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991.
Wildling L Rankl C Haselgrübler T Gruber HJ Holy M Newman AH Zou MF Zhu R Freissmuth M Sitte HH Hinterdorfer P 《The Journal of biological chemistry》2012,287(1):105-113
The serotonin transporter (SERT) terminates neurotransmission by removing serotonin from the synaptic cleft. In addition, it is the site of action of antidepressants (which block the transporter) and of amphetamines (which induce substrate efflux). The interaction energies involved in binding of such compounds to the transporter are unknown. Here, we used atomic force microscopy (AFM) to probe single molecular interactions between the serotonin transporter and MFZ2-12 (a potent cocaine analog) in living CHOK1 cells. For the AFM measurements, MFZ2-12 was immobilized on AFM tips by using a heterobifunctional cross-linker. By varying the pulling velocity in force distance cycles drug-transporter complexes were ruptured at different force loadings allowing for mapping of the interaction energy landscape. We derived chemical rate constants from these recordings and compared them with those inferred from inhibition of transport and ligand binding: koff values were in good agreement with those derived from uptake experiments; in contrast, the kon values were scaled down when determined by AFM. Our observations generated new insights into the energy landscape of the interaction between SERT and inhibitors. They thus provide a useful framework for molecular dynamics simulations by exploring the range of forces and energies that operate during the binding reaction. 相似文献
992.
Solid-state Nuclear Magnetic Resonance can provide detailed insight into structural and dynamical aspects of complex biomolecules.
With increasing molecular size, advanced approaches for spectral simplification and the detection of medium to long-range
contacts become of critical relevance. We have analyzed the protonation pattern of a membrane-embedded ion channel that was
obtained from bacterial expression using protonated precursors and D2O medium. We find an overall reduction of 50% in protein protonation. High levels of deuteration at Hα and Hβ positions reduce spectral congestion in (1H,13C,15N) correlation experiments and generate a transfer profile in longitudinal mixing schemes that can be tuned to specific resonance
frequencies. At the same time, residual protons are predominantly found at amino-acid side-chain positions enhancing the prospects
for obtaining side-chain resonance assignments and for detecting medium to long-range contacts. Fractional deuteration thus
provides a powerful means to aid the structural analysis of complex biomolecules by solid-state NMR. 相似文献
993.
Kurtoğlu S Sen B Melikoğlu G Becker H Zapp J Kiemer AK Meriçli F Meriçli AH 《Zeitschrift für Naturforschung. C, Journal of biosciences》2012,67(3-4):103-107
From the roots of Aconitum vulparia Rchb., collected in Prüm (Germany), a new norditerpenoid alkaloid, named alexhumboldtine, has been isolated along with the known norditerpenoid alkaloids lappaconitine, anthranoyllycoctonine, lycoctonine, puberaconitine, ajacine, and septentriodine. The structure of alexhumboldtine was established on the basis of 1H, 13C, DEPT, homonuclear 1H COSY, NOESY, HSQC, and HMBC NMR studies. From the aerial parts of the plant another norditerpenoid alkaloid, aconorine, has been isolated. 相似文献
994.
Simone?RiehlEmail author Marion?Benz Nicholas?J.?Conard Hojjat?Darabi Katleen?Deckers Hassan?Fazeli?Nashli Mohsen?Zeidi-Kulehparcheh 《Vegetation History and Archaeobotany》2012,21(2):95-106
The beginnings of agriculture throughout the Fertile Crescent are still not completely understood, particularly at the eastern end of the Fertile Crescent in the area of modern Iran. Archaeobotanical samples from Epipalaeolithic/PPNA Körtik Tepe in southeastern Turkey and from the Pre-Pottery Neolithic sites of Chogha Golan and East Chia Sabz in south western Iran were studied in order to define the status of cultivation at these sites. Preliminary results show the presence of abundant wild progenitor species of crops at the Iranian sites before 10600 cal. b.p., and very few wild progenitor species at Körtik Tepe dated to 11700–11250 cal. b.p. The Iranian sites also indicate size increase of wild barley grain across a sequence of 400 years through either cultivation or changing moisture conditions. 相似文献
995.
Meghan Avolio Tobias Müller Anja Mpangara Michael Fitz Ben Becker Alexander Pauck Anja Kirsch Daniel Wipf 《Mycorrhiza》2012,22(7):515-524
Nitrogen (N) utilization by ectomycorrhizal fungi is an essential aspect of their ecosystem function. N deposition changes both the N pools and the carbon/nitrogen (C/N) ratio of the substrates where ectomycorrhizal fungi are found, and it is important to understand how these changes affect the N forms used by ectomycorrhizal fungi. To overcome the difficulties of studying ectomycorrhizal fungi in situ, we investigated all known N genes in the model fungus, Hebeloma cylindrosporum in a culture study. In addition to studying the regulation of all known N utilization genes, we aimed to understand whether there are gene clusters that undergo similar regulation. Lastly we studied how C/N ratio, N transporter type, and N source affected relative gene expression levels. We grew the D2 strain of H. cylindrosporum on a range of inorganic and organic N sources under low, medium, and high C/N ratios. We found three gene clusters that were regulated in a similar pattern. Lastly, we found C/N ratio, N source and N transporter type all affected gene expression levels. Relative expression levels were highest on the high C/N ratio, BSA and diLeucine N sources, and inorganic N transporters were always expressed at higher levels than organic N transporters. These results suggest that inorganic N sources may always the default preference for H. cylindrosporum, regardless of both the N sources and the C/N ratio of the substrate. 相似文献
996.
997.
Mittapalli GK Vellucci D Yang J Toussaint M Brothers SP Wahlestedt C Roberts E 《Bioorganic & medicinal chemistry letters》2012,22(12):3916-3920
Highly potent and selective small molecule neuropeptide Y Y2 receptor antagonists are reported. The systematic SAR exploration of a hit molecule N-(4-ethoxyphenyl)-4-[hydroxy(diphenyl)methyl]piperidine-1-carbothioamide, identified from HTS, led to the discovery of highly potent NPY Y2 antagonists 16 (CYM 9484) and 54 (CYM 9552) with IC(50) values of 19 nM and 12 nM respectively. 相似文献
998.
Koromiko [Hebe salicifolia G. Forst. (Pennell)] is a woody angiosperm native to New Zealand and Chile. Hebe spp. belong to the otherwise herbaceous family Plantaginaceae in the order Lamiales. Reaction wood exerting expansional forces
was found on the lower side of leaning H. salicifolia stems. Such reaction wood is atypical for angiosperms, which commonly form contracting reaction wood on the upper side of
leaning stems. Reaction wood typical for angiosperms is formed by species in other families in the order Lamiales. This suggests
that the form of reaction wood is specific to the family level. Functionally the reaction wood of H. salicifolia is similar to that found in gymnosperms, which both act by pushing. However, their chemical, anatomical and physical characteristics
are different. Typical features of reaction wood present in gymnosperms such as high density, thick-walled rounded cells and
the presence of (1 → 4)-β-galactan in the secondary cell wall layer are absent in H. salicifolia reaction wood. Reaction wood of H. salicifolia varies from normal wood in having a higher microfibril angle, which is likely to determine the direction of generated maturation
stresses. 相似文献
999.