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991.
992.
Upregulation of mitochondrial peripheral benzodiazepine receptor expression by cytokine-induced damage of human pancreatic islets 总被引:2,自引:0,他引:2
993.
Evolution of the phosphoglycerate mutase processed gene in human and chimpanzee revealing the origin of a new primate gene 总被引:3,自引:0,他引:3
Processed genes are created by retroposition from messenger RNA of expressed genes. The estimated amount of processed copies of genes in the human genome is 10,000-14,000. Some of these might be pseudogenes with the expected pattern for nonfunctional sequences, but some others might be an important source of new genes. We have studied the evolution of a Phosphoglycerate mutase processed gene (PGAM3) described in humans and believed to be a pseudogene. We sequenced PGAM3 in chimpanzee and macaque and obtained polymorphism data for human coding region. We found evidence that PGAM3 likely produces a functional protein, as an example of addressing functionality for human processed pseudogenes. First, the open reading frame was intact despite many deletions that occurred in the 3' untranslated region. Second, it appears that the gene is expressed. Finally, interspecies and intraspecies variation for PGAM3 was not consistent with the neutral model proposed for pseudogenes, suggesting that a new functional primate gene has originated. Amino acid divergence was significantly higher than synonymous divergence in PGAM3 lineage, supporting positive selection acting in this gene. This role of selection was further supported by the excess of rare alleles in a population genetic analysis. PGAM3 is located in a region of very low recombination; therefore, it is conceivable that the rapid fixation events in this newly arising gene may have contributed to a selective sweep of variation in the region. 相似文献
994.
Pathogenic bacteria are specifically adapted to bind to their customary host. Disease is then caused by subsequent colonization and/or invasion of the local environmental niche. Initial binding of Haemophilus influenzae type b to the human nasopharynx is facilitated by Hib pili, filaments expressed on the bacterial surface. With three-dimensional reconstruction of electron micrograph images, we show that Hib pili comprise a helix 70 A in diameter with threefold symmetry. The Hib pilus filament has 3.0 subunits per turn, with each set of three subunits translated 26.9 A along and rotated 53 degrees about the helical axis. Amino acid sequence analysis of pilins from Hib pili and from P-pili expressed on uropathogenic Escherichia coli were used to predict the physical location of the highly variable and immunogenic region of the HifA pilin in the Hib pilus structure. Structural differences between Hib pili and P-pili suggest a difference in the strategies by which bacteria remain bound to their host cells: P-pili were shown to be capable of unwinding to five times their original length (E. Bullitt and L. Makowski, Nature 373:164-167, 1995), while damage to Hib pili occurs by slight shearing of subunits with respect to those further along the helical axis. This capacity to resist unwinding may be important for continued adherence of H. influenzae type b to the nasopharynx, where the three-stranded Hib pilus filaments provide a robust tether to withstand coughs and sneezes. 相似文献
995.
Direct interaction between mammalian DNA polymerase beta and proliferating cell nuclear antigen 总被引:6,自引:0,他引:6
Kedar PS Kim SJ Robertson A Hou E Prasad R Horton JK Wilson SH 《The Journal of biological chemistry》2002,277(34):31115-31123
Proliferating cell nuclear antigen (PCNA) plays an essential role in nucleic acid metabolism as a component of the DNA replication and DNA repair machinery. As such, PCNA interacts with many proteins that have a sequence motif termed the PCNA interacting motif (PIM) and also with proteins lacking a PIM. Three regions in human and rat DNA polymerases beta (beta-pol) that resemble the consensus PIM were identified, and we show here that beta-polymerase and PCNA can form a complex both in vitro and in vivo. Immunoprecipitation experiments, yeast two-hybrid analysis, and overlay binding assays were used to examine the interaction between the two proteins. Competition experiments with synthetic PIM-containing peptides suggested the importance of a PIM in the interaction, and studies of a beta-polymerase PIM mutant, H222A/F223A, demonstrated that this alteration blocked the interaction with PCNA. The results indicate that at least one of the PIM-like sequences in beta-polymerase appears to be a functional PIM and was required in the interaction between beta-polymerase and PCNA. 相似文献
996.
Feliu JX Ferrer-Miralles N Blanco E Cazorla D Sobrino F Villaverde A 《Biochimica et biophysica acta》2002,1596(2):212-224
Peptide display on solvent-exposed surfaces of engineered enzymes allows them to respond to anti-peptide antibodies by detectable changes in their enzymatic activity, offering a new principle for biosensor development. In this work, we show that multiple peptide insertion in the vicinity of the Escherichia coli beta-galactosidase active site dramatically increases the enzyme responsiveness to specific anti-peptide antibodies. The modified enzymes HD7872A and HT7278CA, carrying eight and 12 copies respectively of a foot-and-mouth disease peptide per enzyme molecule, show antibody-mediated activation factors higher than those previously observed in the first generation enzymatic sensors, for HT7278CA being close to 400%. The analysis of the signal transduction process with multiple inserted proteins strongly suggests a new, non-exclusive mechanism of enzymatic regulation in which the target proteins might be stabilised by the bound antibody, extending the enzyme half-life and consequently enhancing the signal-background ratio. In addition, the tested sensors are differently responsive to sera from immune farm animals, depending on the antigenic similarity between the B-cell epitopes in the immunising virus and those in the peptide used as sensing element on the enzyme surface. Altogether, these results point out the utility of these enzymatic biosensors for a simple diagnosis of foot-and-mouth disease in an extremely fast homogeneous assay. 相似文献
997.
Protein kinase CK2: Signaling and tumorigenesis in the mammary gland 总被引:11,自引:0,他引:11
998.
999.
Esther K. Schmitt D. Hoepfner P. Krastel 《Journal of industrial microbiology & biotechnology》2016,43(2-3):249-260
From the start of the pharmaceutical research natural products played a key role in drug discovery and development. Over time many discoveries of fundamental new biology were triggered by the unique biological activity of natural products. Unprecedented chemical structures, novel chemotypes, often pave the way to investigate new biology and to explore new pathways and targets. This review summarizes the recent results in the area with a focus on research done in the laboratories of Novartis Institutes for BioMedical Research. We aim to put the technological advances in target identification techniques in the context to the current revival of phenotypic screening and the increasingly complex biological questions related to drug discovery. 相似文献
1000.
Fred R. Wolf Esther K. Nemethy Jonathan H. Blanding James A. Bassham 《Phytochemistry》1985,24(4):733-737
A ‘resting state’ isolate of the hydrocarbon-producing alga Botryococcus braunii photoassimilated sodium [14C]bicarbonate at rates comparable to fast growing algae, such as Chlorella (> 1.50 μg atoms 14C/mg chlorophyll·hr). Early in the reaction (up to several min), most of the radioactivity was associated with water-soluble metabolites. However, labelling of hexane-soluble compounds steadily from ca 3% at 15 sec to over 50% of the total incorporated 14C at 60 min. The purified hexane fraction, which consisted of a series of botryococcenes and squalene, constituted a relatively constant proportion (40–45%) of the total hexane-soluble radioactivity at all but the earliest time points (< 60 sec). This fraction initially consisted almost exclusively of a C30 botryococcene (ca 91%) and squalene (ca 8%); however, small amounts of radioactivity sequentially appeared in the C31, C32 and C34 botryococcenes. The results of pulse-chase experiments implicated the C30 botryococcene as the precursor of the higher homologues; during the chase, loss of radioactivity from the C30 compound was accompanied by a concomitant increase in the labelling of the C31 and C32 compounds. This study provides further evidence that the relatively slow growth of Botryococcus in culture may result, in part, from the diversion of a large proportion of reduced carbon into energetically expensive compounds and that the slower growth rate in the ‘resting state’ cannot be totally attributed to an impaired or intrinsically slow metabolism. 相似文献