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51.
Crystal structure of TNF-alpha mutant R31D with greater affinity for receptor R1 compared with R2 总被引:2,自引:0,他引:2
Reed C; Fu ZQ; Wu J; Xue YN; Harrison RW; Chen MJ; Weber IT 《Protein engineering, design & selection : PEDS》1997,10(10):1101-1107
Crystal structures have been determined of recombinant human tumor necrosis
factor-alpha (TNF-alpha) and its R31D mutant that preferentially binds to
TNF receptor R1 with more than seven times the relative affinity of binding
to receptor R2. Crystals of the wild-type TNF were of space group
P4(1)2(1)2 and had unit cell dimensions of a = b = 94.7 and c = 117.4 A.
Refinement of the structure gave an R-factor of 22.3% at 2.5 A resolution.
The crystals of TNF R31D mutant diffracted to 2.3 A resolution, and were of
identical space group to the wild type with unit cell dimensions of a = b =
95.4 and c = 116.2 A, and the structure was refined to an R-factor of
21.8%. The trimer structures of the wild-type and mutant TNF were similar
with a root mean square (r.m.s.) deviation of 0.56 A for Calpha atoms;
however, the subunits within each trimer were more variable with an average
r.m.s. deviation of 1.00 A on Calpha atoms for pairwise comparison of
subunits. Model complexes of TNF with receptors R1 and R2 have been used to
predict TNF-receptor interactions. Arg31 in all three subunits of wild-type
TNF is predicted to form an ionic interaction with the equivalent glutamic
acid in both receptors R1 and R2. Asp31 of the TNF R31D mutant is predicted
to interact differently with the two receptors. The side chain of Asp31 in
two subunits of the TNF mutant is predicted to form hydrogen bond
interactions with Ser59 or Cys70 of R1, while it has no predicted
interactions with R2. The loss of three strong ionic interactions of Arg31
and the electrostatic repulsion of Asp31 with Glu in the receptors is
consistent with the reduced binding of the R31D mutant to both receptors
relative to wild-type TNF. The replacement of these ionic interactions by
two weaker hydrogen bond interactions between Asp31 of the R31D mutant and
R1, compared with no interactions with R2, is in agreement with the
observed preferential binding of the R31D mutant to R1 over R2. Analysis of
the structure and function of receptor-discriminating mutants of TNF will
help understand the biological role of TNF and facilitate its use as an
antitumor agent.
相似文献
52.
A MECHANISTICALLY BASED MATHEMATICAL MODEL OF SULFUR DIOXIDE ABSORPTION INTO A CALCIUM HYDROXIDE SLURRY IN A SPRAY DRYER 总被引:3,自引:0,他引:3
George P. Partridge Wayne T. Davis Robert M. Counce Gregory D. Reed 《Chemical Engineering Communications》1990,96(1):97-112
A mathematical model has been developed to predict So2 absorption and removal during the constant rate drying period of a spray dryer. The model, based on film theory, treats the atomized slurry droplets as spheres containing discrete sorbent particles of slaked lime with the fluid uniformly distributed around the individual particles. The model includes gas and liquid phase mass transfer coefficients as well as resistance to Ca(OH)2 dissolution. A sensitivity analysis has been conducted and a comparison was made between pilot-scale experimental data and model-predicted values of S02 removal efficiency. 相似文献
53.
Field survey of the geometrical isomers of 7,9-dodecadienyl alcohol, acetate, and aldehyde has resulted in attractants and inhibitors for three species of tortricid moths.Epinotia silvertoniensis and an undescribedEpinotia sp. were all attracted to (Z,Z)-7,9-dodecadienyl acetate. AnotherEpinotia sp. was attracted to (Z,Z)-7,9-dodecadienyl acetate and (Z,Z)-7,9-dodecadien-1-ol. Electroantennogram data and inhibition patterns for one of theEpinotia sp. are also reported. In addition,E. criddleana was attracted to lures containing (E)-9-dodecenyl acetate. 相似文献
54.
Reed M. Izatt Steven R. Izatt Don W. Mcbride Jr. Jerald S. Bradshaw James J. Christensen 《Israel journal of chemistry》1985,25(1):27-32
Macrocycle-mediated fluxes of Cd(NO3)2 and of several binary mixtures of Cd(NO3)2 with the nitrate salt of either Na+, K+, Rb+ Cs+, Ag+, Ca2+, Sr2+, Pb2+, Zn2+, or Cu2+ have been determined in a H2O-CHCl3–H2O liquid membrane system. Of the macrocycles studied, 2.2 and 2.2DD most successfully transported Cd2+ In the Cd2+–Mn+ mixtures, Cd2+ was transported selectively with 2.2 when Mn+ was either an alkali or an alkaline earth cation. However, when Mn+ was either Ag+, Pb2+, or Cu2+ the Cd2+ flux was reduced sharply. Generally, cation flux was greater for 2.2DD than for 2.2 with selectivity for Cd2+ being altered also in several cases. Relative fluxes from binary cation mixtures depend on metal cation radius, macrocycle cavity diameter, ligand ring substituent and log K for metal ion-macrocycle interaction. 相似文献
55.
Gudrún V. Skúladóttir Du Shi-Hua Ann E. Brodie Donald J. Reed Rosemary C. Wander 《Lipids》1994,29(5):351-357
Weanling male Sprague-Dawley rats were fed diets for four weeks which differed in their content of n−6 (corn oil; CO) and
n−3 fatty acids (fish oil; FO), but were similar in their content of saturated and monounsaturated fatty acids and vitamin
E. At the end of the four-week feeding period, each dietary group was subdivided into two groups. One group received a single
placebo injection of α-tocopherol-stripped corn oil (TSCO); the other group received a single injection of the free radical
generator, methyl ethyl ketone peroxide (MEKP), in TSCO. Twenty-four hours after injection, the effect of dietary oil and
MEKP treatment on endogenous lipid peroxide (LPO) production (measured as methylene blue formed by the “Determiner LPO” assay),
glutathione (GSH) and vitamin E content, and fatty acid composition of phosphatidylcholine and phosphatidylethanolamine in
heart and liver from unfasted animals were measured. FO-fed rats had significantly heavier hearts and livers, increased levels
of n−3 fatty acids in membrane phospholipids, and higher liver LPO levels than CO-fed rats. MEKP treatment resulted in significantly
lower body weights and liver GSH levels. The data indicate that dietary n−3 fatty acids increase lipid peroxidation in liver
somewhat more than in heart. The study also demonstrates that the effect of induced oxidative stress due to a single dose
of MEKP on lipid peroxide formation and antioxidant status in tissues from unfasted animals was independent of the dietary
oils. 相似文献
56.
The slope of density versus log (pressure) represents the efficiency of compaction forming. A high maximum particle packing density of powders increased the pressing efficiency and the compact density. A high granule density favors a high compact density, whereas, a low granule density favors an increase in the pressing efficiency and the elimination of the intergranular pores; an optimum clearly existed. At a very low forming pressure, the compact density using granules containing a binder was lower; but at a higher forming pressure, the binder acted as a lubricant and assisted particle sliding and rearrangement which increased the pressing efficiency and compact density. 相似文献
57.
Based on the experience of the gasifier users on the efforts and energy for wood chip preparation in a typical gasifier, we have embarked on the development of a gasifier suitable to work with long stick woody biomass as the feed materials. In the context of the impact of gasifiers, as decentralized energy delivery devices such an approach, it is hoped, would be an attractive option in rural areas both in domestic and industrial sectors. In the present paper in the gasifier operation, there is a fixed quantity of char that is combusted to gasify a fixed amount of wood, and the gasifier does not operate in a steady state manner. In this present work, focus is made on the development of a gasifier using long sticks of wood as feed materials. With this concept, a 10 kW thermal output power gasifier is designed and constructed. The gas and airflows can be converted to the air/fuel ratio, the most important aspect of gasifier operation. The air/fuel ratio shows operation in a combustion mode at start up, a gasification mode for the middle part of the run and a charcoal gasification mode at the end of the run. Since the interest here is exploring and validating of this concept, a bottom lit updraft gasifier is designed mainly to look at the gas yield and other favourable factors and to use this gas so obtained for thermal applications. The rate of feed was between 9 and 10 kg/h and continuous operation for 5 h was made in a couple of runs to study the performance. In this paper we report the salient features of our efforts and results, yielding a gasifier efficiency of 73%. 相似文献
58.
The degradation mechanism of a series of polyglycolic/polylactic acid, (PGA/PLA), homo and copolymers synthesized as in Part 11, has been studied vitro. An in vitro test model similar to that described in a previous study9, was used. The effects of time, temperature and pH on the rate and mechanism of degradation were elucidated. The degree of degradation was monitored molecularly by gel permeation chromatography (g.p.c.), tensile strength determination and mass loss measurements. The mechanism of degradation is shown to be by hydrolysis. The copolymers of PGA and PLA are shown to have a wide range of degradation rates governed by the hydrophilic/hydrophobic balance and crystallinity of the respective copolymer. The effect of the glass transition temperature (Tg) of PGA on its sensitivity to degradation is also demonstrated. 相似文献
59.
E. Reed Doke 《Information Systems Management》2013,30(1):37-43
Application development productivity is becoming an increasingly important issue in the MIS department. Unfortunately, dramatic improvements in hardware performance have not been matched with corresponding advances in software development, even though there have been significant investments in productivity tools. This article identifies a range of productivity tools and presents results from a survey of MIS managers that reveals which specific tools are being used and their relative importance to software development productivity. 相似文献
60.
Cell-free apoptosis in Xenopus egg extracts: inhibition by Bcl-2 and requirement for an organelle fraction enriched in mitochondria 总被引:1,自引:0,他引:1
Apoptotic cell death involves a ritual series of morphological changes, presumably reflecting a conserved molecular pathway. We now report that the nuclear events typical of apoptosis can be reproduced in "apoptotic" Xenopus egg extracts. In this cell-free system, nuclear assembly and protein import are initially normal; after 2-4 hr, however, a process of nuclear destruction ensues involving chromatin condensation and the shrinkage and fragmentation of the nuclei. This apoptotic process, which also occurs in nuclei added exogenously, is blocked by the addition of baculovirus-expressed Bcl-2 protein. To block the disintegration of nuclei that are added later, Bcl-2 must be present during this latent period. "Apoptosis" in these extracts requires a dense organelle fraction enriched in mitochondria. The cell-free system described here provides a novel tool for understanding intracellular events in apoptosis and the inhibitory function of Bcl-2. 相似文献