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161.
Multidimensional heteronuclear NMR studies have been applied to the
resonance assignment and conformational analysis of 13C-enriched
Neu5Acalpha2-3Galbeta1-4Glc. It is demonstrated that three-dimensional
ROESY-HSQC experiments provide through-space distance restraints which
cannot be observed with conventional homonuclear 1H techniques due to
resonance overlap. In particular, connectivities demonstrating the
existence of the "anti" conformation about the Galbeta1-4Glc glycosidic
linkage are unambiguously observed. It is shown that 13C isotopic
enrichment of the trisaccharide at a level >95% enables straightforward
measurement of trans-glycosidic 1H-13C and 13C-13C coupling constants and a
Karplus-type relation is derived for the latter. In total 15 conformational
restraints were obtained for the trisaccharide in aqueous solution, all of
which were in excellent agreement with theoretical parameters computed from
a 5 ns molecular dynamics simulation of the glycan.
相似文献
162.
Tetramer-dimer equilibrium of oxyhemoglobin mutants determined from auto-oxidation rates. 总被引:1,自引:0,他引:1 下载免费PDF全文
N. Griffon V. Baudin W. Dieryck A. Dumoulin J. Pagnier C. Poyart M. C. Marden 《Protein science : a publication of the Protein Society》1998,7(3):673-680
One of the main difficulties with blood substitutes based on hemoglobin (Hb) solutions is the auto-oxidation of the hemes, a problem aggravated by the dimerization of Hb tetramers. We have employed a method to study the oxyHb tetramer-dimer equilibrium based on the rate of auto-oxidation as a function of protein concentration. The 16-fold difference in dimer and tetramer auto-oxidation rates (in 20 mM phosphate buffer at pH 7.0, 37 degrees C) was exploited to determine the fraction dimer. The results show a transition of the auto-oxidation rate from low to high protein concentrations, allowing the determination of the tetramer-dimer dissociation coefficient K4,2 = [Dimer] 2/[Tetramer]. A 14-fold increase in K4,2 was observed for addition of 10 mM of the allosteric effector inositol hexaphosphate (IHP). Recombinant hemoglobins (rHb) were genetically engineered to obtain Hb with a lower oxygen affinity than native Hb (Hb A). The rHb alpha2beta2 [(C7) F41Y/(G4) N102Y] shows a fivefold increase in K4,2 at pH 7.0, 37 degrees C. An atmosphere of pure oxygen is necessary in this case to insure fully oxygenated Hb. When this condition is satisfied, this method provides an efficient technique to characterize both the tetramer-dimer equilibrium and the auto-oxidation rates of various oxyHb. For low oxygen affinity Hb equilibrated under air, the presence of deoxy subunits accelerates the auto-oxidation. Although a full analysis is complicated, the auto-oxidation studies for air equilibrated samples are more relevant to the development of a blood substitute based on Hb solutions. The double mutants, rHb alpha2beta2 [(C7) F41Y/(G4) N102A] and rHb alpha2beta2 [(C7) F41Y/(E10) K66T], show a lower oxygen affinity and a higher rate of oxidation than Hb A. Simulations of the auto-oxidation rate versus Hb concentration indicate that very high protein concentrations are required to observe the tetramer auto-oxidation rate. Because the dimers oxidize much more rapidly, even a small fraction dimer will influence the observed oxidation rate. 相似文献
163.
Ronald M. A. Knegtel Rasmus H. Fogh Rolf Boelens Robert Kaptein Gunnar Ottleben Heinz Rüterjans Pascal Dumoulin Manfred Schnarr 《Proteins》1995,21(3):226-236
A structural model for the interaction of the LexA repressor DNA binding domain (DBD) with operator DNA is derived by means of Monte Carlo docking. Protein–DNA complexes were generated by docking the LexA repressor DBD NMR solution structure onto both rigid and bent B-DNA structures while giving energy bonuses for contacts in agreement with experimental data. In the resulting complexes, helix III of the LexA repressor DBD is located in the major groove of the DNA and residues Asn-41, Glu-44, and Glu-45 form specific hydrogen bonds with bases of the CTGT DNA sequence. Ser-39, Ala-42, and Asn-41 are involved in a hydrophobic interaction with the methyl group of the first thymine base. Residues in the loop region connecting the two β-sheet strands are involved in nonspecific contacts near the dyad axis of the operator. The contacts observed in the docked complexes cover the entire consensus CTGT half-site DNA operator, thus explaining the specificity of the LexA repressor for such sequences. In addition, a large number of nonspecific interactions between protein and DNA is observed. The agreement between the derived model for the LexA repressor DBD/DNA complex and experimental biochemical results is discussed. © 1995 Wiley-Liss, Inc. 相似文献
164.
Molecular phylogenetics of Stenodermatini bat genera: congruence of data from nuclear and mitochondrial DNA 总被引:2,自引:1,他引:1
Van den Bussche RA; Baker RJ; Wichman HA; Hamilton MJ 《Molecular biology and evolution》1993,10(5):944-959
Within the tribe Stenodermatini the systematics of the complex of species
allied with the genus Artibeus has generated several alternative
phylogenetic hypotheses. The most recent treatment recognized four genera
(Artibeus, Dermanura, Enchisthenes, and Koopmania) and suggested that the
most recent common ancestor of these four genera would include the common
ancestor of all other currently recognized Stenodermatini genera except
Sturnira. To test this hypothesis, we examined an EcoRI-defined nuclear
satellite DNA repeat and 402 bp of DNA sequence variation from the
mitochondrial cytochrome b gene. Phylogenetic conclusions based on Southern
blot analyses, in situ hybridization, and mitochondrial DNA sequence data
indicate that Enchisthenes is not closely related to Dermanura, Artibeus,
or Koopmania and that Dermanura, Artibeus, and Koopmania shared a common
ancestor after diverging from the remainder of the Stenodermatini. If our
conclusions are correct, then justification for recognizing Dermanura and
Koopmania as generically distinct from Artibeus must be based on the
magnitude of difference that distinguishes each rather than on the
conclusion that to place them as congeneric with Artibeus creates a
paraphyletic taxon.
相似文献
165.
John C. M. Dumoulin Johannes L. H. Evers Anton H. J. C. Michiels Math H. E. C. Pieters Marijke Bras Jolande A. Land Joep P. M. Geraedts 《Molecular reproduction and development》1993,36(3):320-327
The effect of various potassium concentrations (ranging from 1.4 mM to 30 mM K+) in modified Tyrode's medium on the culture of mouse zygotes obtained after in vitro fertilization to the blastocyst stage was examined. A clear dose-dependent negative effect of increasing K+ concentrations on the preimplantation embryonic development in vitro was found. We have previously shown that significantly more two-cell embryos reach the blastocyst stage when cultured during the second day postinsemination in medium supplemented with taurine. Because taurine, an amino acid that abounds in the reproductive tract, has been reported to inhibit the enzyme Na+-K+-adenosine triphosphatase (Na+-K+-AT-Pase), we used two other conditions known to inhibit the Na+-K+-ATPase to study their effect on mouse embryo development. Culturing embryos during a short period (the second day postinsemination) in low extracellular K+ concentrations (1.4 mM) or in medium supplemented with ouabain (50 μM) showed positive effects similar to those of culturing in medium with taurine (10 mM). This beneficial effect of ouabain was found in various K+ concentrations tested, including the high concentrations present in the oviduct. Although the effects of low K+ and taurine can possibly be ascribed to their other cellular effects, the effect of ouabain shows that inhibition of the Na+-K+-ATPase during the two-cell stage in the mouse is beneficial for further embryonic development to the blastocyst stage. © 1993 Wiley-Liss, Inc. 相似文献
166.
J P Wolf M T Henriet N U Nguyen G Dumoulin M Laroze S Berthelay 《Comptes rendus des séances de la Société de biologie et de ses filiales》1982,176(5):624-632
In 94 normotensive subjects and free sodium diet, the relationship between SPRA and the 2-hour urinary sodium excretion was significantly better fitted by an hyperbolic function (p less than 0,001); r = 0,53) than a linear one (p less than 0,001; r = -0,31) between SPRA and the 24-hour urinary sodium excretion. (SPRA = Supine Plasma Renin Activity). 相似文献
167.
G Nivaler EA Zimmerman R Defendini AS Liotta DT Kreiger MJ Brownstein 《The Journal of cell biology》1979,81(1):50-58
Adrenocorticotropin and β-lipotropin (β-LPH) have been localized by immunoperoxidase methods in nerve cells and fibers of the hypothalamus and brain stem of the ewe. 6-μm sections were immunostained first for either ACTH or β-LPH. The reaction products and the antibody complexes were then eluted completely from the tissue, and the same section was immunostained for the second peptide. Absorption of the primary antisera with a variety of peptide fragments of ACTH and β-LPH demonstrated, immunocytochemically as well as by radioimmunoassay, that the ACTH and β-LPH antisera were directed to the COOH- and NH(2)-termini of the peptides, respectively. Neither antiserum recognized any portion of the heterologous peptide. In the sequential staining procedure on the same tissue section, preincubation of the antisera with the homologous peptide abolished the staining, whereas preincubation with the heterologous peptide did not affect it, regardless of the order followed. Every nerve cell in the arcuate nucleus that contained ACTH also contained β-LPH, but β-LPH cells appeared, probably falsely, to be twice as numerous as ACTH cells. β-LPH-positive fibers in and beyond the hypothalamus were also more numerous and stained more intensively than ACTH fibers. The salient exception was fibers in the infundibular zona externa, where the opposite was true. Our observations establish that ACTH and β-LPH are contained in the same nerve cells They stongly favor biosynthesis in brain, probably from a common precursor molecule, as has been demonstrated in the pituitary gland. The complexity of the cytologic distribution pattern described suggests that the two peptides are not processed in the same manner by the nerve cell. 相似文献
168.
169.
Cellular oligomerization of alpha-synuclein is determined by the interaction of oxidized catechols with a C-terminal sequence 总被引:1,自引:0,他引:1
Mazzulli JR Armakola M Dumoulin M Parastatidis I Ischiropoulos H 《The Journal of biological chemistry》2007,282(43):31621-31630
The mechanisms that govern the formation of alpha-synuclein (alpha-syn) aggregates are not well understood but are considered a central event in the pathogenesis of Parkinson's disease (PD). A critically important modulator of alpha-syn aggregation in vitro is dopamine and other catechols, which can prevent the formation of alpha-syn aggregates in cell-free and cellular model systems. Despite the profound importance of this interaction for the pathogenesis of PD, the processes by which catechols alter alpha-syn aggregation are unclear. Molecular and biochemical approaches were employed to evaluate the mechanism of catechol-alpha-syn interactions and the effect on inclusion formation. The data show that the intracellular inhibition of alpha-syn aggregation requires the oxidation of catechols and the specific noncovalent interaction of the oxidized catechols with residues (125)YEMPS(129) in the C-terminal region of the protein. Cell-free studies using novel near infrared fluorescence methodology for the detection of covalent protein-ortho-quinone adducts showed that although covalent modification of alpha-syn occurs, this does not affect alpha-syn fibril formation. In addition, oxidized catechols are unable to prevent both thermal and acid-induced protein aggregation as well as fibrils formed from a protein that lacks a YEMPS amino acid sequence, suggesting a specific effect for alpha-syn. These results suggest that inappropriate C-terminal cleavage of alpha-syn, which is known to occur in vivo in PD brain or a decline of intracellular catechol levels might affect disease progression, resulting in accelerated alpha-syn inclusion formation and dopaminergic neurodegeneration. 相似文献
170.
Impacts of yeast metabolic network structure on enzyme evolution 总被引:1,自引:1,他引:0
A comment on D Vitkup, P Kharchenko and A Wagner: Influence of metabolic network structure and function on enzyme evolution. Genome Biol 2006, 7:R39. 相似文献