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91.
Aromatic rings act as hydrogen bond acceptors 总被引:24,自引:0,他引:24
Simple energy calculations show that there is a significant interaction between a hydrogen bond donor (like the greater than NH group) and the centre of a benzene ring, which acts as a hydrogen bond acceptor. This interaction, which is about half as strong as a normal hydrogen bond, contributes approximately 3 kcal/mol (1 cal = 4.184 J) of stabilizing enthalpy and is expected to play a significant role in molecular associations. It is of interest that the aromatic hydrogen bond arises from small partial charges centred on the ring carbon and hydrogen atoms: there is no need to consider delocalized electrons. Although some energy calculations have included such partial charges, their role in forming such a strong interaction was not appreciated until after aromatic hydrogen bonds had been observed in protein-drug complexes. 相似文献
92.
D G Levitt 《Biophysical journal》1991,59(2):278-288
The general theory (Levitt, D. G. 1990. Biophys. J. 59:271-277) is applied to a model channel that resembles the acetylcholine receptor channel (ACH). The model incorporates the known features of the ACH geometry and fixed charge locations. The channel has a wide mouth facing the outer solution, tapering to a narrow region facing the interior of the cell. Rings of fixed negative charge are placed at the two surfaces where the bilayer begins, corresponding to the known charges at the ends of the M2 segment. It is assumed that the forces acting on the ion are electrostatic: ion-channel wall, ion-ion, Born image and applied voltage. Analytical expressions for these forces are derived that take account of the low dielectric lipid region. In addition, there is a local hard sphere repulsive force that prevents ions from piling up on each other in regions of the channel with a high fixed charge density. A classical continuum theory is used to obtain an expression for the diffusion coefficient in the channel. The model can mimic the major qualitative and, in many cases, quantitative experimental features of the ACH channel: current-voltage relation, conductance versus concentration and interaction between monovalent and divalent ions. The model calculations were also compared with the site directed mutagenesis experiments of Imoto, K., C. Busch, B. Sakmann, M. Mishina, T. Konno, J. Nakai, H. Bujo, Y. Mori, K. Fukuda, and S. Numa. (1988. Nature (Lond.). 335:645-648) in which the charge at the ends of the channel was systematically varied. 相似文献
93.
Structural diversity in a conserved cholera toxin epitope involved in ganglioside binding.
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M. Shoham T. Scherf J. Anglister M. Levitt E. A. Merritt W. G. Hol 《Protein science : a publication of the Protein Society》1995,4(5):841-848
Cholera is a widespread disease for which there is no efficient vaccine. A better understanding of the conformational rearrangements at the epitope might be very helpful for the development of a good vaccine. Cholera toxin (CT) as well as the closely related heat-labile toxin from Escherichia coli (LT) are composed of two subunits, A and B, which form an oligomeric assembly AB5. Residues 50-64 on the surface of the B subunits comprise a conserved loop (CTP3), which is involved in saccharide binding to the receptor on epithelial cells. This loop exhibits remarkable conformational plasticity induced by environmental constraints. The crystal structure of this loop is compared in the free and receptor-bound toxins as well as in the crystal and solution structures of a complex with TE33, a monoclonal antibody elicited against CTP3. In the toxins this loop forms an irregular structure connecting a beta-strand to the central alpha-helix. Ser 55 and Gln 56 exhibit considerable conformational variability in the five subunits of the unliganded toxins. Saccharide binding induces a change primarily in Ser 55 and Gln 56 to a conformation identical in all five copies. Thus, saccharide binding confers rigidity upon the loop. The conformation of CTP3 in complex with TE33 is quite different. The amino-terminal part of CTP3 forms a beta-turn that fits snugly into a deep binding pocket on TE33, in both the crystal and NMR-derived solution structure. Only 8 and 12 residues out of 15 are seen in the NMR and crystal structures, respectively. Despite these conformational differences, TE33 is cross-reactive with intact CT, albeit with a thousandfold decrease in affinity. This suggests a different interaction of TE33 with intact CT. 相似文献
94.
95.
Conformational transitions of the phosphodiester backbone in native DNA: two-dimensional magic-angle-spinning 31P-NMR of DNA fibers.
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Z Song O N Antzutkin Y K Lee S C Shekar A Rupprecht M H Levitt 《Biophysical journal》1997,73(3):1539-1552
Solid-state 31P-NMR is used to investigate the orientation of the phosphodiester backbone in NaDNA-, LiDNA-, MgDNA-, and NaDNA-netropsin fibers. The results for A- and B-DNA agree with previous interpretations. We verify that the binding of netropsin to NaDNA stabilizes the B form, and find that in NaDNA, most of the phosphate groups adopt a conformation typical of the A form, although there are minor components with phosphate orientations close to the B form. For LiDNA and MgDNA samples, on the other hand, we find phosphate conformations that are in variance with previous models. These samples display x-ray diffraction patterns that correspond to C-DNA. However, we find two distinct phosphate orientations in these samples, one resembling that in B-DNA, and one displaying a twist of the PO4 groups about the O3-P-O4 bisectors. The latter conformation is not in accordance with previous models of C-DNA structure. 相似文献
96.
Simulating the minimum core for hydrophobic collapse in globular proteins. 总被引:2,自引:1,他引:1
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J. Tsai M. Gerstein M. Levitt 《Protein science : a publication of the Protein Society》1997,6(12):2606-2616
To investigate the nature of hydrophobic collapse considered to be the driving force in protein folding, we have simulated aqueous solutions of two model hydrophobic solutes, methane and isobutylene. Using a novel methodology for determining contacts, we can precisely follow hydrophobic aggregation as it proceeds through three stages: dispersed, transition, and collapsed. Theoretical modeling of the cluster formation observed by simulation indicates that this aggregation is cooperative and that the simulations favor the formation of a single cluster midway through the transition stage. This defines a minimum solute hydrophobic core volume. We compare this with protein hydrophobic core volumes determined from solved crystal structures. Our analysis shows that the solute core volume roughly estimates the minimum core size required for independent hydrophobic stabilization of a protein and defines a limiting concentration of nonpolar residues that can cause hydrophobic collapse. These results suggest that the physical forces driving aggregation of hydrophobic molecules in water is indeed responsible for protein folding. 相似文献
97.
Mwayiwawo Madanitsa Linda Kalilani Victor Mwapasa Anna M. van Eijk Carole Khairallah Doreen Ali Cheryl Pace James Smedley Kyaw-Lay Thwai Brandt Levitt Duolao Wang Arthur Kang’ombe Brian Faragher Steve M. Taylor Steve Meshnick Feiko O. ter Kuile 《PLoS medicine》2016,13(9)
BackgroundIn Africa, most plasmodium infections during pregnancy remain asymptomatic, yet are associated with maternal anemia and low birthweight. WHO recommends intermittent preventive therapy in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). However, sulfadoxine-pyrimethamine (SP) efficacy is threatened by high-level parasite resistance. We conducted a trial to evaluate the efficacy and safety of scheduled intermittent screening with malaria rapid diagnostic tests (RDTs) and treatment of RDT-positive women with dihydroartemisinin-piperaquine (DP) as an alternative strategy to IPTp-SP.ConclusionsScheduled screening for malaria parasites with the current generation of RDTs three to four times during pregnancy as part of focused antenatal care was not superior to IPTp-SP in this area with high malaria transmission and high SP resistance and was associated with higher fetal loss and more malaria at delivery.
Trial Registration
Pan African Clinical Trials Registry PACTR201103000280319; ISRCTN Registry ISRCTN69800930 相似文献98.
Joseph E. Levitt 《Expert review of proteomics》2016,13(5):457-469
The acute respiratory distress syndrome (ARDS) is a common cause of acute respiratory failure, and is associated with substantial mortality and morbidity. Dozens of clinical trials targeting ARDS have failed, with no drug specifically targeting lung injury in widespread clinical use. Thus, the need for drug development in ARDS is great. Targeted proteomic studies in ARDS have identified many key pathways in the disease, including inflammation, epithelial injury, endothelial injury or activation, and disordered coagulation and repair. Recent studies reveal the potential for proteomic changes to identify novel subphenotypes of ARDS patients who may be most likely to respond to therapy and could thus be targeted for enrollment in clinical trials. Nontargeted studies of proteomics in ARDS are just beginning and have the potential to identify novel drug targets and key pathways in the disease. Proteomics will play an important role in phenotyping of patients and developing novel therapies for ARDS in the future. 相似文献
99.
A microprecipitation test (MPT) for the detection of adenovirus antibody has been developed. The new procedure combines precipitation of virus particles with specific antibody, separation of unreacted components from the resulting electroneutral virus-antibody complexes by electrophoresis, and detection of these complexes with a protein stain. Type-specific antibody was detected in rabbit antisera but, under similar conditions, antibody in convalescent human sera reacted with adnovirus antigens of types 4 and 7. Paired sera from 57 patients with suspected adenovirus infection were examined for significant rises in antibody activity by the microprecipitation test and by complement fixation. 相似文献
100.
An immunoelectrophoretic procedure utilizing microprecipitation and cellulose acetate electrophoresis was developed for detection of antibody to specific virus. A model system of tobacco mosaic virus and homologous rabbit antiserum is described. 相似文献