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991.
Direct NMR observation and DFT calculations of a hydrogen bond at the active site of a 44 kDa enzyme
Eletsky A Heinz T Moreira O Kienhöfer A Hilvert D Pervushi K 《Journal of biomolecular NMR》2002,24(1):31-39
A hydrogen bond between the amide backbone of Arg7 and the remote imidazole side chain of His106 has been directly observed by improved TROSY-NMR techniques in the 44 kDa trimeric enzyme chorismate mutase from Bacillus subtilis. The presence of this hydrogen bond in the free enzyme and its complexes with a transition state analog and the reaction product was demonstrated by measurement of 15N-15N and 1H-15N trans-hydrogen bond scalar couplings, 2h
J
NN and 1h
J
HN, and by transfer of nuclear polarization across the hydrogen bond. The conformational dependences of these coupling constants were analyzed using sum-over-states density functional perturbation theory (SOS-DFPT). The observed hydrogen bond might stabilize the scaffold at the active site of BsCM. Because the Arg7-His106 hydrogen bond has not been observed in any of the high resolution crystal structures of BsCM, the measured coupling constants provide unique information about the enzyme and its complexes that should prove useful for structural refinement of atomic models. 相似文献
992.
Nolte O Rickert A Ehrhard I Ledig S Sonntag HG 《FEMS immunology and medical microbiology》2002,32(2):91-95
For the purpose of establishing a model to study host-bacteria interaction and virulence mechanisms of Neisseria meningitidis during the septic phase of disease a modified human whole blood model of infection is proposed. Compared to published whole blood models the current model was modified with respect to the initial number of viable bacteria (10(4) cfu ml(-1)), the anticoagulant used and the incubation time. The results obtained after incubation of a number of human blood samples from healthy volunteers for 24 h with serogroup B meningococci were in good agreement with findings reported from patients who suffered severe meningococcal disease. 相似文献
993.
Kulhavý D Cegan A Komers K Mindl J 《Zeitschrift für Naturforschung. C, Journal of biosciences》2002,57(5-6):496-499
The activity of every substance I inhibiting an enzymatic reaction can be approximately evaluated by the index PI50. This paper describes a simple and fast method of estimate and/ or determination of this index. The method is based on the linearity of the dependence of the ratio of reaction rates of uninhibited and inhibited reaction vs. concentration of the inhibitor at constant initial substrate and enzyme concentrations for fully competitive, noncompetitive, uncompetitive and mixed type of inhibition by the one inhibitor. The validity of the method is demonstrated by four inhibitors of hydrolysis of acetylthiocholine by butyrylcholine esterase. 相似文献
994.
995.
Loss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti 总被引:15,自引:0,他引:15
Although large human populations have been safely immunized against tuberculosis with two live vaccines, Mycobacterium bovis BCG or Mycobacterium microti, the vole bacillus, the molecular basis for the avirulence of these vaccine strains remains unknown. Comparative genomics has identified a series of chromosomal deletions common to both virulent and avirulent species but only a single locus, RD1, that has been deleted from M. bovis BCG and M. microti. Restoration of RD1, by gene knock-in, resulted in a marked change in colonial morphology towards that of virulent tubercle bacilli. Three RD1-encoded proteins were localized in the cell wall, and two of them, the immunodominant T-cell antigens ESAT-6 and CFP-10, were also found in culture supernatants. The BCG::RD1 and M. microti::RD1 knock-ins grew more vigorously than controls in immunodeficient mice, inducing extensive splenomegaly and granuloma formation. Increased persistence and partial reversal of attenuation were observed when immunocompetent mice were infected with the BCG::RD1 knock-in, whereas BCG controls were cleared. Knocking-in five other RD loci did not affect the virulence of BCG. This study describes a genetic lesion that contributes to safety and opens new avenues for vaccine development. 相似文献
996.
Pilloff RK Devadas SK Enyedi A Raina R 《The Plant journal : for cell and molecular biology》2002,30(1):61-70
We describe the characterization of a novel gain-of-function Arabidopsis mutant, dll1 (disease-like lesions1), which spontaneously develops lesions mimicking bacterial speck disease and constitutively expresses biochemical and molecular markers associated with pathogen infection. Despite the constitutive expression of defense-related responses, dll1 is unable to suppress the growth of virulent pathogens. However, dll1 elicits normal hypersensitive response in response to avirulent pathogens, thus indicating that dll1 is not defective in the induction of normal resistance responses. The lesion+ leaves of dll1 support the growth of hrcC mutant of Pseudomonas syringae, which is defective in the transfer of virulence factors into the plant cells, and therefore non-pathogenic to wild-type Col-0 plants. This suggests that dll1 intrinsically expresses many of the cellular processes that are required for pathogen growth during disease. Epistasis analyses reveal that salicylic acid and NPR1 are required for lesion formation, while ethylene modulates lesion development in dll1, suggesting that significant overlap exist between the signalling pathways leading to resistance- and disease-associated cell death. Our results suggest that host cell death during compatible interactions, at least in part, is genetically controlled by the plant and DLL1 may positively regulate this process. 相似文献
997.
Alexander RP Warrellow GJ Eaton MA Boyd EC Head JC Porter JR Brown JA Reuberson JT Hutchinson B Turner P Boyce B Barnes D Mason B Cannell A Taylor RJ Zomaya A Millican A Leonard J Morphy R Wales M Perry M Allen RA Gozzard N Hughes B Higgs G 《Bioorganic & medicinal chemistry letters》2002,12(11):1451-1456
The discovery, synthesis and biological activity of a series of triarylethane phosphodiesterase 4 inhibitors is described. Structure-activity relationship studies are presented for CDP840 (29), a potent, chiral, selective inhibitor of PDE 4 (IC(50) 4nM). CDP840 is non-emetic in the ferret at 30mgkg(-1) (po), active in models of inflammation and reverses ozone-induced bronchial hyperreactivity in the guinea pig. 相似文献
998.
The ubiquitin system recognizes degradation signals of protein substrates through E3-E2 ubiquitin ligases, which produce a substrate-linked multi-ubiquitin chain. Ubiquitinated substrates are degraded by the 26S proteasome, which consists of the 20S protease and two 19S particles. We previously showed that UBR1 and UFD4, two E3 ligases of the yeast Saccharomyces cerevisiae, interact with specific proteasomal subunits. Here we advance this analysis for UFD4 and show that it interacts with RPT4 and RPT6, two subunits of the 19S particle. The 201-residue amino-terminal region of UFD4 is essential for its binding to RPT4 and RPT6. UFD4(DeltaN), which lacks this N-terminal region, adds ubiquitin to test substrates with apparently wild-type activity, but is impaired in conferring short half-lives on these substrates. We propose that interaction of a targeted substrate with the 26S proteasome involves contacts of specific proteasomal subunits with the substrate-bound ubiquitin ligase, with the substrate-linked multi-ubiquitin chain and with the substrate itself. This multiple-site binding may function to slow down dissociation of the substrate from the proteasome and to facilitate the unfolding of substrate through ATP-dependent movements of the chaperone subunits of the 19S particle. 相似文献
999.
Mulder NJ Apweiler R Attwood TK Bairoch A Bateman A Binns D Biswas M Bradley P Bork P Bucher P Copley R Courcelle E Durbin R Falquet L Fleischmann W Gouzy J Griffith-Jones S Haft D Hermjakob H Hulo N Kahn D Kanapin A Krestyaninova M Lopez R Letunic I Orchard S Pagni M Peyruc D Ponting CP Servant F Sigrist CJ;InterPro Consortium 《Briefings in bioinformatics》2002,3(3):225-235
1000.