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101.
Noe MC Snow SL Wolf-Gouveia LA Mitchell PG Lopresti-Morrow L Reeves LM Yocum SA Liras JL Vaughn M 《Bioorganic & medicinal chemistry letters》2004,14(18):4727-4730
N-Hydroxy-3-hydroxy-4-arylsulfonyltetrahydropyranyl-3-carboxamides were designed as novel inhibitors of MMP-13 and aggrecanase based on known endocyclic hydroxamate inhibitors of matrix metalloproteinases. These compounds offer favorable physicochemical properties and low metabolic clearance. Synthesis and structure-activity relationships are reported. 相似文献
102.
Kinetochores are the specialized protein structures that form on centromeric DNA and direct chromosome segregation. It is critical that all chromosomes assemble a single kinetochore every cell cycle. One hallmark of all eukaryotic kinetochores is CENP-A, an essential centromeric histone H3 (CenH3) variant. Overexpression of CENP-A causes mislocalization to euchromatin, which could lead to deleterious consequences because CENP-A overexpression is associated with colorectal cancer . Although CENP-A protein levels are important for genomic stability, little is known about the mechanisms of CenH3 regulation. Here, we show that the levels of the budding yeast CenH3, Cse4, are regulated by ubiquitin-proteasome-mediated proteolysis. Because mutation of all Cse4 lysine residues did not completely stabilize the protein, we isolated a dominant lethal mutant, CSE4-351, that was stable. The Cse4-351 protein localized to euchromatin, suggesting that proteolysis prevents CenH3 euchromatic localization. When wild-type Cse4 was fused to a degron signal, the soluble Cse4 protein was rapidly degraded, but the centromere bound Cse4 was stable, indicating that centromere localization protects Cse4 from degradation. Taken together, these data identify proteolysis as one mechanism that contributes to the restricted centromere localization of the yeast CenH3. 相似文献
103.
China approves first gene therapy 总被引:6,自引:0,他引:6
104.
Ntshotsho P van Aarde RJ Nicolson SW Jackson TP 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2004,139(4):441-447
Aspects of renal physiology were examined to test the hypothesis that two cryptic species of the genus Mastomys (Mastomys natalensis and Mastomys coucha) are geographically separated by differences in aridity tolerance. Laboratory-bred females of each species were subjected to different levels of salinity in their water source (distilled water, 0.9% NaCl, and 1.5% NaCl; 10 conspecifics in each group) from weaning until sexual maturity. Individuals of the two species exhibited similar rates of water consumption and urine production. The salinity treatments caused sodium diuresis in both species, evident in increased urine volume, decreased osmolality and increased osmotic output. Urine concentration, kidney mass and kidney relative medullary area (RMA) did not differ between species. The results of our study do not support the hypothesis that differences in osmoregulatory ability separate these two cryptic species. Nor do they support the use of salt loading to elicit maximum urine concentrations in mammals. 相似文献
105.
106.
The ability to accurately diagnose the presence of an infective micro-organism is not only important for individual human and animal health and wellbeing, but is also central to surveillance programmes. Effective and sustainable control of many diseases in the developing world depends on the availability of field applicable diagnostics that are cheap, reliable, simple in design and application, and which provide immediate results. This review examines how the genome sequences can be used in the selection of potential candidate proteins for developing new serodiagnostics for African trypanosomiasis. 相似文献
107.
108.
Zollinger SA Suthers RA 《Proceedings. Biological sciences / The Royal Society》2004,271(1538):483-491
The diverse vocal performances of oscine songbirds are produced by the independent but coordinated patterns of activity in muscles controlling separate sound generators on the left and right sides of their duplex vocal organ, the syrinx. Species with different song styles use the two sides of their syrinx in different ways to produce their species-typical songs. Understanding how a vocal mimic copies another species' song may provide an insight into whether there are alternative motor mechanisms for generating the model's song and what parts of his song are most difficult to produce. We show here that when a vocal mimic, the northern mockingbird, accurately copies the song of another species it also uses the vocal motor pattern employed by the model species. Deviations from the model's production mechanism result in predictable differences in the mockingbird's song. Species-specific acoustic features of the model seem most difficult to copy, suggesting that they have been exposed to the strongest selective pressure to maximize their performance. 相似文献
109.
The crystal structure of a yeast hypothetical protein with sequence similarity to CN hydrolases has been determined to 2.4 A resolution by the multiwavelength anomalous dispersion (MAD) method. The protein folds as a four-layer alphabetabetaalpha sandwich and exists as a dimer in the crystal and in solution. It was selected in a structural genomics project as representative of CN hydrolases at a time when no structures had been determined for members of this family. Structures for two other members of the family have since been reported and the three proteins have similar topology and dimerization modes, which are distinct from those of other alphabetabetaalpha proteins whose structures are known. The dimers form an unusual eight-layer alphabetabetaalpha:alphabetabetaalpha structure. Although the precise enzymatic reactions catalyzed by the yeast protein are not known, considerable information about the active site may be deduced from conserved sequence motifs, comparative biochemical information, and comparison with known structures of hydrolase active sites. As with serine hydrolases, the active-site nucleophile (cysteine in this case) is positioned on a nucleophile elbow. 相似文献
110.