排序方式: 共有99条查询结果,搜索用时 15 毫秒
91.
Compaan DM Gonzalez LC Tom I Loyet KM Eaton D Hymowitz SG 《The Journal of biological chemistry》2005,280(47):39553-39561
Five CD28-like proteins exert positive or negative effects on immune cells. Only four of these five receptors interact with members of the B7 family. The exception is BTLA (B and T lymphocyte attenuator), which instead interacts with the tumor necrosis factor receptor superfamily member HVEM (herpes virus entry mediator). To better understand this interaction, we determined the 2.8-A crystal structure of the BTLA-HVEM complex. This structure shows that BTLA binds the N-terminal cysteine-rich domain of HVEM and employs a unique binding surface compared with other CD28-like receptors. Moreover, the structure shows that BTLA recognizes the same surface on HVEM as gD (herpes virus glycoprotein D) and utilizes a similar binding motif. Light scattering analysis demonstrates that the extracellular domain of BTLA is monomeric and that BTLA and HVEM form a 1:1 complex. Alanine-scanning mutagenesis of HVEM was used to further define critical binding residues. Finally, BTLA adopts an immunoglobulin I-set fold. Despite structural similarities to other CD28-like members, BTLA represents a unique co-receptor. 相似文献
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McPherson DB Kilker RP Foley TD 《Biochemical and biophysical research communications》2002,296(2):413-418
Nitric oxide (*NO) can act as an antioxidant by directly scavenging reactive free radicals, inhibiting the oxidative chemistry of iron, and signaling the up-regulation of antioxidant enzymes. However, the cellular utility of *NO as an antioxidant requires that constitutive nitric oxide synthase (NOS) be activated rapidly by a signal(s) for oxidant formation. We report here that superoxide (O2*-), added directly as potassium superoxide (KO2), produced a superoxide dismutase-sensitive and hydrogen peroxide-independent stimulation of NOS activity, measured by the conversion of [3H]arginine to [3H]citrulline and nitrite formation, in a synaptic particulate fraction from rat brain cerebral cortex. O2*- produced maximal activation of NOS in the presence of the antioxidant urate and ATP. Stimulation of NOS activity by O2*- was abolished by N-monomethyl-L-arginine and by the Ca2+ chelator EGTA but not by 7-nitroindazole, which would be expected to inhibit neuronal NOS. We propose that limited activation of NOS by O2*- may be an important contributor to brain oxidant defenses and, more generally, a signal for cellular adaptation and survival, although excessive generation of nitrogen oxides would be expected to produce neurotoxicity. 相似文献
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The crystal structure of a proliferation-inducing ligand, APRIL 总被引:9,自引:0,他引:9
Wallweber HJ Compaan DM Starovasnik MA Hymowitz SG 《Journal of molecular biology》2004,343(2):283-290
A proliferation-inducing ligand (APRIL) is a TNF-like cytokine that stimulates tumor cell growth. Within the TNF ligand superfamily, APRIL is most similar to B-cell activation factor (BAFF) with which it shares 30% sequence identity. APRIL binds the receptors B-cell maturation antigen (BCMA) and TACI with high affinity; both of these receptors have also been shown to bind BAFF, although BCMA has significantly higher affinity for APRIL than BAFF. Determination of the crystal structure of APRIL from three crystallization conditions at resolutions of 1.8-2.4A over a pH range from 5.0 to 8.5 reveals a compact trimeric ligand with a backbone fold very similar to that of BAFF (1.1A RMSD over 122 structurally equivalent Calpha atoms), with the exception of differences in the AA' and DE loop regions. Whereas BAFF has been shown to form 20-trimer assemblies under certain conditions, the molecular determinants required for BAFF-like assemblies are absent in the APRIL structure. No crystal packing suggestive of the formation of higher-order assemblies is seen in any of the crystal forms nor does the structure vary significantly between pH 5.0 and 8.5. Modeling of the APRIL-BCMA complex shows the resulting interface is in agreement with mutagenesis data. 相似文献
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Deanne W. Sammond John M. Yarbrough Elisabeth Mansfield Yannick J. Bomble Sarah E. Hobdey Stephen R. Decker Larry E. Taylor Michael G. Resch Joseph J. Bozell Michael E. Himmel Todd B. Vinzant Michael F. Crowley 《The Journal of biological chemistry》2014,289(30):20960-20969
The inhibitory action of lignin on cellulase cocktails is a major challenge to the biological saccharification of plant cell wall polysaccharides. Although the mechanism remains unclear, hydrophobic interactions between enzymes and lignin are hypothesized to drive adsorption. Here we evaluate the role of hydrophobic interactions in enzyme-lignin binding. The hydrophobicity of the enzyme surface was quantified using an estimation of the clustering of nonpolar atoms, identifying potential interaction sites. The adsorption of enzymes to lignin surfaces, measured using the quartz crystal microbalance, correlates to the hydrophobic cluster scores. Further, these results suggest a minimum hydrophobic cluster size for a protein to preferentially adsorb to lignin. The impact of electrostatic contribution was ruled out by comparing the isoelectric point (pI) values to the adsorption of proteins to lignin surfaces. These results demonstrate the ability to predict enzyme-lignin adsorption and could potentially be used to design improved cellulase cocktails, thus lowering the overall cost of biofuel production. 相似文献
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Dai-Shi Su John J. Lim Elizabeth Tinney Thomas J. Tucker Sandeep Saggar John T. Sisko Bang-Lin Wan Mary Beth Young Kenneth D. Anderson Deanne Rudd Vandna Munshi Carolyn Bahnck Peter J. Felock Meiquing Lu Ming-Tain Lai Sinoeun Touch Gregory Moyer Daniel J. DiStefano Jessica A. Flynn Yuexia Liang Neville J. Anthony 《Bioorganic & medicinal chemistry letters》2010,20(15):4328-4332
Biaryl ethers were recently reported as potent NNRTIs. Herein, we disclose a detailed effort to modify the previously reported compound 1. We have designed and synthesized a series of novel pyrazole derivatives as a surrogate for pyrazolopyridine motif that were potent inhibitors of HIV-1 RT with nanomolar intrinsic activity on the WT and key mutant enzymes and potent antiviral activity in infected cells. 相似文献
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