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91.
The Eph family is the largest known group of structurally related receptor tyrosine kinases (RTKs). Each Eph receptor has a specific Ephrin ligand, and these function to define spatial boundaries during development. Analyses of EphA4 in mouse, chick, frog and zebrafish embryos have implicated this gene in a number of developmental processes, including maintenance of segmental boundaries, axon guidance, limb development, neural crest migration and patterning of the ear. In order to determine which components of EphA4 function may be primitive for gnathostomes, we cloned EphA4 from the lesser spotted catshark (Scyliorhinus canicula) and examined its expression pattern during shark embryonic development. Consistent with the patterns reported for bony fish and tetrapods, we observed segmental expression of EphA4 in the developing hindbrain and later in the pharyngeal arches of shark embryos. EphA4 was also detected during sensory organogenesis, in the developing ear, eye, nasal pits and lateral line. A dynamic pattern of EphA4 expression occurs during shark fin development, suggesting an early role in outgrowth and patterning of the fin buds and a later role in tissue differentiation. We also observed several novel domains of EphA4 expression that have not been reported in other vertebrates, including external gill buds, dermal denticles, median fins and claspers. While some of these domains may reflect co-option of EphA4 expression to novel sites for development of shark-specific characters, others are more likely to be ancestral patterns of expression that were lost in other vertebrate lineages.Edited by R. P. Elinson 相似文献
92.
Kwiecień RA Rostkowski M Dybała-Defratyka A Paneth P 《Journal of inorganic biochemistry》2004,98(6):1078-1086
Several semiempirical methods (MNDO-d, PM3tm, PM3-d, PM5, PM6, and AM1-d) have been tested against experimental data and density functional theory (DFT) results in search for the best methods that can be used for quantum-mechanical-molecular mechanics (QM/MM) modeling of corrinoid systems of vitamin B(12) co-factor. It has been found that the PM6 parametrization in its present form gives results closest to hybrid DFT calculations that are most widely used thus far. In comparison with pure DFT and experimental data the best agreement is obtained for PM3tm parametrization, while PM6 yields slightly worse results. AM1-d yields bad geometry of the corrin moiety. The worst performance was observed for MNDO-d, which has severe problem with position and orientation of the alpha-ligands. 相似文献
93.
Heasley BH Jarosz R Carter KM Van SJ Lynch KR Macdonald TL 《Bioorganic & medicinal chemistry letters》2004,14(15):4069-4074
A recently reported dual LPA(1)/LPA(3) receptor antagonist (1) has been modified so as to modulate the basicity, sterics, and dipole moment of the 2-pyridyl moiety. Additionally, the implications of installing nonhydrolyzable phosphate head group isosteres with regard to antagonist potency and selectivity at LPA receptors is described. This study has resulted in the development of the first nonhydrolyzable and presumably phosphatase-resistant LPA(3)-selective antagonist reported to date. 相似文献
94.
Basto R Scaerou F Mische S Wojcik E Lefebvre C Gomes R Hays T Karess R 《Current biology : CB》2004,14(1):56-61
Rough Deal (Rod) and Zw10 are components of a complex required for the metazoan metaphase checkpoint and for recruitment of dynein/dynactin to the kinetochore. The Rod complex, like most classical metaphase checkpoint components, forms part of the outer domain of unattached kinetochores. Here we analyze the dynamics of a GFP-Rod chimera in living syncytial Drosophila embryos. Uniquely among checkpoint proteins, GFP-Rod robustly streams from kinetochores along microtubules, from the time of chromosome attachment until anaphase onset. Prometaphase and metaphase kinetochores continuously recruit new Rod, thus feeding the current. Rod flux from kinetochores appears to require biorientation but not tension because it continues in the presence of taxol. As with Mad2, kinetochore- and spindle-associated Rod rapidly turns over with free cytosolic Rod, both during normal mitosis and after colchicine treatment, with a t1/2 of 25-45 s. GFP-Rod coimmunoprecipitates with dynein/dynactin, and in the absence of microtubules both Rod and dynactin accumulate on kinetochores. Nevertheless, Rod and dynein/dynactin behavior are distinguishable. We propose that the Rod complex is a major component of the fibrous corona and that the recruitment of Rod during metaphase is required to replenish kinetochore dynein after checkpoint conditions have been satisfied but before anaphase onset. 相似文献
95.
Nautiloids, the externally shelled cephalopods of Cambrian origin, are the most ancient lineage among extant cephalopods. Their ancestral characters are explored based on morphological and molecular data (18S rDNA sequence) to investigate the evolution of present cephalopod lineages. Among molluscs, nautilus 18S rDNA gene is the longest reported so far, due to large nucleotidic insertions. By comparison with other 18S sequences, the complete gene of N. macromphalus helps to clarify the taxonomic status of the three universally recognised Nautilus species. The range of interspecific molecular differences supports separation of the present species into two surviving ectocochleate genera, Nautilus and Allonautilus. Nautiloid 18S is considered as corresponding to the ancestral form of 18S as is the number of chromosomes in Nautilus (52), the lowest among cephalopods. Comparison of karyological characteristics amongst cephalopods in a phylogenetic context suggests a possible correlation between duplication events and lineage divergence. 相似文献
96.
Rzychon M Filipek R Sabat A Kosowska K Dubin A Potempa J Bochtler M 《Protein science : a publication of the Protein Society》2003,12(10):2252-2256
Staphostatins are the endogenous inhibitors of the major secreted cysteine proteases of Staphylococcus aureus, the staphopains. Here, we present the 1.4 A crystal structure of staphostatin B and show that the fold can be described as a fully closed, highly sheared eight-stranded beta-barrel. Thus, staphostatin B is related to beta-barrel domains that are involved in the inhibition or regulation of proteases of various catalytic types and to the superfamily of lipocalins/cytosolic fatty acid binding proteins. Unexpectedly for a cysteine protease inhibitor, staphostatin B is not significantly similar to cystatins. 相似文献
97.
Ellerby HM Lee S Ellerby LM Chen S Kiyota T del Rio G Sugihara G Sun Y Bredesen DE Arap W Pasqualini R 《The Journal of biological chemistry》2003,278(37):35311-35316
Protein engineering is an emerging area that has expanded our understanding of protein folding and laid the groundwork for the creation of unprecedented structures with unique functions. We previously designed the first native-like pore-forming protein, small globular protein (SGP). We show here that this artificially engineered protein has membrane-disrupting properties and anti-tumor activity in several cancer animal models. We propose and validate a mechanism for the selectivity of SGP toward cell membranes in tumors. SGP is the prototype for a new class of artificial proteins designed for therapeutic applications. 相似文献
98.
99.
A new RNase-based immunoconjugate selectively cytotoxic for ErbB2-overexpressing cells 总被引:5,自引:0,他引:5
We report a new tumor-directed immunoRNase, a chimeric protein made up of an antibody fragment (single-chain Fv fragment) directed to ErbB2, a cell surface receptor, and a non-toxic, human ribonuclease, which upon cell internalization becomes cytotoxic. The immunoRNase is active as a ribonuclease, specifically binds and selectively kills ErbB2-positive cells. ErbB2 is one of the most specific tumor-associated antigens identified so far, overexpressed on tumor cells of different origin. Its choice as target antigen and that of a non-toxic, human RNase as the killer moiety makes this immunoRNase a new, potentially attractive anticancer agent. 相似文献
100.
Triosephosphate isomerase (TIM) has a conserved salt bridge 20 A away from both the active site and the dimer interface. In this study, four salt bridge mutants of Trypanosoma brucei brucei TIM were characterized. The folding and stability of the mutants are impaired compared to the wild-type enzyme. This salt bridge is part of a hydrogen bonding network which tethers the C-terminal beta7alpha7beta8alpha8 unit to the bulk of the protein. In the variants D227N, D227A, and R191S, this network is preserved, as can be deduced from the structure of the R191S variant. In the R191A variant, the side chain at position 191 cannot contribute to this network. Also the catalytic power of this variant is most affected. 相似文献