Base de dados : MEDLINE
Pesquisa : B01.050.150.900.493.370.935 [Categoria DeCS]
Referências encontradas : 2828 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 283 ir para página                         

  1 / 2828 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28878016
[Au] Autor:Yu Z; Cohen JB
[Ad] Endereço:From the Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.
[Ti] Título:Enantiomeric barbiturates bind distinct inter- and intrasubunit binding sites in a nicotinic acetylcholine receptor (nAChR).
[So] Source:J Biol Chem;292(42):17258-17271, 2017 Oct 20.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nicotinic acetylcholine receptors (nAChRs) and γ-aminobutyric acid type A receptors (GABA Rs) are members of the pentameric ligand-gated ion channel superfamily. Drugs acting as positive allosteric modulators of muscle-type α ßγδ nAChRs, of use in treatment of neuromuscular disorders, have been hard to identify. However, identification of nAChR allosteric modulator binding sites has been facilitated by using drugs developed as photoreactive GABA R modulators. Recently, 1-methyl-5-allyl-5-( -trifluoromethyl-diazirinylphenyl) barbituric acid ( TFD-MPAB), an anesthetic and GABA R potentiator, has been shown to inhibit α ßγδ nAChRs, binding in the ion channel and to a γ -α subunit interface site similar to its GABA R intersubunit binding site. In contrast, 1-methyl-5-propyl-5-( -trifluoromethyl-diazirinylphenyl) barbituric acid ( TFD-MPPB) acts as a convulsant and GABA R inhibitor. Photolabeling studies established that TFD-MPPB binds to the same GABA R intersubunit binding site as TFD-MPAB, but with negative rather than positive energetic coupling to GABA binding. We now show that TFD-MPPB binds with the same state (agonist) dependence as TFD-MPAB within the nAChR ion channel, but it does not bind to the intersubunit binding site. Rather, TFD-MPPB binds to intrasubunit sites within the α and δ subunits, photolabeling αVal-218 (αM1), δPhe-232 (δM1), δThr-274 (δM2), and δIle-288 (δM3). Propofol, a general anesthetic that binds to GABA R intersubunit sites, inhibited [ H] TFD-MPPB photolabeling of these nAChR intrasubunit binding sites. These results demonstrate that in an nAChR, the subtle difference in structure between TFD-MPPB and TFD-MPAB (chirality; 5-propyl 5-allyl) determines selectivity for intra- intersubunit sites, in contrast to GABA Rs, where this difference affects state dependence of binding to a common site.
[Mh] Termos MeSH primário: Barbitúricos/química
Proteínas de Peixes/química
Receptores de GABA-A/química
Receptores Nicotínicos/química
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação
Propofol/química
Subunidades Proteicas
Torpedo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Barbiturates); 0 (Fish Proteins); 0 (Protein Subunits); 0 (Receptors, GABA-A); 0 (Receptors, Nicotinic); YI7VU623SF (Propofol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171028
[Lr] Data última revisão:
171028
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170908
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.808592


  2 / 2828 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27871840
[Au] Autor:Sun J; Comeau JF; Baenziger JE
[Ad] Endereço:Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, 451 Smyth Rd, K1H 8M5 Ottawa, ON, Canada.
[Ti] Título:Probing the structure of the uncoupled nicotinic acetylcholine receptor.
[So] Source:Biochim Biophys Acta;1859(2):146-154, 2017 02.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:In the absence of activating anionic lipids and cholesterol, the nicotinic acetylcholine receptor (nAChR) from Torpedo adopts an uncoupled conformation that does not usually gate open in response to agonist. The uncoupled conformation binds both agonists and non-competitive channel blockers with a lower affinity than the desensitized state, consistent with both the extracellular agonist-binding and transmembrane channel-gating domains individually adopting resting-state like conformations. To test this hypothesis, we characterized the binding of the agonist, acetylcholine, and two fluorescent channel blockers, ethidium and crystal violet, to resting, desensitized and uncoupled nAChRs in reconstituted membranes. The measured K for acetylcholine binding to the uncoupled nAChR is similar to that for the resting state, confirming that the agonist binding site adopts a resting-state like conformation. Although both ethidium and crystal violet bind to the resting and desensitized channel pores with distinct affinities, no binding of either probe was detected to the uncoupled nAChR. Our data suggest that the transmembrane domain of the uncoupled nAChR adopts a conformation distinct from that of the resting and desensitized states. The lack of binding is consistent with a more constricted channel pore, possibly along the lines of what is observed in crystal structures of the prokaryotic homolog, ELIC.
[Mh] Termos MeSH primário: Receptores Nicotínicos/química
Receptores Nicotínicos/metabolismo
[Mh] Termos MeSH secundário: Acetilcolina/metabolismo
Animais
Sítios de Ligação/fisiologia
Membrana Celular/fisiologia
Colesterol/metabolismo
Bicamadas Lipídicas/química
Bicamadas Lipídicas/metabolismo
Modelos Moleculares
Ligação Proteica/fisiologia
Conformação Proteica
Espectroscopia de Infravermelho com Transformada de Fourier/métodos
Torpedo/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Lipid Bilayers); 0 (Receptors, Nicotinic); 97C5T2UQ7J (Cholesterol); N9YNS0M02X (Acetylcholine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161123
[St] Status:MEDLINE


  3 / 2828 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:27817023
[Au] Autor:Kasheverov IE; Kryukova EV; Kudryavtsev DS; Ivanov IA; Egorova NV; Zhmak MN; Spirova EN; Shelukhina IV; Odinokov AV; Alfimov MV; Tsetlin VI
[Ad] Endereço:Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997, Russia.
[Ti] Título:Analysis of binding centers in nicotinic receptors with the aid of synthetic peptides.
[So] Source:Dokl Biochem Biophys;470(1):338-341, 2016 Sep.
[Is] ISSN:1608-3091
[Cp] País de publicação:Russia (Federation)
[La] Idioma:eng
[Ab] Resumo:We studies the receptor-binding specificity of the synthetic peptide HAP (High Affinity Peptide) and its analogues, which are regarded as a model of the orthosteric site nicotinic acetylcholine receptors (nAChR). Using radioligand analysis, electrophysiology tests, and calcium imaging, we assessed the ability of HAP to interact with nAChR antagonists: long α-neurotoxins and α-conotoxins. A high affinity of HAP for α-bungarotoxin and the absence of its interaction with α-cobratoxin and α-conotoxins was found. The synthesized analogues of HAP in general retained the properties of the original peptide. Thus, HAP cannot be a model of a ligand-binding site.
[Mh] Termos MeSH primário: Colinérgicos/farmacologia
Fragmentos de Peptídeos/metabolismo
Receptores Nicotínicos/metabolismo
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação
Bungarotoxinas/farmacologia
Cálcio/metabolismo
Linhagem Celular
Conotoxinas/metabolismo
Conotoxinas/farmacologia
Seres Humanos
Potenciais da Membrana/efeitos dos fármacos
Potenciais da Membrana/fisiologia
Camundongos
Modelos Moleculares
Neurotoxinas/metabolismo
Neurotoxinas/farmacologia
Oócitos
Técnicas de Patch-Clamp
Fragmentos de Peptídeos/síntese química
Fragmentos de Peptídeos/química
Biblioteca de Peptídeos
Ensaio Radioligante
Ratos
Receptores Nicotínicos/química
Receptores Nicotínicos/genética
Torpedo
Imagens com Corantes Sensíveis à Voltagem
Xenopus laevis
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bungarotoxins); 0 (Cholinergic Agents); 0 (Conotoxins); 0 (Neurotoxins); 0 (Peptide Fragments); 0 (Peptide Library); 0 (Receptors, Nicotinic); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161107
[St] Status:MEDLINE


  4 / 2828 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27563924
[Au] Autor:Couesnon A; Aráoz R; Iorga BI; Benoit E; Reynaud M; Servent D; Molgó J
[Ad] Endereço:Institut des Neurosciences Paris-Saclay, UMR 9197 CNRS/Université Paris-Sud, F-91190 Gif-sur-Yvette, France. aurelie.couesnon@inaf.cnrs-gif.fr.
[Ti] Título:The Dinoflagellate Toxin 20-Methyl Spirolide-G Potently Blocks Skeletal Muscle and Neuronal Nicotinic Acetylcholine Receptors.
[So] Source:Toxins (Basel);8(9), 2016 08 24.
[Is] ISSN:2072-6651
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:The cyclic imine toxin 20-methyl spirolide G (20-meSPX-G), produced by the toxigenic dinoflagellate Alexandrium ostenfeldii/Alexandrium peruvianum, has been previously reported to contaminate shellfish in various European coastal locations, as revealed by mouse toxicity bioassay. The aim of the present study was to determine its toxicological profile and its molecular target selectivity. 20-meSPX-G blocked nerve-evoked isometric contractions in isolated mouse neuromuscular preparations, while it had no action on contractions elicited by direct electrical stimulation, and reduced reversibly nerve-evoked compound muscle action potential amplitudes in anesthetized mice. Voltage-clamp recordings in Xenopus oocytes revealed that 20-meSPX-G potently inhibited currents evoked by ACh on Torpedo muscle-type and human α7 nicotinic acetylcholine receptors (nAChR), whereas lower potency was observed in human α4ß2 nAChR. Competition-binding assays showed that 20-meSPX-G fully displaced [³H]epibatidine binding to HEK-293 cells expressing the human α3ß2 (Ki = 0.040 nM), whereas a 90-fold lower affinity was detected in human α4ß2 nAChR. The spirolide displaced [(125)I]α-bungarotoxin binding to Torpedo membranes (Ki = 0.028 nM) and in HEK-293 cells expressing chick chimeric α7-5HT3 nAChR (Ki = 0.11 nM). In conclusion, this is the first study to demonstrate that 20-meSPX-G is a potent antagonist of nAChRs, and its subtype selectivity is discussed on the basis of molecular docking models.
[Mh] Termos MeSH primário: Fibras Colinérgicas/efeitos dos fármacos
Contração Isométrica/efeitos dos fármacos
Músculo Esquelético/efeitos dos fármacos
Junção Neuromuscular/efeitos dos fármacos
Antagonistas Nicotínicos/toxicidade
Receptores Nicotínicos/efeitos dos fármacos
Compostos de Espiro/toxicidade
[Mh] Termos MeSH secundário: Potenciais de Ação
Animais
Sítios de Ligação
Ligação Competitiva
Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo
Galinhas
Fibras Colinérgicas/metabolismo
Relação Dose-Resposta a Droga
Estimulação Elétrica
Feminino
Células HEK293
Seres Humanos
Técnicas In Vitro
Camundongos
Simulação de Acoplamento Molecular
Músculo Esquelético/inervação
Músculo Esquelético/metabolismo
Junção Neuromuscular/metabolismo
Antagonistas Nicotínicos/química
Antagonistas Nicotínicos/metabolismo
Ligação Proteica
Conformação Proteica
Piridinas/metabolismo
Receptores Nicotínicos/química
Receptores Nicotínicos/genética
Receptores Nicotínicos/metabolismo
Compostos de Espiro/química
Compostos de Espiro/metabolismo
Relação Estrutura-Atividade
Torpedo
Transfecção
Xenopus laevis
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (20-methyl spirolide G); 0 (Bridged Bicyclo Compounds, Heterocyclic); 0 (Nicotinic Antagonists); 0 (Pyridines); 0 (Receptors, Nicotinic); 0 (Spiro Compounds); M6K314F1XX (epibatidine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171122
[Lr] Data última revisão:
171122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160827
[St] Status:MEDLINE


  5 / 2828 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27509403
[Au] Autor:Bolognini L; Leoni S; Polidori P; Grati F; Scarcella G; Pellini G; Domenichetti F; Ferrà C; Fabi G
[Ad] Endereço:Institute of Marine Sciences (ISMAR), National Research Council (CNR), Largo Fiera della Pesca, 60125, Ancona, Italy.
[Ti] Título:Occurrence of the Leech, Pontobdella muricata Linnaeus, on Elasmobranch Species in the Northern and Central Adriatic Sea.
[So] Source:J Parasitol;102(6):643-645, 2016 Dec.
[Is] ISSN:1937-2345
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This study provides a parasitological analysis of the elasmobranch species caught in the northern and central Adriatic Sea. Sixty-two marine leeches were recorded on 747 individuals of Raja clavata Linnaeus, 1758 (thornback ray), Myliobatis aquila Linnaeus, 1758 (common eagle ray), and Torpedo marmorata Risso, 1810 (marbled torpedo ray) caught in 56 hauls over a 5 yr period. All leeches were identified as Pontobdella muricata, which is a typical ectoparasite of benthic elasmobranchs. The prevalence of infection ranged from 7.11% on R. clavata to 12.00% on M. aquila. The intensity of infection, the preferential sites of attachment to the host, and the periodicity of infection were evaluated.
[Mh] Termos MeSH primário: Ectoparasitoses/veterinária
Doenças dos Peixes/parasitologia
Sanguessugas/fisiologia
Raias/parasitologia
Torpedo/parasitologia
[Mh] Termos MeSH secundário: Animais
Ectoparasitoses/epidemiologia
Ectoparasitoses/parasitologia
Doenças dos Peixes/epidemiologia
Mar Mediterrâneo/epidemiologia
Prevalência
Estações do Ano
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170512
[Lr] Data última revisão:
170512
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160811
[St] Status:MEDLINE
[do] DOI:10.1645/15-826


  6 / 2828 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27395617
[Au] Autor:Carvalho MR; White WT
[Ad] Endereço:Departamento de Zoologia, Instituto de Biociências, Universidade de São Paulo, Rua do Matão, Trav. 14, no. 101, 05508-090, São Paulo, SP, Brazil.; Email: mrcarvalho@ib.usp.br.
[Ti] Título:Narcine baliensis, a new species of electric ray from southeast Asia (Chondrichthyes: Torpediniformes).
[So] Source:Zootaxa;4127(1):149-60, 2016 Jun 22.
[Is] ISSN:1175-5334
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:A new species of numbfish, Narcine baliensis, sp. nov., is described from the tropical eastern Indian Ocean from Indonesia. It is superficially similar to N. brevilabiata and N. atzi in aspects of its color pattern, but is distinguished from both congeners in details of its color pattern, in tooth band morphology, and in proportions of its dorsal fins, among other features. Narcine baliensis, sp. nov., is unique in having a dorsal color pattern composed of large, circular, ovoid or elongate dark brown spots or blotches on dorsal disc along with more numerous small (about eye-sized or slightly greater) brownish, subcircular spots, with large blotches and small spots surrounded by a very slender creamy-white pattern, as well as in having broadly circular upper and lower tooth bands of about the same width and shape. The genus Narcine is now composed of 20 valid species, but uncertainty remains concerning the identification and morphological variation of some of its species in the tropical Indo-West Pacific region.
[Mh] Termos MeSH primário: Torpedo/classificação
[Mh] Termos MeSH secundário: Distribuição Animal
Estruturas Animais/anatomia & histologia
Estruturas Animais/crescimento & desenvolvimento
Animais
Tamanho Corporal
Ecossistema
Feminino
Oceano Índico
Indonésia
Masculino
Tamanho do Órgão
Torpedo/anatomia & histologia
Torpedo/crescimento & desenvolvimento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170306
[Lr] Data última revisão:
170306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160711
[St] Status:MEDLINE
[do] DOI:10.11646/zootaxa.4127.1.8


  7 / 2828 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27249963
[Au] Autor:Vaughan DB; Chisholm LA; Hansen H
[Ad] Endereço:Marine Parasitology Laboratory, Centre for Sustainable Tropical Fisheries and Aquaculture, College of Marine and Environmental Sciences, James Cook University, Queensland, 4810, Australia. david.vaughan@my.jcu.edu.au.
[Ti] Título:Electrocotyle whittingtoni n. gen., n. sp. (Monogenea: Monocotylidae: Heterocotylinae) from the gills of a captive onefin electric ray, Narke capensis (Narkidae) at Two Oceans Aquarium, Cape Town, South Africa.
[So] Source:Parasitol Res;115(9):3575-84, 2016 Sep.
[Is] ISSN:1432-1955
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Electrocotyle whittingtoni n. gen., n. sp. (Monogenea: Monocotylidae) is described from the gills of a captive female onefin electric ray, Narke capensis, collected for exhibition at Two Oceans Aquarium in Cape Town, South Africa. Electrocotyle n. gen. is most similar to the heterocotyline genera Heterocotyle and Potamotrygonocotyle but could not be accommodated easily in either of these groups. The new genus is characterised by a haptor with one central and eight peripheral loculi, four unsclerotised structures on the dorsal surface of the haptor, a single unsclerotised non-sinous ridge on the ventral surface of the haptoral septa, large hamuli with a long handle and reduced guard, a vagina with sclerotised walls, and tetrahedral eggs. Molecular phylogenetic analyses based on 28S sequences strongly support the separate genus status of Electrocotyle n. gen and thus support our morphological conclusion. The Heterocotylinae is amended to accommodate the new genus, and the new species is fully described and illustrated herein. This is the first record of a monocotylid from the Narkidae. Electrocotyle whittingtoni n. gen. n. sp. is considered potentially pathogenic given its negative impact on the health of its captive host kept in the quarantine facility at Two Oceans Aquarium.
[Mh] Termos MeSH primário: Doenças dos Peixes/parasitologia
Torpedo/parasitologia
Trematódeos/isolamento & purificação
Infecções por Trematódeos/veterinária
[Mh] Termos MeSH secundário: Animais
Feminino
Brânquias/parasitologia
Oceanos e Mares
Filogenia
África do Sul
Trematódeos/classificação
Infecções por Trematódeos/parasitologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171007
[Lr] Data última revisão:
171007
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160603
[St] Status:MEDLINE
[do] DOI:10.1007/s00436-016-5123-1


  8 / 2828 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:27054065
[Au] Autor:Zheng F; Robertson AP; Abongwa M; Yu EW; Martin RJ
[Ad] Endereço:Department of Chemistry, College of Liberal Arts and Sciences, Iowa State University, Ames, IA 50011, USA.
[Ti] Título:The Ascaris suum nicotinic receptor, ACR-16, as a drug target: Four novel negative allosteric modulators from virtual screening.
[So] Source:Int J Parasitol Drugs Drug Resist;6(1):60-73, 2016 Apr.
[Is] ISSN:2211-3207
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Soil-transmitted helminth infections in humans and livestock cause significant debility, reduced productivity and economic losses globally. There are a limited number of effective anthelmintic drugs available for treating helminths infections, and their frequent use has led to the development of resistance in many parasite species. There is an urgent need for novel therapeutic drugs for treating these parasites. We have chosen the ACR-16 nicotinic acetylcholine receptor of Ascaris suum (Asu-ACR-16), as a drug target and have developed three-dimensional models of this transmembrane protein receptor to facilitate the search for new bioactive compounds. Using the human α7 nAChR chimeras and Torpedo marmorata nAChR for homology modeling, we defined orthosteric and allosteric binding sites on the Asu-ACR-16 receptor for virtual screening. We identified four ligands that bind to sites on Asu-ACR-16 and tested their activity using electrophysiological recording from Asu-ACR-16 receptors expressed in Xenopus oocytes. The four ligands were acetylcholine inhibitors (SB-277011-A, IC50, 3.12 ± 1.29 µM; (+)-butaclamol Cl, IC50, 9.85 ± 2.37 µM; fmoc-1, IC50, 10.00 ± 1.38 µM; fmoc-2, IC50, 16.67 ± 1.95 µM) that behaved like negative allosteric modulators. Our work illustrates a structure-based in silico screening method for seeking anthelmintic hits, which can then be tested electrophysiologically for further characterization.
[Mh] Termos MeSH primário: Ascaris suum/anatomia & histologia
Ascaris suum/efeitos dos fármacos
Ascaris suum/metabolismo
Descoberta de Drogas/métodos
Agonistas Nicotínicos/metabolismo
Agonistas Nicotínicos/farmacologia
Receptores Nicotínicos/química
Receptores Nicotínicos/metabolismo
[Mh] Termos MeSH secundário: Regulação Alostérica
Sítio Alostérico/genética
Animais
Ascaris suum/genética
Sítios de Ligação/genética
Butaclamol/farmacologia
Simulação por Computador
Sistemas de Liberação de Medicamentos
Fluorenos/metabolismo
Fluorenos/farmacologia
Seres Humanos
Concentração Inibidora 50
Ácidos Isonipecóticos/metabolismo
Ácidos Isonipecóticos/farmacologia
Ligantes
Modelos Moleculares
Agonistas Nicotínicos/química
Nitrilos/farmacologia
Oócitos
Técnicas de Patch-Clamp
Tetra-Hidroisoquinolinas/farmacologia
Torpedo/genética
Torpedo/fisiologia
Xenopus/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (9-fluorenylmethoxycarbonyl-4-(naphthalen-1-yl)-piperidine-4-carboxylic acid); 0 (9-fluorenylmethoxycarbonyl-4-(naphthalen-2-yl)piperidine-4-carboxylic acid); 0 (Fluorenes); 0 (Isonipecotic Acids); 0 (Ligands); 0 (Nicotinic Agonists); 0 (Nitriles); 0 (Receptors, Nicotinic); 0 (SB 277011); 0 (Tetrahydroisoquinolines); A7A2802VNL (Butaclamol)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160408
[St] Status:MEDLINE
[do] DOI:10.1016/j.ijpddr.2016.02.001


  9 / 2828 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26990888
[Au] Autor:Dym O; Song W; Felder C; Roth E; Shnyrov V; Ashani Y; Xu Y; Joosten RP; Weiner L; Sussman JL; Silman I
[Ad] Endereço:Israel Structural Proteomics Center, Weizmann Institute of Science, Rehovot, 76100, Israel.
[Ti] Título:The impact of crystallization conditions on structure-based drug design: A case study on the methylene blue/acetylcholinesterase complex.
[So] Source:Protein Sci;25(6):1096-114, 2016 Jun.
[Is] ISSN:1469-896X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Structure-based drug design utilizes apoprotein or complex structures retrieved from the PDB. >57% of crystallographic PDB entries were obtained with polyethylene glycols (PEGs) as precipitant and/or as cryoprotectant, but <6% of these report presence of individual ethyleneglycol oligomers. We report a case in which ethyleneglycol oligomers' presence in a crystal structure markedly affected the bound ligand's position. Specifically, we compared the positions of methylene blue and decamethonium in acetylcholinesterase complexes obtained using isomorphous crystals precipitated with PEG200 or ammonium sulfate. The ligands' positions within the active-site gorge in complexes obtained using PEG200 are influenced by presence of ethyleneglycol oligomers in both cases bound to W84 at the gorge's bottom, preventing interaction of the ligand's proximal quaternary group with its indole. Consequently, both ligands are ∼3.0Å further up the gorge than in complexes obtained using crystals precipitated with ammonium sulfate, in which the quaternary groups make direct π-cation interactions with the indole. These findings have implications for structure-based drug design, since data for ligand-protein complexes with polyethylene glycol as precipitant may not reflect the ligand's position in its absence, and could result in selecting incorrect drug discovery leads. Docking methylene blue into the structure obtained with PEG200, but omitting the ethyleneglycols, yields results agreeing poorly with the crystal structure; excellent agreement is obtained if they are included. Many proteins display features in which precipitants might lodge. It will be important to investigate presence of precipitants in published crystal structures, and whether it has resulted in misinterpreting electron density maps, adversely affecting drug design.
[Mh] Termos MeSH primário: Acetilcolinesterase/química
Desenho de Drogas
Proteínas de Peixes/química
Azul de Metileno/química
Simulação de Acoplamento Molecular
Torpedo
[Mh] Termos MeSH secundário: Animais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fish Proteins); EC 3.1.1.7 (Acetylcholinesterase); T42P99266K (Methylene Blue)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170605
[Lr] Data última revisão:
170605
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160319
[St] Status:MEDLINE
[do] DOI:10.1002/pro.2923


  10 / 2828 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26976945
[Au] Autor:Hamouda AK; Deba F; Wang ZJ; Cohen JB
[Ad] Endereço:Department of Pharmaceutical Sciences, Rangel College of Pharmacy, Texas A&M Health Sciences Center, Kingsville, Texas (A.K.H., F.D., Z.-J.W.); and Department of Neurobiology, Harvard Medical School, Boston, Massachusetts (A.K.H., J.B.C.) hamouda@tamhsc.edu.
[Ti] Título:Photolabeling a Nicotinic Acetylcholine Receptor (nAChR) with an (α4)3(ß2)2 nAChR-Selective Positive Allosteric Modulator.
[So] Source:Mol Pharmacol;89(5):575-84, 2016 May.
[Is] ISSN:1521-0111
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Positive allosteric modulators (PAMs) of nicotinic acetylcholine (ACh) receptors (nAChRs) have potential clinical applications in the treatment of nicotine dependence and many neuropsychiatric conditions associated with decreased brain cholinergic activity, and 3-(2-chlorophenyl)-5-(5-methyl-1-(piperidin-4-yl)-1H-pyrrazol-4-yl)isoxazole (CMPI) has been identified as a PAM selective for neuronal nAChRs containing theα4 subunit. In this report, we compare CMPI interactions with low-sensitivity (α4)3(ß2)2 and high-sensitivity (α4)2(ß2)3 nAChRs, and with muscle-type nAChRs. In addition, we use the intrinsic reactivity of [(3)H]CMPI upon photolysis at 312 nm to identify its binding sites inTorpedonAChRs. Recording fromXenopusoocytes, we found that CMPI potentiated maximally the responses of (α4)3(ß2)2nAChR to 10µM ACh (EC10) by 400% and with anEC50of ∼1µM. CMPI produced a left shift of the ACh concentration-response curve without altering ACh efficacy. In contrast, CMPI inhibited (∼35% at 10µM) ACh responses of (α4)2(ß2)3nAChRs and fully inhibited human muscle andTorpedonAChRs with IC50values of ∼0.5µM. Upon irradiation at 312 nm, [(3)H]CMPI photoincorporated into eachTorpedo[(α1)2ß1γδ] nAChR subunit. Sequencing of peptide fragments isolated from [(3)H]CMPI-photolabeled nAChR subunits established photolabeling of amino acids contributing to the ACh binding sites (αTyr(190),αTyr(198),γTrp(55),γTyr(111),γTyr(117),δTrp(57)) that was fully inhibitable by agonist and lower-efficiency, state-dependent [(3)H]CMPI photolabeling within the ion channel. Our results establish that CMPI is a potent potentiator of nAChRs containing anα4:α4 subunit interface, and that its intrinsic photoreactivy makes it of potential use to identify its binding sites in the (α4)3(ß2)2nAChR.
[Mh] Termos MeSH primário: Modelos Moleculares
Proteínas Musculares/metabolismo
Proteínas do Tecido Nervoso/metabolismo
Agonistas Nicotínicos/farmacologia
Antagonistas Nicotínicos/farmacologia
Receptores Nicotínicos/metabolismo
[Mh] Termos MeSH secundário: Regulação Alostérica/efeitos dos fármacos
Animais
Sítios de Ligação
Seres Humanos
Isoxazóis/farmacologia
Cinética
Proteínas Musculares/agonistas
Proteínas Musculares/antagonistas & inibidores
Proteínas Musculares/genética
Proteínas do Tecido Nervoso/agonistas
Proteínas do Tecido Nervoso/antagonistas & inibidores
Proteínas do Tecido Nervoso/genética
Oócitos/efeitos dos fármacos
Oócitos/metabolismo
Técnicas de Patch-Clamp
Fotólise
Conformação Proteica
Isoformas de Proteínas/agonistas
Isoformas de Proteínas/antagonistas & inibidores
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
Subunidades Proteicas/agonistas
Subunidades Proteicas/antagonistas & inibidores
Subunidades Proteicas/genética
Subunidades Proteicas/metabolismo
Pirazóis/farmacologia
Ensaio Radioligante
Receptores Nicotínicos/química
Receptores Nicotínicos/genética
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Torpedo
Xenopus laevis
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (3-(2-chlorophenyl)-5-(5-methyl-1-(piperidin-4-yl)-1H-pyrazol-4-yl)isoxazole); 0 (Isoxazoles); 0 (Muscle Proteins); 0 (Nerve Tissue Proteins); 0 (Nicotinic Agonists); 0 (Nicotinic Antagonists); 0 (Protein Isoforms); 0 (Protein Subunits); 0 (Pyrazoles); 0 (Receptors, Nicotinic); 0 (Recombinant Proteins)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:170501
[Lr] Data última revisão:
170501
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160316
[St] Status:MEDLINE
[do] DOI:10.1124/mol.116.103341



página 1 de 283 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde