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61.
YUTARO SUZUKI JAN BERGSTRÜM 《Lethaia: An International Journal of Palaeontology and Stratigraphy》1999,32(2):159-172
A major ecological grouping of the trilobites in the Upper Ordovician Boda Limestone buildups in Dalarna is outlined, based primarily on the modes of occurrences in the Jutjärn quarry. The so-called pockets are analysed with regard to their trilobite contents and distribution within a carbonate buildup. The pockets are of two general types. One consists of narrow opened fissures along bedding planes. The matrix of these may contain either of the peculiar blind Isocolus sjoegreni or Ityophorus undulatus , both of which appear to have been cavernous species, possibly belonging to the Bathyuracea (or Leiostegiacea). In addition, small proetids used the fissures for moulting. The other kind of pocket is a cavity largely filled with sediment from the surface of the buildup. The size is considerable, in rare cases up to many tens of cubic metres. Although the buildups housed about 90 trilobite species, each of these pockets is dominated by one or two out of seven large species. Of these, six are illaenids, the seventh the illaenid-like cheirurid Holotrachelus punctillosus. Usually only pygidia and cranidia are found. These species may have lived gregariously around the rims of the cavities. The remaining species, about 85% of the trilobite fauna, appear to have lived on the surface of the buildups. The largest group is the proetids with some 20 species (in addition to those known from pockets). Cheirurinids and lichids contribute with some 15 species each, and there are six odontopleurids. The distinctness of the 'community' is indicated by the circumstance that only three species are shared with contemporaneous level-bottom faunas in Sweden. 相似文献
62.
Isabell Lang Simone Füllsack Agnes Wyzgol Andrea Fick Johannes Trebing José Antonio Carmona Arana Viktoria Sch?fer Daniela Weisenberger Harald Wajant 《The Journal of biological chemistry》2016,291(10):5022-5037
Ligands of the tumor necrosis factor superfamily (TNFSF) interact with members of the TNF receptor superfamily (TNFRSF). TNFSF ligand-TNFRSF receptor interactions have been intensively evaluated by many groups. The affinities of TNFSF ligand-TNFRSF receptor interactions are highly dependent on the oligomerization state of the receptor, and cellular factors (e.g. actin cytoskeleton and lipid rafts) influence the assembly of ligand-receptor complexes, too. Binding studies on TNFSF ligand-TNFRSF receptor interactions were typically performed using cell-free assays with recombinant fusion proteins that contain varying numbers of TNFRSF ectodomains. It is therefore not surprising that affinities determined for an individual TNFSF ligand-TNFRSF interaction differ sometimes by several orders of magnitude and often do not reflect the ligand activity observed in cellular assays. To overcome the intrinsic limitations of cell-free binding studies and usage of recombinant receptor domains, we performed comprehensive binding studies with Gaussia princeps luciferase TNFSF ligand fusion proteins for cell-bound TNFRSF members on intact cells at 37 °C. The affinities of the TNFSF ligand G. princeps luciferase-fusion proteins ranged between 0.01 and 19 nm and offer the currently most comprehensive and best suited panel of affinities for in silico studies of ligand-receptor systems of the TNF family. 相似文献
63.
Cortez L Marino-Buslje C de Jiménez Bonino MB Hellman U 《Biochemical and biophysical research communications》2007,355(1):275-279
The muscle-type nicotinic receptor has two distinguishable acetylcholine binding sites at the alpha-gamma and alpha-delta subunit interfaces; alpha-conotoxins can bind them selectively. Moreover, we previously reported that alpha-conotoxin MI can interact with Torpedo californica and Torpedo marmorata receptors showing that conotoxins can also detect receptors from different species of the same genus [L. Cortez, S.G. del Canto, F. Testai, M.B. de Jiménez Bonino, Conotoxin MI inhibits the acetylcholine binding site of the Torpedo marmorata receptor, Biochem. Biophys. Res. Commun. 295 (2002) 791-795]. Herein, to identify T. marmorata receptor regions involved in alpha-conotoxin MI binding, a photoactivatable reagent was used and labeled sites were mapped by enzymatic proteolysis, MALDI-TOF-MS and Edman degradation. alpha-Conotoxin MI binding determinants were found and studies revealed a second binding motif at the alpha/delta interface. A proposal for receptor-toxin interaction is discussed based on experimental results and docking studies. 相似文献
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66.
Deuterium exchange and mass spectrometry reveal the interaction differences of two synthetic modulators of RXRalpha LBD 下载免费PDF全文
Yan X Pérez E Leid M Schimerlik MI de Lera AR Deinzer ML 《Protein science : a publication of the Protein Society》2007,16(11):2491-2501
Protein amide hydrogen/deuterium (H/D) exchange was used to compare the interactions of two antagonists, UVI 2112 and UVI 3003, with that of the agonist, 9-cis-retinoic acid, upon binding to the human retinoid X receptor alpha ligand-binding domain (hRXRalpha LBD) homodimer. Analysis of the H/D content by mass spectrometry showed that in comparison to 9-cis-retinoic acid, the antagonists provide much greater protection toward deuterium exchange-in throughout the protein, suggesting that the protein-antagonist complex adopts a more restricted conformation or ensemble of conformations in which solvent accesses to amide protons are reduced. A comparison between the two antagonists shows that UVI 3003 is more protective in the C-terminal region due to the extra hydrophobic interactions derived from the atoms in the benzene ring of the carboxylic acid chain. It was less protective within regions comprising peptides 271-278 and 326-330 due to differences in conformational orientation, and/or shorter carboxylic acid chain length. Decreased deuterium exchange-in in the segment 234-239 where the residues do not involve interactions with the ligand was observed with the two antagonists, but not with 9-cis-RA. The amide protons of helix 12 of the agonist- or antagonist-occupied protein in solution have the same deuterium exchange rates as the unliganded protein, supporting a suggestion made previously that helix 12 can cover the occupied binding cavity only with the cofactor present to adjust its location. 相似文献
67.
Yuta Takamura Osamu Shibahara Masaki Watanabe Michiko Fujihara Shoya Yamada Masaru Akehi Takanori Sasaki Hiroyuki Hirano Hiroki Kakuta 《Bioorganic & medicinal chemistry》2019,27(14):3128-3134
Bexarotene (1), a retinoid X receptor (RXR) agonist approved for the treatment of cutaneous T cell lymphoma (CTCL), was reported to migrate into baboon brain based on findings obtained by positron emission tomography (PET) with a 11C-labeled tracer. However, co-administration of non-radioactive 1 had no effect on the distribution of [11C]1, probably due to non-specific binding of 1 as a result of its high lipophilicity. Here, we report a fluorine-18 (18F)-labeled PET tracer [18F]6 derived from RXR partial agonist CBt-PMN (2), which has lower lipophilicity and weaker RXR-binding ability than [11C]1. The concomitant administration of 1 or 2 with [18F]6 with resulted in decreased accumulation of [18F]6 in liver, together with increased brain uptake and increased accumulation in kidney and muscle, as visualized by PET. A plausible explanation of these findings is the inhibition of [18F]6 uptake into the liver by concomitantly administered 1 or 2, leading to an increase in blood concentration of [18F]6 followed by increased accumulation in other tissues. 相似文献
68.
Byerly DW McElroy CA Foster MP 《Protein science : a publication of the Protein Society》2002,11(7):1850-1853
Identifying potential ligand binding sites on a protein surface is an important first step for targeted structure-based drug discovery. While performing control experiments with Escherichia coli peptide deformylase (PDF), we noted that the organic solvents used to solubilize some ligands perturbed many of the same resonances in PDF as the small molecule inhibitors. To further explore this observation, we recorded (15)N HSQC spectra of E. coli peptide deformylase (PDF) in the presence of trace quantities of several simple organic solvents (acetone, DMSO, ethanol, isopropanol) and identified their sites of interaction from local perturbation of amide chemical shifts. Analysis of the protein surface structure revealed that the ligand-induced shift perturbations map to the active site and one additional surface pocket. The correlation between sites of solvent and inhibitor binding highlights the utility of organic solvents to rapidly and effectively validate and characterize binding sites on proteins prior to designing a drug discovery screen. Further, the solvent-induced perturbations have implications for the use of organic solvents to dissolve candidate ligands in NMR-based screens. 相似文献
69.
Ria Gupta Aayushi Mittal Vishesh Agrawal Sushant Gupta Krishan Gupta Rishi Raj Jain Prakriti Garg Sanjay Kumar Mohanty Riya Sogani Harshit Singh Chhabra Vishakha Gautam Tripti Mishra Debarka Sengupta Gaurav Ahuja 《The Journal of biological chemistry》2021,297(2)
The molecular mechanisms of olfaction, or the sense of smell, are relatively underexplored compared with other sensory systems, primarily because of its underlying molecular complexity and the limited availability of dedicated predictive computational tools. Odorant receptors (ORs) allow the detection and discrimination of a myriad of odorant molecules and therefore mediate the first step of the olfactory signaling cascade. To date, odorant (or agonist) information for the majority of these receptors is still unknown, limiting our understanding of their functional relevance in odor-induced behavioral responses. In this study, we introduce OdoriFy, a Web server featuring powerful deep neural network–based prediction engines. OdoriFy enables (1) identification of odorant molecules for wildtype or mutant human ORs (Odor Finder); (2) classification of user-provided chemicals as odorants/nonodorants (Odorant Predictor); (3) identification of responsive ORs for a query odorant (OR Finder); and (4) interaction validation using Odorant–OR Pair Analysis. In addition, OdoriFy provides the rationale behind every prediction it makes by leveraging explainable artificial intelligence. This module highlights the basis of the prediction of odorants/nonodorants at atomic resolution and for the ORs at amino acid levels. A key distinguishing feature of OdoriFy is that it is built on a comprehensive repertoire of manually curated information of human ORs with their known agonists and nonagonists, making it a highly interactive and resource-enriched Web server. Moreover, comparative analysis of OdoriFy predictions with an alternative structure-based ligand interaction method revealed comparable results. OdoriFy is available freely as a web service at https://odorify.ahujalab.iiitd.edu.in/olfy/. 相似文献
70.
Elaine E. Thompson Alexandr P. Kornev Natarajan Kannan Choel Kim Lynn F. Ten Eyck Susan S. Taylor 《Protein science : a publication of the Protein Society》2009,18(10):2016-2026
Identifying conserved pockets on the surfaces of a family of proteins can provide insight into conserved geometric features and sites of protein–protein interaction. Here we describe mapping and comparison of the surfaces of aligned crystallographic structures, using the protein kinase family as a model. Pockets are rapidly computed using two computer programs, FADE and Crevasse. FADE uses gradients of atomic density to locate grooves and pockets on the molecular surface. Crevasse, a new piece of software, splits the FADE output into distinct pockets. The computation was run on 10 kinase catalytic cores aligned on the αF‐helix, and the resulting pockets spatially clustered. The active site cleft appears as a large, contiguous site that can be subdivided into nucleotide and substrate docking sites. Substrate specificity determinants in the active site cleft between serine/threonine and tyrosine kinases are visible and distinct. The active site clefts cluster tightly, showing a conserved spatial relationship between the active site and αF‐helix in the C‐lobe. When the αC‐helix is examined, there are multiple mechanisms for anchoring the helix using spatially conserved docking sites. A novel site at the top of the N‐lobe is present in all the kinases, and there is a large conserved pocket over the hinge and the αC‐β4 loop. Other pockets on the kinase core are strongly conserved but have not yet been mapped to a protein–protein interaction. Sites identified by this algorithm have revealed structural and spatially conserved features of the kinase family and potential conserved intermolecular and intramolecular binding sites. 相似文献