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941.
Pathways of apoptosis and importance in development 总被引:4,自引:0,他引:4
The elimination of cells by programmed cell death is a fundamental event in development where multicellular organisms regulate cell numbers or eliminate cells that are functionally redundant or potentially detrimental to the organism. The evolutionary conservation of the biochemical and genetic regulation of programmed cell death across species has allowed the genetic pathways of programmed cell death determined in lower species, such as the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster to act as models to delineate the genetics and regulation of cell death in mammalian cells. These studies have identified cell autonomous and non-autonomous mechanisms that regulate of cell death and reveal that developmental cell death can either be a pre-determined cell fate or the consequence of insufficient cell interactions that normally promote cell survival. 相似文献
942.
Triple resonance HN(COCA)NH pulse sequences for correlating 1H(i), 15N(i),1H(i-1), and 15N(i-1) spins that utilize overlapping coherence transfer periods provide increased sensitivityrelative to pulse sequences that utilize sequential coherence transfer periods. Although theoverlapping sequence elements reduce the overall duration of the pulse sequences, theprincipal benefit derives from a reduction in the number of 180° pulses. Two versions of thetechnique are presented: a 3D (H)N(COCA)NH experiment that correlates 15N(i),1H(i-1), and 15N(i-1) spins, and a 3D HN(COCA)NH experiment that correlates 1H(i), 15N(i),1H(i-1), and 15N(i-1) spins by simultaneously encoding the 1H(i) and 15N(i) chemical shiftsduring the t1 evolution period. The methods are demonstrated on a 13C/15N-enriched sampleof the protein ubiquitin and are easily adapted for application to 2H/13C/15N-enrichedproteins. 相似文献
943.
C. E. Bell T. O. Yeates D. Eisenberg 《Protein science : a publication of the Protein Society》1997,6(10):2084-2096
The conformation of NAD bound to diphtheria toxin (DT), an ADP-ribosylating enzyme, has been compared to the conformations of NAD(P) bound to 23 distinct NAD(P)-binding oxidoreductase enzymes, whose structures are available in the Brookhaven Protein Data Bank. For the oxidoreductase enzymes, NAD(P) functions as a cofactor in electron transfer, whereas for DT, NAD is a labile substrate in which the N-glycosidic bond between the nicotinamide ring and the N-ribose is cleaved. All NAD(P) conformations were compared by (1) visual inspection of superimposed molecules, (2) RMSD of atomic positions, (3) principal component analysis, and (4) analysis of torsion angles and other conformational parameters. Whereas the majority of oxidoreductase-bound NAD(P) conformations are found to be similar, the conformation of NAD bound to DT is found to be unusual. Distinctive features of the conformation of NAD bound to DT that may be relevant to DT''s function as an ADP-ribosylating enzyme include (1) an unusually short distance between the PN and N1N atoms, reflecting a highly folded conformation for the nicotinamide mononucleotide (NMN) portion of NAD, and (2) a torsion angle chi N approximately 0 degree about the scissile N-glycosidic bond, placing the nicotinamide ring outside of the preferred anti and syn orientations. In NAD bound to DT, the highly folded NMN conformation and torsion angle chi N approximately 0 degree could contribute to catalysis, possibly by orienting the C1''N atom of NAD for nucleophilic attack, or by placing strain on the N-glycosidic bond, which is cleaved by DT. The unusual overall conformation of NAD bound to DT is likely to reflect the structure of DT, which is unusual among NAD(P)-binding enzymes. In DT, the NAD binding site is formed at the junction of two antiparallel beta-sheets. In contrast, although the 24 oxidoreductase enzymes belong to at least six different structural classes, almost all of them bind NAD(P) at the C-terminal end of a parallel beta-sheet. The structural alignments and principal component analysis show that enzymes of the same structural class bind to particularly similar conformations of NAD(P), with few exceptions. The conformation of NAD bound to DT superimposes closely with that of an NAD analogue bound to Pseudomonas exotoxin A, an ADP-ribosylating toxin that is structurally homologous to DT. This suggests that all of the ADP-ribosylating enzymes that are structurally homologous to DT and ETA will bind a highly similar conformation of NAD. 相似文献
944.
Karianne Johansen Mette Krogh Knut E. Rasmussen 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1997,690(1-2):223-231
Problems related to interaction of drugs with the dialysis membrane and to protein binding must be overcome in order to develop automated methods for drug analysis based on on-line dialysis, trace enrichment and HPLC. In order to study these problems, clozapine and its active metabolite N-desmethylclozapine were chosen as model compounds because they were found to interact with the dialysis membrane, and clozapine is highly protein bound. Addition of a cationic surfactant, dodecylethyldimethyl ammonium bromide, to the donor solution and to the plasma samples was found to inhibit interaction of the drugs with surfaces. The protein binding in plasma was disrupted prior to dialysis by lowering the pH with hydrochloric acid and the plasma proteins were solubilised with glycerol. The results obtained were used to develop a fully automated method for the determination of clozapine and N-desmethylclozapine in human plasma. More than 100 samples could be analysed within 24 h. The limit of detection in human plasma was 0.050 μmol/1 for clozapine and 0.055 μmol/1 for N-desmethylclozapine. Linearity was found for drug concentrations between 0.25–3 μmol/1. The relative standard deviations were between 1.2–6.7% and the method was applicable for therapeutic drug monitoring. 相似文献
945.
The mechanism for energy and signal transport in proteins as suggested by Davydov is discussed. The idea is based on a coupling of amide-I oscillators to acoustic phonons in a hydrogen bonded chain. Results as obtained with the usually used ansätze are discussed. The quality of these states for an approximate solution of the time-dependent Schrödinger equation is investigated. It is found that the semiclassical ansatz is a poor approximation, while the more sophisticated |D1> state seems to represent the exact dynamics quite well. This was shown by extensive calculations, both analytically and numerically in the two preceding papers. Calculations at a temperature of 300K for one chain, as well as for three coupled ones (as they are present in an -helix) are presented and discussed. From the calculations it is evident, that Davydov solitons are stable for reasonable parameter values at 300K for special initial excitations close to the terminal sites of the chain. Further vibrational spectra are presented and discussed. Our results suggest, that due to their strong dependence on the initial state, the Davydov |D1> model system might be a (quantum) chaotic one. 相似文献
946.
Stephan I. Dimitrov Vladimir L. Makarov Lyuben N. Marekov Beltcho G. Beltchev 《International journal of biological macromolecules》1985,7(2):122-124
In this study we attempt to differentiate between the effects of the non-histone chromosomal proteins and histone H1 on the structure of the nucleosomes and the chromatin fibre in solution. The properties of chromatin preparations with different histone H1 and non-histone protein compositions were compared using circular dichroism and flow linear dichroism and the following conclusions were drawn. When histone H1 is absent the non-histone proteins partially prevent the unfolding of the nucleosomes at low ionic strength. The complete blocking of this unfolding, however, is accomplished only in the presence of histone H1. The non-histone proteins do not affect the orientation of the nucleosomes along the fibre axis. Only histone H1 can maintain the positive anisotropy of the chromatin fibre. 相似文献
947.
948.
E. N. Trifonov 《Journal of molecular evolution》1994,38(5):543-546
Since 1929 the concept that proteins are built from subunits of certain standard size (Svedberg 1929) has been revisited several
times, each time with a new demonstration that, indeed, there are certain preferred protein sizes. According to recent estimates
the overrepresented sizes are close to multiples of 125 amino acid (aa) residues for eukaryotes and 150 residues for prokaryotes.
To explain these preferences, a hypothesis is suggested, and quantitatively developed, on the recombinational nature of this
regularity. The protein-coding sequences are assumed to evolve at some early stage via recombinational events—insertions of
DNA circles of a certain optimal size. The contour lengths of the protein-coding DNA circles had to be simultaneously divisible
by three and, to minimize torsional constraint, by the DNA helical repeat. With these two conditions satisfied, the calculated
contour lengths of the DNA circles, 250–500 base pairs (bp), turn out to correspond well to known optimal DNA circularization
sizes and to the predicted range of the protein sequence subunit sizes: 80–170 as residues, which covers experimentally observed
values. The subunit size is found to be strongly influenced by the helical repeat of DNA. The sizes 125 and 150 as are derived
when the corresponding helical repeats of DNA are set within fractions of promilles from the 10.54 by/turn value. This fits
to the experimentally estimated mean for natural mixed DNA sequences, 10.53–10.57 by/turn. The suggested recombinational mechanism
thus not only gives a qualitative explanation for the observed underlying order in the protein sequences but also quantitatively
links the observed protein sequence sizes with the optimal DNA circularization size and with the helical repeat of DNA. It
also offers a versatile molecular model of early protein evolution by fusion and insertion of preexisting proteins of standard
subunit sizes. 相似文献
949.
Summary The use of chemoselective ligation methods and orthogonal protection techniques allows access to Template-Assembled Synthetic Protein (TASP) molecules exhibiting a large variety of packing topologies. This is demonstrated for the synthesis of an antiparallel 4-helical bundle TASP by condensing amphiphilic peptide blocks, containing aldehyde functions at the C- or N-terminus, to a selectively addressable topological template via oxime bond formation. The resulting antiparallel 4-helix TASP is obtained in high yield and shows a template-induced helical conformation. 相似文献
950.
Vola R. Lombardi A. Tarditi L. Zaccolo M. Neri D. Björck L. Mariani M. 《Cell biochemistry and biophysics》1994,24(1-3):27-36
Several bacterial cell wall proteins, like proteins A and G, with valuable affinity for immunoglobulins have been discovered
and are currently employed in immunological techniques. In 1988, protein L, a bacterial cell wall protein with Ig-binding
capacity, was isolated from the anaerobic bacterial speciesPeptostreptococcus magnus. Binding data with immunoglobulin fragments suggested that protein L could selectively bind the variable region of human
kappa light chains. More recently a recombinant LG fusion protein was expressed inE. coli containing four repeated Ig-binding domains of protein L (fragment B1–4) and two IgG Fc-binding protein G domains (fragment
CDC). Recombinant L and LG proteins were tested in the purification of murine monoclonal IgG and their fragments. After affinity-constant
evaluation in different buffer systems, high-pressure affinity-chromatography columns were prepared by coupling the proteins
to Affi-prep 10 resin and tested with eight different murine monoclonal antibodies and their fragments of various isotypes.
Affinity-chromatography experiments confirming radioimmunoassay results showed 75% fragment-binding capacity of protein L
and 100% of protein LG. These results evidenced protein LG as the most powerful Ig-binding tool so far described. Therefore,
application of these proteins may be suggested in the purification of murine immunoglobulins and their fragments, including
the engineered ones. 相似文献