排序方式: 共有33条查询结果,搜索用时 15 毫秒
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Jean-Marie LEHN 《复旦学报(自然科学版)》2007,(5)
1 Results Animate as well as inanimate matter,living organisms as well as materials,are formed of molecules and of the organized entities resulting from the interaction of molecules with each other.Chemistry provides the bridge between the molecules of inanimate matter and the highly complex molecular architectures and systems which make up living organisms. Synthetic chemistry has developed a very powerful set of methods for constructing ever more complex molecules.Supramolecular chemistry seeks to con... 相似文献
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Jean-Paul Mornon Pierre Lehn Isabelle Callebaut 《Cellular and molecular life sciences : CMLS》2009,66(21):3469-3486
Cystic fibrosis transmembrane conductance regulator (CFTR), involved in cystic fibrosis (CF), is a chloride channel belonging
to the ATP-binding cassette (ABC) superfamily. Using the experimental structure of Sav1866 as template, we previously modeled
the human CFTR structure, including membrane-spanning domains (MSD) and nucleotide-binding domains (NBD), in an outward-facing
conformation (open channel state). Here, we constructed a model of the CFTR inward-facing conformation (closed channel) on
the basis of the recent corrected structures of MsbA and compared the structural features of those two states of the channel.
Interestingly, the MSD:NBD coupling interfaces including F508 (ΔF508 being the most common CF mutation) are mainly left unchanged.
This prediction, completed by the modeling of the regulatory R domain, is supported by experimental data and provides a molecular
basis for a better understanding of the functioning of CFTR, especially of the structural features that make CFTR the unique
channel among the ABC transporters. 相似文献
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Isabelle Callebaut Brice Hoffmann Pierre Lehn Jean-Paul Mornon 《Cellular and molecular life sciences : CMLS》2017,74(1):3-22
The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a member of the ATP-binding cassette (ABC) transporter superfamily that functions as an ATP-gated channel. Considerable progress has been made over the last years in the understanding of the molecular basis of the CFTR functions, as well as dysfunctions causing the common genetic disease cystic fibrosis (CF). This review provides a global overview of the theoretical studies that have been performed so far, especially molecular modelling and molecular dynamics (MD) simulations. A special emphasis is placed on the CFTR-specific evolution of an ABC transporter framework towards a channel function, as well as on the understanding of the effects of disease-causing mutations and their specific modulation. This in silico work should help structure-based drug discovery and design, with a view to develop CFTR-specific pharmacotherapeutic approaches for the treatment of CF in the context of precision medicine. 相似文献
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Steinberg KM Antonacci F Sudmant PH Kidd JM Campbell CD Vives L Malig M Scheinfeldt L Beggs W Ibrahim M Lema G Nyambo TB Omar SA Bodo JM Froment A Donnelly MP Kidd KK Tishkoff SA Eichler EE 《Nature genetics》2012,44(8):872-880
The 17q21.31 inversion polymorphism exists either as direct (H1) or inverted (H2) haplotypes with differential predispositions to disease and selection. We investigated its genetic diversity in 2,700 individuals, with an emphasis on African populations. We characterize eight structural haplotypes due to complex rearrangements that vary in size from 1.08-1.49 Mb and provide evidence for a 30-kb H1-H2 double recombination event. We show that recurrent partial duplications of the KANSL1 gene have occurred on both the H1 and H2 haplotypes and have risen to high frequency in European populations. We identify a likely ancestral H2 haplotype (H2') lacking these duplications that is enriched among African hunter-gatherer groups yet essentially absent from West African populations. Whereas H1 and H2 segmental duplications arose independently and before human migration out of Africa, they have reached high frequencies recently among Europeans, either because of extraordinary genetic drift or selective sweeps. 相似文献
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Rabia?Sarroukh Emilie?Cerf Sylvie?Derclaye Yves?F.?Dufrêne Erik?Goormaghtigh Jean-Marie?RuysschaertEmail author Vincent?Raussens 《Cellular and molecular life sciences : CMLS》2011,68(8):1429-1438
Alzheimer’s disease (AD) is a neurodegenerative disorder occurring in the elderly. It is widely accepted that the amyloid
beta peptide (Aβ) aggregation and especially the oligomeric states rather than fibrils are involved in AD onset. We used infrared
spectroscopy to provide structural information on the entire aggregation pathway of Aβ(1–40), starting from monomeric Aβ to
the end of the process, fibrils. Our structural study suggests that conversion of oligomers into fibrils results from a transition
from antiparallel to parallel β-sheet. These structural changes are described in terms of H-bonding rupture/formation, β-strands
reorientation and β-sheet elongation. As antiparallel β-sheet structure is also observed for other amyloidogenic proteins
forming oligomers, reorganization of the β-sheet implicating a reorientation of β-strands could be a generic mechanism determining
the kinetics of protein misfolding. Elucidation of the process driving aggregation, including structural transitions, could
be essential in a search for therapies inhibiting aggregation or disrupting aggregates. 相似文献
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Dujon B Sherman D Fischer G Durrens P Casaregola S Lafontaine I De Montigny J Marck C Neuvéglise C Talla E Goffard N Frangeul L Aigle M Anthouard V Babour A Barbe V Barnay S Blanchin S Beckerich JM Beyne E Bleykasten C Boisramé A Boyer J Cattolico L Confanioleri F De Daruvar A Despons L Fabre E Fairhead C Ferry-Dumazet H Groppi A Hantraye F Hennequin C Jauniaux N Joyet P Kachouri R Kerrest A Koszul R Lemaire M Lesur I Ma L Muller H Nicaud JM Nikolski M Oztas S Ozier-Kalogeropoulos O Pellenz S 《Nature》2004,430(6995):35-44
Identifying the mechanisms of eukaryotic genome evolution by comparative genomics is often complicated by the multiplicity of events that have taken place throughout the history of individual lineages, leaving only distorted and superimposed traces in the genome of each living organism. The hemiascomycete yeasts, with their compact genomes, similar lifestyle and distinct sexual and physiological properties, provide a unique opportunity to explore such mechanisms. We present here the complete, assembled genome sequences of four yeast species, selected to represent a broad evolutionary range within a single eukaryotic phylum, that after analysis proved to be molecularly as diverse as the entire phylum of chordates. A total of approximately 24,200 novel genes were identified, the translation products of which were classified together with Saccharomyces cerevisiae proteins into about 4,700 families, forming the basis for interspecific comparisons. Analysis of chromosome maps and genome redundancies reveal that the different yeast lineages have evolved through a marked interplay between several distinct molecular mechanisms, including tandem gene repeat formation, segmental duplication, a massive genome duplication and extensive gene loss. 相似文献
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Manfred F. R. Kets De Vries Danny Miller Jean-Marie Toulouse Peter H. Friesen Maurice Boisvert Roland Theriault 《Journal of forecasting》1984,3(2):161-172
It was hypothesized that there are important non-linear life-cycle influences upon job and organizational satisfaction. Five common life-cycle stages were identified from the literature: the phases of ‘reality shock’, ‘socialization and growth’, ‘mid-career crisis’, ‘acceptance’, and ‘pre-retirement’. The first, third and last stages were expected to show declines in job and organizational satisfaction because of the personal and job-related disappointments and crises that typically occur during these periods of life. The second and fourth stages were expected to show increases in satisfaction because of the pleasant life experiences that often occur then. All but the first stage supported these hypotheses when we controlled for the influence of sex, education, job experience, level in the hierarchy and occupational upward mobility. 相似文献
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Nucleic acids, because of their key biological role, are prime targets for the design of either analogues that may mimic some of their features or of complementary ligands that may selectively bind to and react with them for regulation or reaction. Whereas there has been much work on the latter topic since the elucidation of the double-helical structure of DNA, comparatively little has been done on structural and/or functional models, probably owing to the lack of self-organizing molecular systems. Here we present a class of artificial systems, the nucleohelicates, which are of interest from both points of view because they combine the double-helical structure of the double-stranded metal complexes, the helicates, with the selective interaction features of nucleic-acid bases. These functionalized species allow the study of structural effects on the formation of the double helix and on the binding to other entities, in particular to nucleic acids. 相似文献