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排序方式: 共有60条查询结果,搜索用时 218 毫秒
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I. I. Protasevich A. L. Platonov A. G. Pavlovsky N. G. Esipova 《Journal of biomolecular structure & dynamics》2013,31(5):885-893
Abstract A correlation between the distribution of charged side groups in the globule of Bacillus intermedius 7P ribonuclease (binase) and the process of heat denaturation was studied at different pH values in order to estimate a relation between charge distribution in globular proteins and the character of cooperative thermodynamic transitions. As was shown by comparing the results of scanning microcalorimetric analysis of heat denaturation with the three-dimentional structure of binase, at optimal pH the molecule exists as a single cooperative system stabilized by hydrogen bonds, Van der Waals' contacts, and electrostatic interactions like salt bridges. At pH lower than 4.0 (below the physiological optimum) the cooperativity type of the system was found to change due to a reversible cooperative transition in the ternary structure of the protein globule. It has been concluded that the molecular architecture and the arrangement of atoms do not change considerably in different environments; thus the thermodynamic properties of the globule vary due to the alteration of charge distribution and the consequent changes in the size and number of cooperative regions of the globule. Thus, structural and energetic domains may be non-coincident in proteins. 相似文献
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Pfefferkorn JA Song Y Sun KL Miller SR Trivedi BK Choi C Sorenson RJ Bratton LD Unangst PC Larsen SD Poel TJ Cheng XM Lee C Erasga N Auerbach B Askew V Dillon L Hanselman JC Lin Z Lu G Robertson A Olsen K Mertz T Sekerke C Pavlovsky A Harris MS Bainbridge G Caspers N Chen H Eberstadt M 《Bioorganic & medicinal chemistry letters》2007,17(16):4538-4544
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Nousbeck J Burger B Fuchs-Telem D Pavlovsky M Fenig S Sarig O Itin P Sprecher E 《American journal of human genetics》2011,(2):4017-307
Monogenic disorders offer unique opportunities for researchers to shed light upon fundamental physiological processes in humans. We investigated a large family affected with autosomal-dominant adermatoglyphia (absence of fingerprints) also known as the "immigration delay disease." Using linkage and haplotype analyses, we mapped the disease phenotype to 4q22. One of the genes located in this interval is SMARCAD1, a member of the SNF subfamily of the helicase protein superfamily. We demonstrated the existence of a short isoform of SMARCAD1 exclusively expressed in the skin. Sequencing of all SMARCAD1 coding and noncoding exons revealed a heterozygous transversion predicted to disrupt a conserved donor splice site adjacent to the 3' end of a noncoding exon uniquely present in the skin-specific short isoform of the gene. This mutation segregated with the disease phenotype throughout the entire family. Using a minigene system, we found that this mutation causes aberrant splicing, resulting in decreased stability of the short RNA isoform as predicted by computational analysis and shown by RT-PCR. Taken together, the present findings implicate a skin-specific isoform of SMARCAD1 in the regulation of dermatoglyph development. 相似文献
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Most strains of Drosophila pseudoobscura are neutral to light when tested in phototactic mazes. However, clear-cut photopositive and photogenative populations are obtained by selection over a series of generations. The genetic nature of the differences between the positive and negative populations has been studied in crosses in which the three large autosomes carried mutant markers. All chromosomes contain genes which influence the response to light. The third chromosome has the strongest effect, followed by the second, the X, and the fourth chromosomes. This seriation is not in proportion to the relative lengths of the chromosomes. Either the effective genes are not very numerous, or some of them exert stronger influences than others. 相似文献
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Warmus JS Flamme C Zhang LY Barrett S Bridges A Chen H Gowan R Kaufman M Sebolt-Leopold J Leopold W Merriman R Ohren J Pavlovsky A Przybranowski S Tecle H Valik H Whitehead C Zhang E 《Bioorganic & medicinal chemistry letters》2008,18(23):6171-6174
This paper reports a second generation MEK inhibitor. The previously reported potent and efficacious MEK inhibitor, PD-184352 (CI-1040), contains an integral hydroxamate moiety. This compound suffered from less than ideal solubility and metabolic stability. An oxadiazole moiety behaves as a bioisostere for the hydroxamate group, leading to a more metabolically stable and efficacious MEK inhibitor. 相似文献
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X-ray structure of human stromelysin catalytic domain complexed with nonpeptide inhibitors: implications for inhibitor selectivity.
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A. G. Pavlovsky M. G. Williams Q. Z. Ye D. F. Ortwine C. F. Purchase nd A. D. White V. Dhanaraj B. D. Roth L. L. Johnson D. Hupe C. Humblet T. L. Blundell 《Protein science : a publication of the Protein Society》1999,8(7):1455-1462
Effective inhibitors of matrix metalloproteinases (MMPs), a family of connective tissue-degrading enzymes, could be useful for the treatment of diseases such as cancer, multiple sclerosis, and arthritis. Many of the known MMP inhibitors are derived from peptide substrates, with high potency in vitro but little selectivity among MMPs and poor bioavailability. We have discovered nonpeptidic MMP inhibitors with improved properties, and report here the crystal structures of human stromelysin-1 catalytic domain (SCD) complexed with four of these inhibitors. The structures were determined and refined at resolutions ranging from 1.64 to 2.0 A. Each inhibitor binds in the active site of SCD such that a bulky diphenyl piperidine moiety penetrates a deep, predominantly hydrophobic S'1 pocket. The active site structure of the SCD is similar in all four inhibitor complexes, but differs substantially from the peptide hydroxamate complex, which has a smaller side chain bound in the S'1 pocket. The largest differences occur in the loop forming the "top" of this pocket. The occupation of these nonpeptidic inhibitors in the S'1 pocket provides a structural basis to explain their selectivity among MMPs. An analysis of the unique binding mode predicts structural modifications to design improved MMP inhibitors. 相似文献