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Alessandro Pintar Meike Hensmann Kornelia Jumel Maureen Pitkeathly Stephen E. Harding Iain D. Campbell 《European biophysics journal : EBJ》1996,24(6):371-380
The SH2 domain from Fyn tyrosine kinase, corresponding to residues 155–270 of the human enzyme, was expressed as a GST-fusion protein in a pGEX-E. coli system. After thrombin cleavage and removal of GST, the protein was studied by heteronuclear NMR. Two different phosphotyrosyl-peptides were synthesized and added to the SH2 domain. One peptide corresponded to the regulatory C-terminal tail region of Fyn. Sequence-specific assignment of NMR spectra was achieved using a combination of1H-15N-correlated 2D HSQC,15N-edited 3D TOCSY-HMQC, and15N-edited 3D NOESY-HMQC spectra. By analysis of the -proton chemical shifts and NOE intensities, the positions of secondary structural elements were determined and found to correspond closely to that seen in the crystal structure of the, homologous, Src-SH2 domain.To investigate the internal dynamics of the protein backbone, T1 and T2 relaxation parameters were measured on the free protein, as well as on both peptide complexes. Analytical ultracentrifugation and dynamic light scattering were employed to measure the effect of concentration and peptide-binding on self-association. The results suggest that, at NMR-sample concentrations, the free protein is present in at least dimeric form. Phosphopeptide binding and lower concentration significantly, but not completely, shift the equilibrium towards monomers. The possible role of this protein association in the regulation of the Src-family tyrosine kinases is discussed.Abbreviations SH
Src homology
- GST
glutathione-S-transferase
- IPTG
isopropyl--D-galactopyranoside
- DTT
dithiothreitol
- PMSF
phenyl-methyl-sulphonyl-fluoride
- TBS
50 mM Tris, 150 mM NaCl, 5 mM DTT, pH 8.0
- MWCO
molecular weight cut off
- NMR
nuclear magnetic resonance
- HSQC
heteronuclear single-quantum correlation
- NOESY
nuclear Overhauser effect spectroscopy 相似文献
3.
The solution molecular weight and shape of the bacterial exopolysaccharides amylovoran and stewartan
Kornelia Jumel Klaus Geider Stephen E. Harding 《International journal of biological macromolecules》1997,20(4):251-258
Amylovoran, the acidic exopolysaccharide (EPS) of Erwinia amylovora, and stewartan, the capsular EPS of E. stewartii, were characterized by analytical ultracentrifugation and by size exclusion chromatography connected to dual detection of light scattering and mass. The average molecular weights of amylovoran and stewartan were determined as 1.0×106 and 1.7×106 Da, with polydispersity values (Mw/Mn) of 1.5 and 1.4, respectively. Based on the sugar composition and their molecular weight, both exopolysaccharides consist of approximately 1000 repeating units per molecule, this suggests a similar mechanism for chain length determination during biosynthesis of EPS in both organisms. 相似文献
4.
Application of denaturing gradient gel electrophoresis (DGGE) and temperature gradient gel electrophoresis (TGGE) in microbial ecology 总被引:107,自引:0,他引:107
Here, the state of the art of the application of denaturing gradient gel electrophoresis (DGGE) and temperature gradient gel electrophoresis (TGGE) in microbial ecology will be presented. Furthermore, the potentials and limitations of these techniques will be discussed, and it will be indicated why their use in ecological studies has become so important. 相似文献
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6.
Agata Karowicz-Bilinska Kornelia Kędziora-Kornatowska Grzegorz Bartosz 《Free radical research》2013,47(8):870-873
Intrauterine fetal growth restriction (IUGR), the main cause of premature delivery and fetal mortality, has been suggested to involve oxidative stress. We found elevated values of indices of oxidative stress in the blood serum of pregnant women with IUGR: increased levels of malondialdehyde and 4-hydroxyalkenals, decreased activity of α-1-antitrypsin and decreased total antioxidant capacity of the serum, with respect to healthy pregnancy. Twenty day treatment with 3 g of l-arginine and 75 mg of acetylsalicylic acid daily resulted in a decrease of the level of lipid peroxidation products and augmentation of α-1-antitrypsin activity. This study confirms the occurrence of oxidative stress in IUGR and demonstrates the beneficial effect of arginine/acetylsalicylic acid therapy in reducing oxidative stress in IUGR. 相似文献
7.
Further development of our recently published Glu(pNA)-containing peptides (Anal. Biochem. 428 (2012) 73–80) provided new fluorogenic substrates for the activated blood coagulation factor XIII. A first series was designed by incorporation of Glu(AMC) at the penultimate position from the N terminus. For the best derivative H-Tyr-Glu(AMC)-Val-Lys-Val-Ile-NH2, a moderate kcat/Km value of 34 s−1 M−1 was determined, which is more than 100-fold reduced compared with the previously reported Glu(pNA) substrates. Furthermore, two fluorescence resonance energy transfer (FRET) substrates were prepared by incorporation of an N-methyl-anthraniloyl fluorophore and a 2,4-dinitrophenyl quencher. Both substrates were excellently cleaved by FXIII-A2∗, which is generated from its zymogen by activation of thrombin in the presence of calcium ions. In the absence and presence of H-Gly-ethyl ester, kcat/Km values of 8010 and 8660 s−1 M−1, respectively, were found for the conversion of H-Lys(N(Me)Abz)-Glu(NH-(CH2)4-NH-Dnp)-Val-Lys-Val-Ile-Gly-NH2 (substrate 8). These values are more than 200-fold improved compared with the Glu(AMC) substrates. Substrate 8 is suitable for the measurement of FXIII-A2∗ activities in plasma samples as well as for in vitro measurements. Furthermore, it was used for the determination of the inhibitory potency of a newly synthesized chloromethyl ketone derivative, Cbz-Phe-Glu(CMK)-Val-Lys-Val-Ile-Gly-NH2, which was found to be a potent irreversible inhibitor of FXIII-A2∗. 相似文献
8.
Kornelia Neveling Lilian?A. Martinez-Carrera Irmgard H?lker Angelien Heister Aad Verrips Seyyed?Mohsen Hosseini-Barkooie Christian Gilissen Sascha Vermeer Maartje Pennings Rowdy Meijer Margot te?Riele Catharina?J.M. Frijns Oksana Suchowersky Linda MacLaren Sabine Rudnik-Sch?neborn Richard?J. Sinke Klaus Zerres R.?Brian Lowry Henny?H. Lemmink Lutz Garbes Joris?A. Veltman Helenius?J. Schelhaas Hans Scheffer Brunhilde Wirth 《American journal of human genetics》2013,92(6):946-954
Spinal muscular atrophy (SMA) is a heterogeneous group of neuromuscular disorders caused by degeneration of lower motor neurons. Although functional loss of SMN1 is associated with autosomal-recessive childhood SMA, the genetic cause for most families affected by dominantly inherited SMA is unknown. Here, we identified pathogenic variants in bicaudal D homolog 2 (Drosophila) (BICD2) in three families afflicted with autosomal-dominant SMA. Affected individuals displayed congenital slowly progressive muscle weakness mainly of the lower limbs and congenital contractures. In a large Dutch family, linkage analysis identified a 9q22.3 locus in which exome sequencing uncovered c.320C>T (p.Ser107Leu) in BICD2. Sequencing of 23 additional families affected by dominant SMA led to the identification of pathogenic variants in one family from Canada (c.2108C>T [p.Thr703Met]) and one from the Netherlands (c.563A>C [p.Asn188Thr]). BICD2 is a golgin and motor-adaptor protein involved in Golgi dynamics and vesicular and mRNA transport. Transient transfection of HeLa cells with all three mutant BICD2 cDNAs caused massive Golgi fragmentation. This observation was even more prominent in primary fibroblasts from an individual harboring c.2108C>T (p.Thr703Met) (affecting the C-terminal coiled-coil domain) and slightly less evident in individuals with c.563A>C (p.Asn188Thr) (affecting the N-terminal coiled-coil domain). Furthermore, BICD2 levels were reduced in affected individuals and trapped within the fragmented Golgi. Previous studies have shown that Drosophila mutant BicD causes reduced larvae locomotion by impaired clathrin-mediated synaptic endocytosis in neuromuscular junctions. These data emphasize the relevance of BICD2 in synaptic-vesicle recycling and support the conclusion that BICD2 mutations cause congenital slowly progressive dominant SMA. 相似文献
9.
Beyer Hannes M. Mikula Kornelia M. Kudling Tatiana V. Iwaï Hideo 《Extremophiles : life under extreme conditions》2019,23(6):669-679
Extremophiles - Self-splicing inteins are mobile genetic elements invading host genes via nested homing endonuclease (HEN) domains. All HEN domains residing within inteins are inserted at a highly... 相似文献
10.
Soumitra Paul Chowdhury Doreen Babin Martin Sandmann Samuel Jacquiod Loreen Sommermann Søren Johannes Sørensen Andreas Fliessbach Paul Mäder Joerg Geistlinger Kornelia Smalla Michael Rothballer Rita Grosch 《Environmental microbiology》2019,21(7):2426-2439
Long-term agricultural fertilization strategies gradually change soil properties including the associated microbial communities. Cultivated crops recruit beneficial microbes from the surrounding soil environment via root exudates. In this study, we aimed to investigate the effects of long-term fertilization strategies across field sites on the rhizosphere prokaryotic (Bacteria and Archaea) community composition and plant performance. We conducted growth chamber experiments with lettuce (Lactuca sativa L.) cultivated in soils from two long-term field experiments, each of which compared organic versus mineral fertilization strategies. 16S rRNA gene amplicon sequencing revealed the assemblage of a rhizosphere core microbiota shared in all lettuce plants across soils, going beyond differences in community composition depending on field site and fertilization strategies. The enhanced expression of several plant genes with roles in oxidative and biotic stress signalling pathways in lettuce grown in soils with organic indicates an induced physiological status in plants. Lettuce plants grown in soils with different fertilization histories were visibly free of stress symptoms and achieved comparable biomass. This suggests a positive aboveground plant response to belowground plant–microbe interactions in the rhizosphere. Besides effects of fertilization strategy and field site, our results demonstrate the crucial role of the plant in driving rhizosphere microbiota assemblage. 相似文献