coagulation (DIC) that is an important complication and leads to disseminated hemorrhages and multi-organ failure. High Mobility Group B1 DNA Binding (HMGB1) protein is a cytokine taking part in systemic inflammatory...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：2012-01-01 00:00:00
abstract：:An approximately threefold increase in glycogenolytic activity of the neutral alpha-1,4-glucosidase and a twofold increase in the same activity of the acid isoform have been found in extracts of anaplastic astrocytoma and glioblastoma multiforme tumors of brain tissue. "Maltase activity" of the respective enzymes incr...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：2001-01-01 00:00:00
abstract：:In plant cells, phospholipids are not only membrane components but also act as second messengers interacting with various proteins and regulating diverse cellular processes, including stress signal transduction. Here, we report studies on the effects of various phospholipids on the activity and expression of maize wou...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：2011-01-01 00:00:00
abstract：:Efficient synthesis of two small eukaryotic polypeptides of human and plant origin was carried out using a novel expression/secretion yeast vector, pYET. The yield was optimized in respect of the yeast strain, expression cassette construction, promoter regulation and culture conditions. Both cloned genes code for biot...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：1996-01-01 00:00:00
abstract：:The urinary tract is vulnerable to frequent challenges from environmental microflora. Uropathogenic Escherichia coli (UPEC) makes a major contribution to urinary tract infection (UTI). Previous studies have characterized positive roles of non-histone nuclear protein HMGN2 in lung epithelial innate immune response. In ...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：10.18388/abp.2017_1622
更新日期：2018-01-01 00:00:00
abstract：:The PCR conditions have been optimized to make the process faster and more economical. When short DNA fragments are to be amplified, the time of denaturation, annealing and extension steps can be as short as 1 s each, and the yield of PCR product is still high, sufficient for many types of analysis. The PCR can be don...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:Ammonium salt of N-(dithiocarboxy)sarcosine (DTCS) chelated to ferrous salt was tested as an NO-metric spin trap at room temperature for ex vivo measurement of (.)NO production in murine endotoxaemia. In a chemically defined in vitro model system EPR triplet signals of NO-Fe(DTCS)(2) were observed for as long as 3 hou...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：035003799
更新日期：2003-01-01 00:00:00
abstract：:1. The lupin cotyledons contain two cytoplasm-specific lysine tRNAs, one chloroplast-specific, one mitochondria-specific species, and three species common to all the cell compartments investigated; the lysine tRNAs were separated by reversed-phase chromatography (RPC-5). 2. The two cytoplasmic lysine tRNAs are predomi...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：1978-01-01 00:00:00
abstract：:In the haemolymph of Oniscidea haemocyanin exists mainly in the form of hexamer 16S (90%); the 5S and 24S components are present in small amounts. Alkaline dissociation of the examined 16S haemocyanins is dependent on pH and divalent cations (Ca2+,Mg2+). The 16S component consists of 23-24.5% acidic amino acids, 15-18...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：1991-01-01 00:00:00
abstract：:Glutathione-S-transferase (GST) a Phase-II drug detoxification enzyme, was detected in Setaria cervi, a bovine filarial parasite. In vitro effect of diethylcarbamazine, butylated hydroxyanisole and phenobarbitone on the GST of adult female S. cervi was assayed by the addition of these compounds in the maintenance medi...
journal_title：Acta biochimica Polonica
pub_type： 杂志文章
doi：
更新日期：2005-01-01 00:00:00
