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71.
2-Ethynylnaphthalene (2EN) is an effective mechanism-based inhibitor of CYP2B4. There are two inhibitory components: (1) irreversible inactivation of CYP2B4 (a typical time-dependent inactivation), and (2) a reversible component. The reversible component was unusual in that the degree of inhibition was not simply a characteristic of the enzyme-inhibitor interaction, but dependent on the size of the substrate molecule used to monitor residual activity. The effect of 2EN on the metabolism of seven CYP2B4 substrates showed that it was not an effective reversible inhibitor of substrates containing a single aromatic ring; substrates with two fused rings were competitively inhibited by 2EN; and larger substrates were non-competitively inhibited. Energy-based docking studies demonstrated that, with increasing substrate size, the energy of 2EN and substrate co-binding in the active site became unfavorable precisely at the point where 2EN became a competitive inhibitor. Hierarchical docking revealed potential allosteric inhibition sites separate from the substrate binding site. 相似文献
72.
2-Ethynylnaphthalene (2EN) is a mechanism-based inhibitor of CYP2B4 with two components to the inhibition, (1) enzyme inactivation, which requires covalent binding of the 2EN metabolite, and (2) reversible inhibition by 2EN itself. Both inhibitory components were examined using several different CYP2B4 substrates. Preincubation of CYP2B4 with 2EN led to a time-dependent inactivation of each of the CYP2B4-dependent activities examined; however, the ability of 2EN to reversibly inhibit CYP2B4 depended on the substrate employed, which is inconsistent with classical inhibition patterns. The degree 2EN's reversible inhibition was shown not to correlate with the substrate affinity for the active site, but with parameters related to the molecular size of the substrate. The results are consistent with 2EN and the smaller substrates simultaneously fitting in the CYP2B4 active site, leading to very little inhibition. Larger substrates exhibited greater degrees of inhibition because of their inability to co-bind with inhibitor in the active site. 相似文献
73.
The Horn of Africa as a centre of barley diversification and a potential domestication site 总被引:2,自引:1,他引:1
Orabi J Backes G Wolday A Yahyaoui A Jahoor A 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2007,114(6):1117-1127
According to a widely accepted theory on barley domestication, wild barley (Hordeum vulgare ssp. spontaneum) from the Fertile Crescent is the progenitor of all cultivated barley (H. vulgare ssp. vulgare). To determine whether barley has undergone one or more domestication events, barley accessions from three continents have
been studied (a) using 38 nuclear SSR (nuSSRs) markers, (b) using five chloroplast SSR (cpSSR) markers yielding 5 polymorphic
loci and (c) by detecting the differences in a 468 bp fragment from the non-coding region of chloroplast DNA. A clear separation
was found between Eritrean/Ethiopian barley and barley from West Asia and North Africa (WANA) as well as from Europe. The
data from chloroplast DNA clearly indicate that the wild barley (H. vulgare ssp. spontaneum) as it is found today in the “Fertile Crescent” might not be the progenitor of the barley cultivated in Eritrea (and Ethiopia).
Consequently, an independent domestication might have taken place at the Horn of Africa.
Jihad Orabi and Gunter Backes have contributed equally to this work. 相似文献
74.
Background
In proteomics experiments, database-search programs are the method of choice for protein identification from tandem mass spectra. As amino acid sequence databases grow however, computing resources required for these programs have become prohibitive, particularly in searches for modified proteins. Recently, methods to limit the number of spectra to be searched based on spectral quality have been proposed by different research groups, but rankings of spectral quality have thus far been based on arbitrary cut-off values. In this work, we develop a more readily interpretable spectral quality statistic by providing probability values for the likelihood that spectra will be identifiable. 相似文献75.
S. Kicherer G. Backes U. Walther A. Jahoor 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2000,100(6):881-888
The Hordeum vulgare accession ’HOR 1063’ was crossed with the barley cultivar Krona, and 220 doubled haploid lines were produced based on this
cross. A molecular map was constructed based on RFLP markers. Field trials were performed over 2 years and at two locations.
In field trials, resistance to leaf rust by means of artificial infection, heading date, plant height and Kernel weight were
assessed. For leaf rust resistance, 4 QTLs were localised, that explained 96.1% of the genetic variation. One QTL on chromosome
4H confirmed a position found in another genetic background and one mapped to the same position as Rph16 on chromosome 2H. All digenic effects decreased the effects of the respective QTLs. In addition to the denso-locus and the hex-v locus, other QTLs influencing heading date, plant length and kernel weight were found in this cross.
Received: 16 July 1999 / Accepted: 7 September 1999 相似文献
76.
Relationship between the rate of reductase-cytochrome P450 complex formation and the rate of first electron transfer. 总被引:1,自引:0,他引:1
Substrate has recently been shown to affect (a) the high spin content of cytochrome P450 (b) the rate of first electron transfer when LM2 (P450 2B4) and reductase were in a preformed complex, and (c) the rate of functional complex formation between NADPH-cytochrome P450 reductase and cytochrome P450 LM2. When comparing the effect of substrate on each of these parameters, the strongest correlation was demonstrated between the rate of first electron transfer through the preformed complex and the rate of functional complex formation (W.L. Backes and C.S. Eyer, 1989, J. Biol. Chem. 264, 6252-6259). The relationship among high spin content, reduction rate, and the rate of functional complex formation was examined using a number of different cytochrome P450 isozymes. The goal of this study was to determine if the previously established relationship between reduction rate and the rate of reductase-P450 complex formation was a feature only of LM2, or a general characteristic of the cytochrome P450 system. Substrate addition caused an increase in first electron transfer for each of the isozymes examined, with high spin content being increased with cytochromes P450 2B1 (PBRLM5) and P450 2B2 (PBRLM6). Substrate addition to cytochrome P450 2C6 (PBRLM4) resulted in a small decrease in high spin content. P450 2B1 and P450 2B2 showed a positive correlation between substrate-mediated stimulation of reduction and high spin content, whereas P450 2C6 showed a negative correlation between these variables. Substrate also increased the rate of reductase-P450 association for each of the isozymes examined. When compared to the degree of stimulation of reduction through a preformed complex, a strong positive correlation was obtained with each isozyme examined. These results demonstrate that the increase in both the rate of functional reductase-P450 complex formation and the rate of first electron transfer is not simply a property of LM2, but appears to be a general characteristic of many cytochrome P450 isozymes. 相似文献
77.
The class of 2‐isopropyl‐5‐methylbicyclo[4.1.0]heptane‐7‐carboxamides, 1 – 4 , has been identified as potent umami‐tasting molecules. A scalable synthesis of this challenging scaffold and new sensory insights will be presented. Interestingly, the umami characteristics differ remarkably, depending on constitutional and stereochemical features of the parent scaffold. During our studies, we could identify the carboxamide moiety as a crucial factor to influence the umami intensity of these scaffolds. In addition, the configuration of the cyclopropyl moiety exerts some influence, whereas the absolute configuration of the menthyl scaffold, at least the tested D ‐ and L ‐configuration, is less important. 相似文献
78.
Rajarshi Ghosh Likun Wang Eric S. Wang B. Gayani K. Perera Aeid Igbaria Shuhei Morita Kris Prado Maike Thamsen Deborah Caswell Hector Macias Kurt F. Weiberth Micah J. Gliedt Marcel V. Alavi Sanjay B. Hari Arinjay K. Mitra Barun Bhhatarai Stephan C. Schürer Erik L. Snapp Douglas B. Gould Michael S. German Bradley J. Backes Dustin J. Maly Scott A. Oakes Feroz R. Papa 《Cell》2014
79.
René M. H. Besseling Jacobus F. A. Jansen Geke M. Overvliet Sylvie J. M. van der Kruijs Saskia C. M. Ebus Anton de Louw Paul A. M. Hofman Johannes S. H. Vles Albert P. Aldenkamp Walter H. Backes 《PloS one》2013,8(12)
Introduction
Rolandic epilepsy (RE) is a childhood epilepsy with centrotemporal (rolandic) spikes, that is increasingly associated with language impairment. In this study, we tested for a white matter (connectivity) correlate, employing diffusion weighted MRI and language testing.Methods
Twenty-three children with RE and 23 matched controls (age: 8–14 years) underwent structural (T1-weighted) and diffusion-weighted MRI (b = 1200 s/mm2, 66 gradient directions) at 3T, as well as neuropsychological language testing. Combining tractography and a cortical segmentation derived from the T1-scan, the rolandic tract were reconstructed (pre- and postcentral gyri), and tract fractional anisotropy (FA) values were compared between patients and controls. Aberrant tracts were tested for correlations with language performance.Results
Several reductions of tract FA were found in patients compared to controls, mostly in the left hemisphere; the most significant effects involved the left inferior frontal (p = 0.005) and supramarginal (p = 0.004) gyrus. In the patient group, lower tract FA values were correlated with lower language performance, among others for the connection between the left postcentral and inferior frontal gyrus (p = 0.043, R = 0.43).Conclusion
In RE, structural connectivity is reduced for several connections involving the rolandic regions, from which the epileptiform activity originates. Most of these aberrant tracts involve the left (typically language mediating) hemisphere, notably the pars opercularis of the inferior frontal gyrus (Broca’s area) and the supramarginal gyrus (Wernicke’s area). For the former, reduced language performance for lower tract FA was found in the patients. These findings provide a first microstructural white matter correlate for language impairment in RE. 相似文献80.