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排序方式: 共有884条查询结果,搜索用时 15 毫秒
71.
Stauffer SR Stanton MG Gregro AR Steinbeiser MA Shaffer JR Nantermet PG Barrow JC Rittle KE Collusi D Espeseth AS Lai MT Pietrak BL Holloway MK McGaughey GB Munshi SK Hochman JH Simon AJ Selnick HG Graham SL Vacca JP 《Bioorganic & medicinal chemistry letters》2007,17(6):1788-1792
A series of low-molecular weight 2,6-diamino-isonicotinamide BACE-1 inhibitors containing an amine transition-state isostere were synthesized and shown to be highly potent in both enzymatic and cell-based assays. These inhibitors contain a trans-S,S-methyl cyclopropane P(3) which bind BACE-1 in a 10s-loop down conformation giving rise to highly potent compounds with favorable molecular weight and moderate to high susceptibility to P-glycoprotein (P-gp) efflux. 相似文献
72.
SOCS-1 is a central mediator of steroid-increased thymocyte apoptosis and decreased survival following sepsis 总被引:1,自引:0,他引:1
Chung CS Chen Y Grutkoski PS Doughty L Ayala A 《Apoptosis : an international journal on programmed cell death》2007,12(7):1143-1153
Suppressor of Cytokine Signaling (SOCS) proteins are recently identified inhibitors/regulators of cytokine/growth factor signaling
pathways. We have previously shown that SOCS-3 is upregulated in mice after sepsis induced by cecal ligation and puncture;
however, the contribution of SOCS-1 to septic morbidity and mortality is unclear. In the present study, we characterized SOCS-1
expression in different tissues and delineated putative mechanisms effecting SOCS-1 expression in thymus from septic mice.
We observed no difference in SOCS-1 expression in blood, peritoneal leukocytes, lung, and spleen taken from sham or septic
animals at 24 h after surgery. In contrast, SOCS-1 expression in thymus declined significantly after sepsis and this down-regulation
of SOCS-1 was associated with increased thymocyte apoptosis as well as augmented Bax recruitment to the mitochondria. Administration
of RU-38486, a steroid receptor antagonist, reversed the above effects in the septic thymus. Furthermore, SOCS-1+/− mice showed
a significant higher mortality when compared to SOCS-1+/+ mice after sepsis. Together, these results show that sepsis increases
steroid-induced thymic lymphoid cell apoptosis, which is associated with reduced SOCS-1 expression and increased Bax translocation
to mitochondria. Survival data suggests that SOCS-1 protein may play an important role in sepsis. 相似文献
73.
Structural and functional analyses of methyl-lysine binding by the malignant brain tumour repeat protein Sex comb on midleg 总被引:2,自引:0,他引:2 下载免费PDF全文
Grimm C de Ayala Alonso AG Rybin V Steuerwald U Ly-Hartig N Fischle W Müller J Müller CW 《EMBO reports》2007,8(11):1031-1037
Sex comb on midleg (Scm) is a member of the Polycomb group of proteins involved in the maintenance of repression of Hox and other developmental control genes in Drosophila. The two malignant brain tumour (MBT) repeats of Scm form a domain that preferentially binds to monomethylated lysine residues either as a free amino acid or in the context of peptides, while unmodified or di- or trimethylated lysine residues are bound with significantly lower affinity. The crystal structure of a monomethyl-lysine-containing histone tail peptide bound to the MBT repeat domain shows that the methyl-lysine side chain occupies a binding pocket in the second MBT repeat formed by three conserved aromatic residues and one aspartate. Insertion of the monomethylated side chain into this pocket seems to be the main contributor to the binding affinity. Functional analyses in Drosophila show that the MBT domain of Scm and its methyl-lysine-binding activity are required for repression of Hox genes. 相似文献
74.
Elsa Pimienta Julio C Ayala Caridad Rodríguez Astrid Ramos Lieve Van Mellaert Carlos Vallín Jozef Anné 《Microbial cell factories》2007,6(1):20
Background
Streptokinase (SK) is a potent plasminogen activator with widespread clinical use as a thrombolytic agent. It is naturally secreted by several strains of beta-haemolytic streptococci. The low yields obtained in SK production, lack of developed gene transfer methodology and the pathogenesis of its natural host have been the principal reasons to search for a recombinant source for this important therapeutic protein. We report here the expression and secretion of SK by the Gram-positive bacterium Streptomyces lividans. The structural gene encoding SK was fused to the Streptomyces venezuelae CBS762.70 subtilisin inhibitor (vsi) signal sequence or to the Streptomyces lividans xylanase C (xlnC) signal sequence. The native Vsi protein is translocated via the Sec pathway while the native XlnC protein uses the twin-arginine translocation (Tat) pathway. 相似文献75.
Alesci Marco Smith Rebecca L. Ayala Santacruz Jorge Damian Camperio Ciani Andrea 《Primates; journal of primatology》2022,63(2):161-171
Primates - Increasing urbanisation is encroaching into natural habitats and sometimes forcing wildlife into urban centres. Whether or not wildlife can thrive in an urban environment is dependent on... 相似文献
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78.
Marcela Ayala Cesar V. Batista Rafael Vazquez-Duhalt 《Journal of biological inorganic chemistry》2011,16(1):63-68
Heme peroxidases are subject to a mechanism-based oxidative inactivation. During the catalytic cycle, the heme group is activated
to form highly oxidizing species, which may extract electrons from the protein itself. In this work, we analyze changes in
residues prone to oxidation owing to their low redox potential during the peroxide-mediated inactivation of chloroperoxidase
from Caldariomyces fumago under peroxidasic catalytic conditions. Surprisingly, we found only minor changes in the amino acid content of the fully
inactivated enzyme. Our results show that tyrosine residues are not oxidized, whereas all tryptophan residues are partially
oxidized in the inactive protein. The data suggest that the main process leading to enzyme inactivation is heme destruction.
The molecular characterization of the peroxide-mediated inactivation process could provide specific targets for the protein
engineering of this versatile peroxidase. 相似文献
79.
80.
Lateral gene transfer (LGT) is a major evolutionary mechanism in prokaryotes. Knowledge about LGT--particularly, multicellular--eukaryotes has only recently started to accumulate. A widespread assumption sees the gene as the unit of LGT, largely because little is yet known about how LGT chances are affected by structural/functional features at the subgenic level. Here we trace the evolutionary trajectory of VEin Patterning 1, a novel gene family known to be essential for plant development and defense. At the subgenic level VEP1 encodes a dinucleotide-binding Rossmann-fold domain, in common with members of the short-chain dehydrogenase/reductase (SDR) protein family. We found: i) VEP1 likely originated in an aerobic, mesophilic and chemoorganotrophic α-proteobacterium, and was laterally propagated through nets of ecological interactions, including multiple LGTs between phylogenetically distant green plant/fungi-associated bacteria, and five independent LGTs to eukaryotes. Of these latest five transfers, three are ancient LGTs, implicating an ancestral fungus, the last common ancestor of land plants and an ancestral trebouxiophyte green alga, and two are recent LGTs to modern embryophytes. ii) VEP1's rampant LGT behavior was enabled by the robustness and broad utility of the dinucleotide-binding Rossmann-fold, which provided a platform for the evolution of two unprecedented departures from the canonical SDR catalytic triad. iii) The fate of VEP1 in eukaryotes has been different in different lineages, being ubiquitous and highly conserved in land plants, whereas fungi underwent multiple losses. And iv) VEP1-harboring bacteria include non-phytopathogenic and phytopathogenic symbionts which are non-randomly distributed with respect to the type of harbored VEP1 gene. Our findings suggest that VEP1 may have been instrumental for the evolutionary transition of green plants to land, and point to a LGT-mediated 'Trojan Horse' mechanism for the evolution of bacterial pathogenesis against plants. VEP1 may serve as tool for revealing microbial interactions in plant/fungi-associated environments. 相似文献