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31.
Summary A new method, a restrained Monte Carlo (rMC) calculation, is demonstrated for generating high-resolution structures of DNA oligonucleotides in solution from interproton distance restraints and bounds derived from complete relaxation matrix analysis of two-dimensional nuclear Overhauser effect (NOE) spectral peak intensities. As in the case of restrained molecular dynamics (rMD) refinement of structures, the experimental distance restraints and bounds are incorporated as a pseudo-energy term (or penalty function) into the mathematical expression for the molecular energy. However, the use of generalized helical parameters, rather than Cartesian coordinates, to define DNA conformation increases efficiency by decreasing by an order of magnitude the number of parameters needed to describe a conformation and by simplifying the potential energy profile. The Metropolis Monte Carlo method is employed to simulate an annealing process. The rMC method was applied to experimental 2D NOE data from the octamer duplex d(GTA-TAATG)·d(CATTATAC). Using starting structures from different locations in conformational space (e.g. A-DNA and B-DNA), the rMC calculations readily converged, with a root-mean-square deviation (RMSD) of <0.3 Å between structures generated using different protocols and starting structures. Theoretical 2D NOE peak intensities were calculated for the rMC-generated structures using the complete relaxation matrix program CORMA, enabling a comparison with experimental intensities via residual indices. Simulation of the vicinal proton coupling constants was carried out for the structures generated, enabling a comparison with the experimental deoxyribose ring coupling constants, which were not utilized in the structure determination in the case of the rMC simulations. Agreement with experimental 2D NOE and scalar coupling data was good in all cases. The rMC structures are quite similar to that refined by a traditional restrained MD approach (RMSD<0.5 Å) despite the different force fields used and despite the fact that MD refinement was conducted with additional restraints imposed on the endocyclic torsion angles of deoxyriboses. The computational time required for the rMC and rMD calculations is about the same. A comparison of structural parameters is made and some limitations of both methods are discussed with regard to the average nature of the experimental restraints used in the refinement.Abbreviations MC
Monte Carlo
- rMC
restrained Monte Carlo
- MD
molecular dynamics
- rMD
restrained molecular dynamics
- DG
distance geometry
- EM
energy minimization
- 2D NOE
two-dimensional nuclear Overhauser effect
- DQF-COSY
double-quantum-filtered correlation spectroscopy
- RMSD
root-mean-square deviation
To whom correspondence should be addressed. 相似文献
32.
T. Keller E. Frey R. Heil S. Rietschel S. Schaal M. Schmitz 《Pal?ontologische Zeitschrift》1991,65(1-2):221-224
The “Framework Messel” formulates regulations, recommendations and instructions for planning and carrying out palaeontological excavations in the Messel pit. The excavation of fossils in the Land Hessen is to some extent controlled by the Monument Protection Law. Therefore, the Framework was developed in close cooperation with the Land Monument Office. Administrative, scientific and organizational conditions for the excavations in the Middle Eocene oil-shales of Messel are listed. Instructional pamphlets explain technical details regarding methods of documentation, excavation and preparation of finds and results. 相似文献
33.
A receptor for protein import into potato mitochondria 总被引:3,自引:0,他引:3
Five potential surface receptors for protein import into plant mitochondria were identified by gentle trypsin treatment of intact mitochondria from potato tubers and subsequent preparation of outer mitochondrial membranes. One of them, a 23 kDa protein, was purified to homogeneity and analysed by direct protein sequencing. Copy DNA clones encoding the corresponding polypeptide were isolated with labelled oligonucleotides derived from the amino acid data. The 23 kDa protein shares significant sequence similarity with protein import receptors from fungal mitochondria and contains one of their typical tetratricopeptide motifs. Its integration into the outer membrane is independent of protease accessible surface receptors and not accompanied by proteolytic processing. Monospecific antibodies against the 23 kDa protein significantly reduce import capacity of isolated mitochondria indicating that this component is indeed involved in the recognition or import of precursor proteins. As in fungi, immunological inhibition of protein import with IgGs against a single receptor is incomplete suggesting the existence of other receptors in the outer mitochondrial membrane of plant mitochondria. 相似文献
34.
Marc Pauly Isabelle Kayser Martine Schmitz Fernand Ries François Hentges Mario Dicato 《Journal of molecular evolution》1995,41(6):974-978
The mdr1 gene, first member of the human multidrug-resistance gene family, is a major gene involved in cellular resistance to several drugs used in anticancer chemotherapy. Its product, the drug-excreting P-glycoprotein, shows a bipartite structure formed by two similar adjacent halves. According to one hypothesis, the fusion of two related ancestral genes during evolution could have resulted in this structure. The DNA sequence analysis of the introns located in the region connecting the two halves of the human mdr1 gene revealed a highly conserved poly(CA) · poly (TG) sequence in intron 15 and repeated sequences of the Alu family in introns 14 and 17. These repeated sequences most likely represent molecular fossils of ancient DNA elements which were involved in such a recombination event.
Correspondence to: M. Pauly 相似文献
35.
A. L. Archibald C. S. Haley J. F. Brown S. Couperwhite H. A. McQueen D. Nicholson W. Coppieters A. Van de Weghe A. Stratil A. K. Winterø M. Fredholm N. J. Larsen V. H. Nielsen D. Milan N. Woloszyn A. Robic M. Dalens J. Riquet J. Gellin J. -C. Caritez G. Burgaud L. Ollivier J. -P. Bidanel M. Vaiman C. Renard H. Geldermann R. Davoli D. Ruyter E. J. M. Verstege M. A. M. Groenen W. Davies B. Høyheim A. Keiserud L. Andersson H. Ellegren M. Johansson L. Marklund J. R. Miller D. V. Anderson Dear E. Signer A. J. Jeffreys C. Moran P. Le Tissier Muladno M. F. Rothschild C. K. Tuggle D. Vaske J. Helm H. -C. Liu A. Rahman T. -P. Yu R. G. Larson C. B. Schmitz 《Mammalian genome》1995,6(3):157-175
A linkage map of the porcine genome has been developed by segregation analysis of 239 genetic markers. Eighty-one of these markers correspond to known genes. Linkage groups have been assigned to all 18 autosomes plus the X Chromosome (Chr). As 69 of the markers on the linkage map have also been mapped physically (by others), there is significant integration of linkage and physical map data. Six informative markers failed to show linkage to these maps. As in other species, the genetic map of the heterogametic sex (male) was significantly shorter (16.5 Morgans) than the genetic map of the homogametic sex (female) (21.5 Morgans). The sex-averaged genetic map of the pig was estimated to be 18 Morgans in length. Mapping information for 61 Type I loci (genes) enhances the contribution of the pig gene map to comparative gene mapping. Because the linkage map incorporates both highly polymorphic Type II loci, predominantly microsatellites, and Type I loci, it will be useful both for large experiments to map quantitative trait loci and for the subsequent isolation of trait genes following a comparative and candidate gene approach. 相似文献
36.
A. Schmitz A. Oustry B. Chaput I. Bahri-Darwich M. Yerle D. Millan G. Frelat E. P. Cribiu 《Mammalian genome》1995,6(6):415-420
A bovine bivariate flow karyotype has been established from a primary fibroblast cell culture carrying a 4;10 Robertsonian translocation. From 27 to 36 populations could be resolved by flow cytometry although the anticipated number was 31. Separation of chromosomal pairs into two populations explains this high resolution and confirms the high level of heteromorphism previously observed. We used a PARM-PCR (Priming Autorizing Random Mismatches) procedure for the production of paint probes from flow-sorted chromosome fractions. These probes were used for chromosome identification by fluorescence in situ hybridization (FISH) on R-banded metaphase spreads. We present the localization of all the bovine chromosome types on the flow karyotype. Twenty-two chromosome types including the translocated chromosome were sorted as pure fractions. 相似文献
37.
The N-terminal extension of the ADP/ATP translocator is not involved in targeting to plant mitochondria in vivo 总被引:4,自引:1,他引:3
Teresa Mozo Karsten Fischer Ulf Ingo Flügge Udo Klaus Schmitz 《The Plant journal : for cell and molecular biology》1995,7(6):1015-1020
The mitochondrial ADP/ATP translocator, also called adenine nucleotide translocase (ANT), is synthesized in plants with an N-terminal extension which is cleaved upon import into mitochondria. In contrast, the homologous proteins of mammals or fungi do not contain such a transient amino terminal presequence. To investigate whether the N-terminal extension is needed for correct intracellular sorting in vivo , translational fusions were constructed of the translocator cDNA—with and without presequence—with the β-glucuronidase ( gus ) reporter gene. The distribution of reporter enzymatic activity in the subcellular compartments of transgenic plants and transformed yeast cells was subsequently analysed. The results show that: (i) the plant translocator presequence is not necessary for the correct localization of the ANT to the mitochondria; (ii) the mitochondrial targeting information contained in the mature part of the protein is sufficient to overcome, to some extent, the presence of plastid transit peptides; and (iii) the presequence alone is not able to target a passenger protein to mitochondria in vivo . 相似文献
38.
A comparison of enzyme-immunoassay and radioimmunoassay for detection of hepatitis A virus and antibodies against hepatitis A virus 总被引:1,自引:0,他引:1
A direct comparison has been made of tracers labelled with an enzyme and with 125I in solid phase enzyme-immunoassay (EIA) and solid phase radioimmunoassay (RIA) for the detection of hepatitis A virus (HAV) antigen and antibodies to HAV. By comparing the binding capacity of peroxidase-labelled anti-HAV-IgG and anti-HAV-F(ab)2 fragments tracers, anti-HAV-IgG was found to have a higher binding capacity than anti-HAV-F(ab)2 fragments in both EIA and RIA. For EIA 16.25-fold more anti-HAV-IgG was needed for one test probe compared to RIA and 32.5-fold more anti-HAV-F(ab)2 fragments. For the detection of HAV antigen from stool preparations and IgG and IgM antibodies against HAV, there were only minor quantitative differences in titre. EIA was as sensitive as RIA. 相似文献
39.
From 70 patients 68.3 +/- 10.1 years of age, 260 sputum specimens containing various acellular bodies were evaluated. This corresponded to 1% of all sputum specimens examined. The round to oval bodies were mostly concentrically structured and displayed different, partly amorphous, partly crystalline components. The periodic acid-Schiff stain was usually positive in these smears, 52% of which contained birefringent bodies. The average diameter was 25 +/- 10.9 micron. While intersample and intrasample frequencies of such bodies were extremely variable, a correlation with an increased number of Curschmann spirals and the degree of inflammation was observed (P less than 0.02). There was a correlation with neither sex, smoking habits nor most types of cancer. A positive correlation existed with chronic obstructive bronchitis, cor pulmonale, obstructive pulmonary diseases and one case of adenocarcinoma of the lung. This finding was confirmed by eight of ten new cases. The formation of the bodies can be intraalveolar, comparable to microliths, in the bronchial glands, corresponding to sialiths, and by intrabronchial mucus condensation, eventually around structures serving as cores. Changing frequencies in repeat investigations demonstrated a presumably rapid formation. 相似文献
40.
Genetic studies of the lac repressor. IX. Generation of altered proteins by the suppression of nonsence mutations. 总被引:18,自引:0,他引:18
J H Miller C Coulondre M Hofer U Schmeissner H Sommer A Schmitz P Lu 《Journal of molecular biology》1979,131(2):191-222
We have generated more than 300 altered lac repressor proteins carrying known amino acid replacements, by employing nonsense mutations at 90 positions in the lacI gene together with eight different nonsense suppressors. This allows the substitution of lysine, serine, tyrosine, leucine and glutamine at virtually all of the respective positions in the repressor, and tryptophan at ten positions in the repressor. Since most of the nonsense sites have been correlated with specific codons in the lacI messenger RNA, in almost all cases the position of the substituted residue is known. This process results in the creation of a large number of mutant phenotypes. We have analyzed the effects of each substitution in vivo, and in several cases studied partially purified repressors in vitro. The properties of the altered proteins have been compared with the position and nature of each exchanged residue. We discuss the implications of these findings with regard to repressor structure in particular, and to protein structure in general. Further applications of the suppression method are also considered. 相似文献