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Pesquisa : G02.111.679 [Categoria DeCS]
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  1 / 247439 MEDLINE  
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[PMID]:29444082
[Au] Autor:Khan MI; Su YK; Zou J; Yang LW; Chou RH; Yu C
[Ad] Endereço:National Tsing Hua University, Chemistry Department, Hsinchu, Taiwan.
[Ti] Título:S100B as an antagonist to block the interaction between S100A1 and the RAGE V domain.
[So] Source:PLoS One;13(2):e0190545, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ca2+-binding human S100A1 protein is a type of S100 protein. S100A1 is a significant mediator during inflammation when Ca2+ binds to its EF-hand motifs. Receptors for advanced glycation end products (RAGE) correspond to 5 domains: the cytoplasmic, transmembrane, C2, C1, and V domains. The V domain of RAGE is one of the most important target proteins for S100A1. It binds to the hydrophobic surface and triggers signaling transduction cascades that induce cell growth, cell proliferation, and tumorigenesis. We used nuclear magnetic resonance (NMR) spectroscopy to characterize the interaction between S100A1 and the RAGE V domain. We found that S100B could interact with S100A1 via NMR 1H-15N HSQC titrations. We used the HADDOCK program to generate the following two binary complexes based on the NMR titration results: S100A1-RAGE V domain and S100A1-S100B. After overlapping these two complex structures, we found that S100B plays a crucial role in blocking the interaction site between RAGE V domain and S100A1. A cell proliferation assay WST-1 also supported our results. This report could potentially be useful for new protein development for cancer treatment.
[Mh] Termos MeSH primário: Antígenos de Neoplasias/metabolismo
Proteínas Quinases Ativadas por Mitógeno/metabolismo
Subunidade beta da Proteína Ligante de Cálcio S100/fisiologia
Proteínas S100/metabolismo
[Mh] Termos MeSH secundário: Cálcio/metabolismo
Seres Humanos
Interações Hidrofóbicas e Hidrofílicas
Ressonância Magnética Nuclear Biomolecular
Ligação Proteica
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, Neoplasm); 0 (S100 Calcium Binding Protein beta Subunit); 0 (S100 Proteins); 0 (S100A1 protein); 0 (S100B protein, human); EC 2.7.11.22 (MOK protein, human); EC 2.7.11.24 (Mitogen-Activated Protein Kinases); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190545


  2 / 247439 MEDLINE  
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[PMID]:29378242
[Au] Autor:Wang X; Xue M; Zhao M; He F; Li C; Li X
[Ad] Endereço:Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
[Ti] Título:Identification of a novel mutation (Ala66Thr) of SRY gene causes XY pure gonadal dysgenesis by affecting DNA binding activity and nuclear import.
[So] Source:Gene;651:143-151, 2018 Apr 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Sex-determining region of the Y chromosome (SRY) gene plays a crucial role in male sexual differentiation and development. Several mutations in the SRY gene have been reported in the high mobility group (HMG) box domain and can cause gonadal dysgenesis symptoms. In this study, we report that a novel missense mutation in the SRY gene, a G to A transition within the HMG box, causes the Ala66Thr amino acid substitution in a female patient presenting 46,XY karyotype with pure gonadal dysgenesis. The G to A base transition was not found in the SRY sequence after the screening of 100 normal males. Furthermore, Ala66Thr mutation drastically reduced the binding capacity of SRY to DNA sequences, whereas wild-type SRY protein showed the normal binding capacity to DNA sequences in vitro. We also found that the mutant SRY protein was partly localized in cytoplasm, whereas wild-type SRY protein was strictly localized in cell nucleus. In addition, we analyzed the three-dimensional structure of SRY protein by homology modeling methods. In conclusion, we identified a novel SRY mutation in a 46,XY female patient with pure gonadal dysgenesis, demonstrating the importance of the Ala66Thr mutation in DNA binding activity and nuclear transport.
[Mh] Termos MeSH primário: Disgenesia Gonadal 46 XY/genética
Mutação de Sentido Incorreto
Proteína da Região Y Determinante do Sexo/genética
[Mh] Termos MeSH secundário: Transporte Ativo do Núcleo Celular
Adolescente
Adulto
Alanina
DNA/metabolismo
Feminino
Células HEK293
Seres Humanos
Cariotipagem
Masculino
Ligação Proteica
Conformação Proteica
Análise de Sequência de DNA
Proteína da Região Y Determinante do Sexo/química
Proteína da Região Y Determinante do Sexo/metabolismo
Treonina
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Sex-Determining Region Y Protein); 2ZD004190S (Threonine); 9007-49-2 (DNA); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180130
[St] Status:MEDLINE


  3 / 247439 MEDLINE  
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[PMID]:29366480
[Au] Autor:Zhang N; Zhang Y; Zhao S; Sun Y
[Ad] Endereço:Department of Cardiology, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, Liaoning 110001, PR China.
[Ti] Título:Septin4 as a novel binding partner of PARP1 contributes to oxidative stress induced human umbilical vein endothelial cells injure.
[So] Source:Biochem Biophys Res Commun;496(2):621-627, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Oxidative stress induced vascular endothelial cell injure is one of the key and initial event in the development of atherosclerosis. Septin4, as a member of GTP binding protein family, is widely expressed in the eukaryotic cells and considered to be an essential component of the cytoskeleton which is involved in many important physiological processes. However, whether Septin4 is involved in cardiovascular diseases, such as oxidative stress inducted endothelial cell injury still unclear. PARP1 as a DNA repair enzyme can be activated by identifying DNA damaged fragments, which consumes high levels of energy and leads to vascular endothelial cell apoptosis. Here, our results first found that Septin4 is involved in oxidative stress induced endothelial cell ROS production and apoptosis through knock-down and over-expression Septin4 approaches. Furthermore, to explore how Septin4 is involved in oxidative stress induced endothelial cells injure, we first identified that Septin4 is a novel PARP1 interacting protein and the interaction is enhanced under oxidative stress. In conclusions, our founding indicates that Septin4 is a novel essential factor involved in oxidative stress induced vascular endothelial cell injury by interacting with apoptosis-related protein PARP1.
[Mh] Termos MeSH primário: Células Endoteliais/metabolismo
Estresse Oxidativo
Poli(ADP-Ribose) Polimerase-1/metabolismo
Mapas de Interação de Proteínas
Septinas/metabolismo
[Mh] Termos MeSH secundário: Apoptose
Células Endoteliais/citologia
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Ligação Proteica
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Reactive Oxygen Species); EC 2.4.2.30 (PARP1 protein, human); EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1); EC 3.6.1.- (SEPT4 protein, human); EC 3.6.1.- (Septins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180126
[St] Status:MEDLINE


  4 / 247439 MEDLINE  
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[PMID]:29339159
[Au] Autor:Popinako A; Antonov M; Dibrova D; Chemeris A; Sokolova OS
[Ad] Endereço:A.N. Bach Institute of Biochemistry, Research Center of Biotechnology of RAS, 33 Leninsky Ave, bld. 2, Moscow, 119071, Russia.
[Ti] Título:Analysis of the interactions between GMF and Arp2/3 complex in two binding sites by molecular dynamics simulation.
[So] Source:Biochem Biophys Res Commun;496(2):529-535, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The Arp2/3 complex plays a key role in nucleating actin filaments branching. The glia maturation factor (GMF) competes with activators for interacting with the Arp2/3 complex and initiates the debranching of actin filaments. In this study, we performed a comparative analysis of interactions between GMF and the Arp2/3 complex and identified new amino acid residues involved in GMF binding to the Arp2/3 complex at two separate sites, revealed by X-ray and single particle EM techniques. Using molecular dynamics simulations we demonstrated the quantitative and qualitative changes in hydrogen bonds upon binding with GMF. We identified the specific amino acid residues in GMF and Arp2/3 complex that stabilize the interactions and estimated the mean force profile for the GMF using umbrella sampling. Phylogenetic and structural analyses of the recently defined GMF binding site on the Arp3 subunit indicate a new mechanism for Arp2/3 complex inactivation that involves interactions between the Arp2/3 complex and GMF at two binding sites.
[Mh] Termos MeSH primário: Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo
Fator de Maturação da Glia/metabolismo
[Mh] Termos MeSH secundário: Complexo 2-3 de Proteínas Relacionadas à Actina/química
Animais
Sítios de Ligação
Bovinos
Cristalografia por Raios X
Fator de Maturação da Glia/química
Camundongos
Simulação de Dinâmica Molecular
Ligação Proteica
Mapas de Interação de Proteínas
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Actin-Related Protein 2-3 Complex); 0 (Glia Maturation Factor)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE


  5 / 247439 MEDLINE  
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[PMID]:29331375
[Au] Autor:Ma L; Wang Q; Yuan M; Zou T; Yin P; Wang S
[Ad] Endereço:National Key Laboratory of Crop Genetic Improvement, National Center of Plant Gene Research (Wuhan), Huazhong Agricultural University, Wuhan 430070, China.
[Ti] Título:Xanthomonas TAL effectors hijack host basal transcription factor IIA α and γ subunits for invasion.
[So] Source:Biochem Biophys Res Commun;496(2):608-613, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The Xanthomonas genus includes Gram-negative plant-pathogenic bacteria, which infect a broad range of crops and wild plant species, cause symptoms with leaf blights, streaks, spots, stripes, necrosis, wilt, cankers and gummosis on leaves, stems and fruits in a wide variety of plants via injecting their effector proteins into the host cell during infection. Among these virulent effectors, transcription activator-like effectors (TALEs) interact with the γ subunit of host transcription factor IIA (TFIIAγ) to activate the transcription of host disease susceptibility genes. Functional TFIIA is a ternary complex comprising α, ß and γ subunits. However, whether TALEs recruit TFIIAα, TFIIAß, or both remains unknown. The underlying molecular mechanisms by which TALEs mediate host susceptibility gene activation require full elucidation. Here, we show that TALEs interact with the α+γ binary subcomplex but not the α+ß+γ ternary complex of rice TFIIA (holo-OsTFIIA). The transcription factor binding (TFB) regions of TALEs, which are highly conserved in Xanthomonas species, have a dominant role in these interactions. Furthermore, the interaction between TALEs and the α+γ complex exhibits robust DNA binding activity in vitro. These results collectively demonstrate that TALE-carrying pathogens hijack the host basal transcription factors TFIIAα and TFIIAγ, but not TFIIAß, to enhance host susceptibility during pathogen infection. The uncovered mechanism widens new insights on host-microbe interaction and provide an applicable strategy to breed high-resistance crop varieties.
[Mh] Termos MeSH primário: Interações Hospedeiro-Patógeno
Oryza/microbiologia
Doenças das Plantas/microbiologia
Proteínas de Plantas/metabolismo
Efetores Semelhantes a Ativadores de Transcrição/metabolismo
Fator de Transcrição TFIIA/metabolismo
Xanthomonas/fisiologia
[Mh] Termos MeSH secundário: Resistência à Doença
Regulação da Expressão Gênica de Plantas
Genes de Plantas
Oryza/genética
Oryza/metabolismo
Doenças das Plantas/genética
Ligação Proteica
Subunidades Proteicas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Plant Proteins); 0 (Protein Subunits); 0 (Transcription Activator-Like Effectors); 0 (Transcription Factor TFIIA)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180115
[St] Status:MEDLINE


  6 / 247439 MEDLINE  
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[PMID]:29288668
[Au] Autor:Groves MR; Schroer CFE; Middleton AJ; Lunev S; Danda N; Ali AM; Marrink SJ; Williams C
[Ad] Endereço:Department of Drug Design, Groningen Research Institute of Pharmacy, University of Groningen, 9713AV, The Netherlands.
[Ti] Título:Structural insights into K48-linked ubiquitin chain formation by the Pex4p-Pex22p complex.
[So] Source:Biochem Biophys Res Commun;496(2):562-567, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pex4p is a peroxisomal E2 involved in ubiquitinating the conserved cysteine residue of the cycling receptor protein Pex5p. Previously, we demonstrated that Pex4p from the yeast Saccharomyces cerevisiae binds directly to the peroxisomal membrane protein Pex22p and that this interaction is vital for receptor ubiquitination. In addition, Pex22p binding allows Pex4p to specifically produce lysine 48 linked ubiquitin chains in vitro through an unknown mechanism. This activity is likely to play a role in targeting peroxisomal proteins for proteasomal degradation. Here we present the crystal structures of Pex4p alone and in complex with Pex22p from the yeast Hansenula polymorpha. Comparison of the two structures demonstrates significant differences to the active site of Pex4p upon Pex22p binding while molecular dynamics simulations suggest that Pex22p binding facilitates active site remodelling of Pex4p through an allosteric mechanism. Taken together, our data provide insights into how Pex22p binding allows Pex4p to build K48-linked Ub chains.
[Mh] Termos MeSH primário: Proteínas Fúngicas/metabolismo
Peroxinas/metabolismo
Pichia/metabolismo
[Mh] Termos MeSH secundário: Domínio Catalítico
Cristalografia por Raios X
Proteínas Fúngicas/química
Modelos Moleculares
Peroxinas/química
Pichia/química
Ligação Proteica
Conformação Proteica
Ubiquitinação
Ubiquitinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Fungal Proteins); 0 (Peroxins); 0 (Ubiquitins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171231
[St] Status:MEDLINE


  7 / 247439 MEDLINE  
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[PMID]:29208012
[Au] Autor:Pereira A; Paro R
[Ad] Endereço:Department of Biosystems Science and Engineering, ETH Zurich, 4058, Basel, Switzerland.
[Ti] Título:Pho dynamically interacts with Spt5 to facilitate transcriptional switches at the hsp70 locus.
[So] Source:Epigenetics Chromatin;10(1):57, 2017 12 06.
[Is] ISSN:1756-8935
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Numerous target genes of the Polycomb group (PcG) are transiently activated by a stimulus and subsequently repressed. However, mechanisms by which PcG proteins regulate such target genes remain elusive. RESULTS: We employed the heat shock-responsive hsp70 locus in Drosophila to study the chromatin dynamics of PRC1 and its interplay with known regulators of the locus before, during and after heat shock. We detected mutually exclusive binding patterns for HSF and PRC1 at the hsp70 locus. We found that Pleiohomeotic (Pho), a DNA-binding PcG member, dynamically interacts with Spt5, an elongation factor. The dynamic interaction switch between Pho and Spt5 is triggered by the recruitment of HSF to chromatin. Mutation in the protein-protein interaction domain (REPO domain) of Pho interferes with the dynamics of its interaction with Spt5. The transcriptional kinetics of the heat shock response is negatively affected by a mutation in the REPO domain of Pho. CONCLUSIONS: We propose that a dynamic interaction switch between PcG proteins and an elongation factor enables stress-inducible genes to efficiently switch between ON/OFF states in the presence/absence of the activating stimulus.
[Mh] Termos MeSH primário: Proteínas Cromossômicas não Histona/metabolismo
Proteínas de Drosophila/metabolismo
Proteínas de Choque Térmico HSP70/genética
Proteínas do Grupo Polycomb/metabolismo
Fatores de Elongação da Transcrição/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Linhagem Celular
Cromatina/metabolismo
Proteínas de Drosophila/química
Drosophila melanogaster
Resposta ao Choque Térmico
Proteínas do Grupo Polycomb/química
Ligação Proteica
Homologia de Sequência de Aminoácidos
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Chromatin); 0 (Chromosomal Proteins, Non-Histone); 0 (Drosophila Proteins); 0 (HSP70 Heat-Shock Proteins); 0 (Polycomb-Group Proteins); 0 (Transcriptional Elongation Factors); 0 (pho protein, Drosophila); 138673-72-0 (SPT5 transcriptional elongation factor)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180310
[Lr] Data última revisão:
180310
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171207
[St] Status:MEDLINE
[do] DOI:10.1186/s13072-017-0166-9


  8 / 247439 MEDLINE  
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[PMID]:28466911
[Au] Autor:Scheller JS; Irvine GW; Wong DL; Hartwig A; Stillman MJ
[Ad] Endereço:Department of Chemistry, The University of Western Ontario, London, Ontario, N6A 5B7, Canada. martin.stillman@uwo.ca.
[Ti] Título:Stepwise copper(i) binding to metallothionein: a mixed cooperative and non-cooperative mechanism for all 20 copper ions.
[So] Source:Metallomics;9(5):447-462, 2017 May 24.
[Is] ISSN:1756-591X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Copper is a ubiquitous trace metal of vital importance in that it serves as a cofactor in many metalloenzymes. Excess copper becomes harmful if not sequestered appropriately in the cell. As a metal ion chaperone, metallothionein (MT) has been proposed as a key player in zinc and copper homeostasis within the cell. The underlying mechanisms by which MT sequesters and transfers copper ions, and subsequently achieves its proposed biological function remain unknown. Using a combination of electrospray ionization mass spectrometry (ESI-MS), circular dichroism (CD), and emission spectroscopy, we report that the Cu(i) to human apo-MT1a binding mechanism is highly pH-dependent. The 20 relative K -values for the binding of 1 to 20 Cu(i) to the 20 cysteines of MT were obtained from computational simulation of the experimental mass spectral results. These data identified the pH-dependent formation of three sequential but completely different Cu-S clusters, as a function of Cu(i) loading. These data provide the first overall sequence for Cu(i) binding in terms of domain specificity and transient binding site structures. Under cooperative binding at pH 7.4, a series of four clusters form: Cu S , followed by Cu S (ß), then a second Cu S (α), and finally Cu S (α) (x = up to 11). Upon further addition of Cu(i), a mixture of species is formed in a non-cooperative mechanism, saturating the 20 cysteines of MT1a. Using benzoquinone, a cysteine modifier, we were able to confirm that Cu S formed solely in the N-terminal ß-domain, as well as confirming the existence of the presumed Cu S cluster in the α-domain. Based on the results of ESI-MS and computational simulation we were able to identify Cu:MT speciation that resulted in specific emission and CD spectral properties.
[Mh] Termos MeSH primário: Cobre/metabolismo
Metalotioneína/metabolismo
[Mh] Termos MeSH secundário: Sítios de Ligação
Dicroísmo Circular
Cobre/química
Seres Humanos
Concentração de Íons de Hidrogênio
Metalotioneína/química
Modelos Moleculares
Ligação Proteica
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Espectrometria de Massas por Ionização por Electrospray
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MT1A protein, human); 0 (Recombinant Proteins); 789U1901C5 (Copper); 9038-94-2 (Metallothionein)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1039/c7mt00041c


  9 / 247439 MEDLINE  
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[PMID]:28463568
[Au] Autor:Salinas G; Gao W; Wang Y; Bonilla M; Yu L; Novikov A; Virginio VG; Ferreira HB; Vieites M; Gladyshev VN; Gambino D; Dai S
[Ad] Endereço:1 Worm Biology Lab, Institut Pasteur de Montevideo , Montevideo, Uruguay .
[Ti] Título:The Enzymatic and Structural Basis for Inhibition of Echinococcus granulosus Thioredoxin Glutathione Reductase by Gold(I).
[So] Source:Antioxid Redox Signal;27(18):1491-1504, 2017 Dec 20.
[Is] ISSN:1557-7716
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIMS: New drugs are needed to treat flatworm infections that cause severe human diseases such as schistosomiasis. The unique flatworm enzyme thioredoxin glutathione reductase (TGR), structurally different from the human enzyme, is a key drug target. Structural studies of the flatworm Echinococcus granulosus TGR, free and complexed with Au -MPO, a novel gold inhibitor, together with inhibition assays were performed. RESULTS: Au -MPO is a potent TGR inhibitor that achieves 75% inhibition at a 1:1 TGR:Au ratio and efficiently kills E. granulosus in vitro. The structures revealed salient insights: (i) unique monomer-monomer interactions, (ii) distinct binding sites for thioredoxin and the glutaredoxin (Grx) domain, (iii) a single glutathione disulfide reduction site in the Grx domain, (iv) rotation of the Grx domain toward the Sec-containing redox active site, and (v) a single gold atom bound to Cys and Cys in the Au -TGR complex. Structural modeling suggests that these residues are involved in the stabilization of the Sec-containing C-terminus. Consistently, Cys→Ser mutations in these residues decreased TGR activities. Mass spectroscopy confirmed these cysteines are the primary binding site. INNOVATION: The identification of a primary site for gold binding and the structural model provide a basis for gold compound optimization through scaffold adjustments. CONCLUSIONS: The structural study revealed that TGR functions are achieved not only through a mobile Sec-containing redox center but also by rotation of the Grx domain and distinct binding sites for Grx domain and thioredoxin. The conserved Cys and Cys residues targeted by gold assist catalysis through stabilization of the Sec-containing redox center. Antioxid. Redox Signal. 27, 1491-1504.
[Mh] Termos MeSH primário: Echinococcus granulosus/enzimologia
Complexos Multienzimáticos/química
Complexos Multienzimáticos/metabolismo
NADH NADPH Oxirredutases/química
NADH NADPH Oxirredutases/metabolismo
Compostos Organoáuricos/farmacologia
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação/efeitos dos fármacos
Cisteína/metabolismo
Echinococcus granulosus/química
Echinococcus granulosus/genética
Inibidores Enzimáticos/química
Inibidores Enzimáticos/farmacocinética
Glutarredoxinas/metabolismo
Proteínas de Helminto/química
Proteínas de Helminto/genética
Proteínas de Helminto/metabolismo
Modelos Moleculares
Complexos Multienzimáticos/genética
Mutação
NADH NADPH Oxirredutases/genética
Compostos Organoáuricos/química
Ligação Proteica
Conformação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Glutaredoxins); 0 (Helminth Proteins); 0 (Multienzyme Complexes); 0 (Organogold Compounds); EC 1.6.- (NADH, NADPH Oxidoreductases); EC 1.6.4.- (thioredoxin glutathione reductase); K848JZ4886 (Cysteine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1089/ars.2016.6816


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[PMID]:29458526
[Au] Autor:Ma J; Wei Y; Zhang L; Wang X; Yao D; Liu D; Liu W; Yu S; Yu Y; Wu Z; Yu L; Zhu Z; Cui Y
[Ad] Endereço:College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, PR China.
[Ti] Título:Identification of a novel linear B-cell epitope as a vaccine candidate in the N2N3 subdomain of Staphylococcus aureus fibronectin-binding protein A.
[So] Source:J Med Microbiol;67(3):423-431, 2018 Mar.
[Is] ISSN:1473-5644
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To explore an epitope-based vaccine against Staphylococcus aureus, we screened the epitopes in the N2N3 subdomain of fibronectin-binding protein A (FnBPA) as a surface component of S. aureus. METHODOLOGY: We expressed N2N3 proteins and prepared monoclonal antibodies (mAbs) against N2N3 by the hybridoma technique, before screening the B-cell epitopes in N2N3 using a phage-displayed random 12-mer peptide library with these mAbs against N2N3. Finally, we analysed the characters of the screened epitopes using immunofluorescence and an S. aureus infection assay. RESULTS: In this paper, we identified a linear B-cell epitope in N2N3 through screening a phage-displayed peptide library with a 3C3 mAb against the N2N3. The 3C3 mAb recognized the 159IETFNKANNRFSH171 sequence of the N2N3 subdomain. Subsequently, site-directed mutagenic analysis demonstrated that residues F162, K164, N167, R168 and F169 formed the core of 159IETFNKANNRFSH171, and this core motif was the minimal determinant of the B-cell epitope recognized by the 3C3 mAb. The epitope 159IETFNKANNRFSH171 showed high homology among different S. aureus strains. Moreover, this epitope was exposed on the surface of the S. aureus by using an enzyme-linked immunosorbent assay (ELISA) assay and an indirect immunofluorescence assay. As expected, the epitope peptide evoked a protective immune response against S. aureus infection in immunized mice. CONCLUSION: We identified a novel linear B-cell epitope, 159IETFNKANNRFSH171, in the N2N3 subdomain of S. aureus fibronectin-binding protein A that is recognized by 3C3 mAb, which will contribute to the further study of an epitope-based vaccine candidate against S. aureus.
[Mh] Termos MeSH primário: Adesinas Bacterianas/imunologia
Epitopos de Linfócito B/imunologia
Infecções Estafilocócicas/prevenção & controle
Vacinas Antiestafilocócicas/imunologia
Staphylococcus aureus/imunologia
[Mh] Termos MeSH secundário: Adesinas Bacterianas/química
Adesinas Bacterianas/genética
Animais
Anticorpos Monoclonais/imunologia
Anticorpos Monoclonais/isolamento & purificação
Ensaio de Imunoadsorção Enzimática
Mapeamento de Epitopos
Epitopos de Linfócito B/química
Epitopos de Linfócito B/genética
Imunização
Camundongos
Biblioteca de Peptídeos
Ligação Proteica
Infecções Estafilocócicas/imunologia
Staphylococcus aureus/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adhesins, Bacterial); 0 (Antibodies, Monoclonal); 0 (Epitopes, B-Lymphocyte); 0 (Peptide Library); 0 (Staphylococcal Vaccines); 0 (fibronectin-binding proteins, bacterial)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180221
[St] Status:MEDLINE
[do] DOI:10.1099/jmm.0.000633



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