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61.
Novel treatment for joint inflammation 总被引:3,自引:0,他引:3
J T Dingle J L Gordon B L Hazleman C G Knight D P Page Thomas N C Phillips I H Shaw F J Fildes J E Oliver G Jones E H Turner J S Lowe 《Nature》1978,271(5643):372-373
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A physical map of the mouse genome 总被引:1,自引:0,他引:1
Gregory SG Sekhon M Schein J Zhao S Osoegawa K Scott CE Evans RS Burridge PW Cox TV Fox CA Hutton RD Mullenger IR Phillips KJ Smith J Stalker J Threadgold GJ Birney E Wylie K Chinwalla A Wallis J Hillier L Carter J Gaige T Jaeger S Kremitzki C Layman D Maas J McGrane R Mead K Walker R Jones S Smith M Asano J Bosdet I Chan S Chittaranjan S Chiu R Fjell C Fuhrmann D Girn N Gray C Guin R Hsiao L Krzywinski M Kutsche R Lee SS Mathewson C McLeavy C Messervier S Ness S Pandoh P Prabhu AL Saeedi P 《Nature》2002,418(6899):743-750
A physical map of a genome is an essential guide for navigation, allowing the location of any gene or other landmark in the chromosomal DNA. We have constructed a physical map of the mouse genome that contains 296 contigs of overlapping bacterial clones and 16,992 unique markers. The mouse contigs were aligned to the human genome sequence on the basis of 51,486 homology matches, thus enabling use of the conserved synteny (correspondence between chromosome blocks) of the two genomes to accelerate construction of the mouse map. The map provides a framework for assembly of whole-genome shotgun sequence data, and a tile path of clones for generation of the reference sequence. Definition of the human-mouse alignment at this level of resolution enables identification of a mouse clone that corresponds to almost any position in the human genome. The human sequence may be used to facilitate construction of other mammalian genome maps using the same strategy. 相似文献
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Pheromone binding to two rodent urinary proteins revealed by X-ray crystallography. 总被引:12,自引:0,他引:12
Z B?cskei C R Groom D R Flower C E Wright S E Phillips A Cavaggioni J B Findlay A C North 《Nature》1992,360(6400):186-188
The principal protein excreted in male rat urine, urinary alpha 2-globulin and the homologous mouse protein, major urinary protein, have been well characterized, although their functions remain unclear. Male rat urine affects the behaviour and sexual response of female rats, leading to the proposal that rodent urinary proteins are responsible for binding pheromones and their subsequent release from drying urine. Urinary alpha 2-globulin is also involved in hyaline droplet nephropathy, an important toxicological syndrome in male rats resulting from exposure to a number of industrial chemicals and characterized by the accumulation of liganded urinary alpha 2-globulin in lysosomes in the kidney, followed by the induction of renal cancer. We now report the three-dimensional structures of mouse major urinary protein (at 2.4 A resolution) and rat urinary alpha 2-globulin (at 2.8 A resolution). The results corroborate the role of these proteins in pheromone transport and elaborate the structural basis of ligand binding. 相似文献
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Sequence, structure and activity of phosphoglycerate kinase: a possible hinge-bending enzyme. 总被引:20,自引:0,他引:20
R D Banks C C Blake P R Evans R Haser D W Rice G W Hardy M Merrett A W Phillips 《Nature》1979,279(5716):773-777
The fitting of sequenced peptides to a high-resolution X-ray map of phosphoglycerate kinase has yielded the complete sequence and structure of the horse muscle enzyme. Metal ADP and ATP substrates are bound to one of the two widely separated domains in an environment that seems unsuitable for phosphoglycerate binding. The most plausible binding site for the phosphoglycerate substrate is on the other domain about 10 A from the ATP, which implies the possibility of a large scale hinge-bending of the domains to bring the two substrates together in a water-free environment for catalysis. 相似文献
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The four-way (Holliday) DNA junction is the central intermediate in homologous recombination, a ubiquitous process that is important in DNA repair and generation of genetic diversity. The penultimate stage of recombination requires resolution of the DNA junction into nicked-duplex species by the action of a junction-resolving enzyme, examples of which have been identified in a wide variety of organisms. These enzymes are nucleases that are highly selective for the structure of branched DNA. The mechanism of this selectivity has, however, been unclear in the absence of structural data. Here we present the crystal structure of the junction-resolving enzyme phage T7 endonuclease I in complex with a synthetic four-way DNA junction. Although the enzyme is structure-selective, significant induced fit occurs in the interaction, with changes in the structure of both the protein and the junction. The dimeric enzyme presents two binding channels that contact the backbones of the junction's helical arms over seven nucleotides. These interactions effectively measure the relative orientations and positions of the arms of the junction, thereby ensuring that binding is selective for branched DNA that can achieve this geometry. 相似文献