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[PMID]:28535267
[Au] Autor:Charles RC; Nakajima R; Liang L; Jasinskas A; Berger A; Leung DT; Kelly M; Xu P; Kovác P; Giffen SR; Harbison JD; Chowdhury F; Khan AI; Calderwood SB; Bhuiyan TR; Harris JB; Felgner PL; Qadri F; Ryan ET
[Ad] Endereço:Division of Infectious Diseases, Massachusetts General Hospital.
[Ti] Título:Plasma and Mucosal Immunoglobulin M, Immunoglobulin A, and Immunoglobulin G Responses to the Vibrio cholerae O1 Protein Immunome in Adults With Cholera in Bangladesh.
[So] Source:J Infect Dis;216(1):125-134, 2017 Jul 01.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Cholera is a severe dehydrating illness of humans caused by toxigenic strains of Vibrio cholerae O1 or O139. Identification of immunogenic V. cholerae antigens could lead to a better understanding of protective immunity in human cholera. Methods: We probed microarrays containing 3652 V. cholerae antigens with plasma and antibody-in-lymphocyte supernatant (ALS, a surrogate marker of mucosal immune responses) from patients with severe cholera caused by V. cholerae O1 in Bangladesh and age-, sex-, and ABO-matched Bangladeshi controls. We validated a subset of identified antigens using enzyme-linked immunosorbent assay. Results: Overall, we identified 608 immunoreactive V. cholerae antigens in our screening, 59 of which had higher immunoreactivity in convalescent compared with acute-stage or healthy control samples (34 in plasma, 39 in mucosal ALS; 13 in both sample sets). Identified antigens included cholera toxin B and A subunits, V. cholerae O-specific polysaccharide and lipopolysaccharide, toxin coregulated pilus A, sialidase, hemolysin A, flagellins (FlaB, FlaC, and FlaD), phosphoenolpyruvate-protein phosphotransferase, and diaminobutyrate-2-oxoglutarate aminotransferase. Conclusions: This study is the first antibody profiling of the mucosal and systemic antibody responses to the nearly complete V. cholerae O1 protein immunome; it has identified antigens that may aid in the development of an improved cholera vaccine.
[Mh] Termos MeSH primário: Cólera/imunologia
Imunidade nas Mucosas
Imunoglobulina A/sangue
Imunoglobulina G/sangue
Imunoglobulina M/sangue
Vibrio cholerae O1/imunologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Anticorpos Antibacterianos/sangue
Formação de Anticorpos
Bangladesh/epidemiologia
Estudos de Casos e Controles
Cólera/epidemiologia
Toxina da Cólera/sangue
Feminino
Flagelina/sangue
Seres Humanos
Leucócitos Mononucleares/metabolismo
Masculino
Meia-Idade
Membrana Mucosa/imunologia
Antígenos O/sangue
Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato/sangue
Fosfotransferases (Aceptor do Grupo Nitrogenado)/sangue
Reprodutibilidade dos Testes
Vibrio cholerae O1/isolamento & purificação
Vibrio cholerae O139/isolamento & purificação
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Bacterial); 0 (Immunoglobulin A); 0 (Immunoglobulin G); 0 (Immunoglobulin M); 0 (O Antigens); 12777-81-0 (Flagellin); 9012-63-9 (Cholera Toxin); EC 2.7.1.- (Phosphoenolpyruvate Sugar Phosphotransferase System); EC 2.7.3.- (Phosphotransferases (Nitrogenous Group Acceptor)); EC 2.7.3.9 (phosphoenolpyruvate-protein phosphotransferase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171117
[Lr] Data última revisão:
171117
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170524
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix253


  2 / 184 MEDLINE  
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[PMID]:28525571
[Au] Autor:Mueller L; Bertelli C; Pillonel T; Salamin N; Greub G
[Ad] Endereço:Center for Research on Intracellular Bacteria (CRIB), Institute of Microbiology, Lausanne University Hospital, and University of Lausanne, Switzerland.
[Ti] Título:One Year Genome Evolution of Lausannevirus in Allopatric versus Sympatric Conditions.
[So] Source:Genome Biol Evol;9(6):1432-1449, 2017 Jun 01.
[Is] ISSN:1759-6653
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Amoeba-resisting microorganisms raised a great interest during the last decade. Among them, some large DNA viruses present huge genomes up to 2.5 Mb long, exceeding the size of small bacterial genomes. The rate of genome evolution in terms of mutation, deletion, and gene acquisition in these genomes is yet unknown. Given the suspected high plasticity of viral genomes, the microevolution of the 346 kb genome of Lausannevirus, a member of Megavirales, was studied. Hence, Lausannevirus was co-cultured within the amoeba Acanthamoeba castellanii over one year. Despite a low number of mutations, the virus showed a genome reduction of 3.7% after 12 months. Lausannevirus genome evolution in sympatric conditions was investigated by its co-culture with Estrella lausannensis, an obligate intracellular bacterium, in the amoeba A. castellanii during one year. Cultures were split every 3 months. Genome sequencing revealed that in these conditions both, Lausannevirus and E. lausannensis, show stable genome, presenting no major rearrangement. In fact, after one year they acquired from 2 to 7 and from 4 to 10 mutations per culture for Lausannevirus and E. lausannensis, respectively. Interestingly, different mutations in the endonuclease encoding genes of Lausannevirus were observed in different subcultures, highlighting the importance of this gene product in the replication of Lausannevirus. Conversely, mutations in E. lausannensis were mainly located in a gene encoding for a phosphoenolpyruvate-protein phosphotransferase (PtsI), implicated in sugar metabolism. Moreover, in our conditions and with our analyses we detected no horizontal gene transfer during one year of co-culture.
[Mh] Termos MeSH primário: Acanthamoeba castellanii/virologia
Evolução Molecular
Especiação Genética
Genoma Viral
Vírus Gigantes/genética
[Mh] Termos MeSH secundário: Evolução Biológica
Vírus Gigantes/classificação
Mutação
Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato/genética
Fosfotransferases (Aceptor do Grupo Nitrogenado)/genética
Filogenia
Análise de Sequência de DNA
Simpatria
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.1.- (Phosphoenolpyruvate Sugar Phosphotransferase System); EC 2.7.3.- (Phosphotransferases (Nitrogenous Group Acceptor)); EC 2.7.3.9 (phosphoenolpyruvate-protein phosphotransferase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170520
[St] Status:MEDLINE
[do] DOI:10.1093/gbe/evx074


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[PMID]:26990554
[Au] Autor:Mizrachi Nebenzahl Y; Blau K; Kushnir T; Shagan M; Portnoi M; Cohen A; Azriel S; Malka I; Adawi A; Kafka D; Dotan S; Guterman G; Troib S; Fishilevich T; Gershoni JM; Braiman A; Mitchell AM; Mitchell TJ; Porat N; Goliand I; Chalifa Caspi V; Swiatlo E; Tal M; Ellis R; Elia N; Dagan R
[Ad] Endereço:Pediatric Infectious Disease Unit, Soroka University Medical Center, Beer Sheva, Israel.
[Ti] Título:Streptococcus pneumoniae Cell-Wall-Localized Phosphoenolpyruvate Protein Phosphotransferase Can Function as an Adhesin: Identification of Its Host Target Molecules and Evaluation of Its Potential as a Vaccine.
[So] Source:PLoS One;11(3):e0150320, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In Streptococcus pneumonia, phosphoenolpyruvate protein phosphotransferase (PtsA) is an intracellular protein of the monosaccharide phosphotransferase systems. Biochemical and immunostaining methods were applied to show that PtsA also localizes to the bacterial cell-wall. Thus, it was suspected that PtsA has functions other than its main cytoplasmic enzymatic role. Indeed, recombinant PtsA and anti-rPtsA antiserum were shown to inhibit adhesion of S. pneumoniae to cultured human lung adenocarcinoma A549 cells. Screening of a combinatorial peptide library expressed in a filamentous phage with rPtsA identified epitopes that were capable of inhibiting S. pneumoniae adhesion to A549 cells. The insert peptides in the phages were sequenced, and homologous sequences were found in human BMPER, multimerin1, protocadherin19, integrinß4, epsin1 and collagen type VIIα1 proteins, all of which can be found in A549 cells except the latter. Six peptides, synthesized according to the homologous sequences in the human proteins, specifically bound rPtsA in the micromolar range and significantly inhibited pneumococcal adhesion in vitro to lung- and tracheal-derived cell lines. In addition, the tested peptides inhibited lung colonization after intranasal inoculation of mice with S. pneumoniae. Immunization with rPtsA protected the mice against a sublethal intranasal and a lethal intravenous pneumococcal challenge. In addition, mouse anti rPtsA antiserum reduced bacterial virulence in the intravenous inoculation mouse model. These findings showed that the surface-localized PtsA functions as an adhesin, PtsA binding peptides derived from its putative target molecules can be considered for future development of therapeutics, and rPtsA should be regarded as a candidate for vaccine development.
[Mh] Termos MeSH primário: Parede Celular/enzimologia
Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato/metabolismo
Fosfotransferases (Aceptor do Grupo Nitrogenado)/metabolismo
Vacinas Pneumocócicas/imunologia
Streptococcus pneumoniae/enzimologia
[Mh] Termos MeSH secundário: Adesinas Bacterianas/fisiologia
Linhagem Celular Tumoral
Pré-Escolar
Citometria de Fluxo
Seres Humanos
Streptococcus pneumoniae/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adhesins, Bacterial); 0 (Pneumococcal Vaccines); EC 2.7.1.- (Phosphoenolpyruvate Sugar Phosphotransferase System); EC 2.7.3.- (Phosphotransferases (Nitrogenous Group Acceptor)); EC 2.7.3.9 (phosphoenolpyruvate-protein phosphotransferase)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160319
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0150320


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[PMID]:26740364
[Au] Autor:Saijuntha W; Tantrawatpan C; Jarilla BR; Agatsuma T; Andrews RH; Petney TN
[Ad] Endereço:Walai Rukhavej Botanical Research Institute (WRBRI), Mahasarakham University, Maha Sarakham 44150, Thailand.
[Ti] Título:Intron sequence of the taurocyamine kinase gene as a marker to investigate genetic variation of Paragonimus species in Japan and the origins of triploidy in P. westermani.
[So] Source:Trans R Soc Trop Med Hyg;110(1):67-73, 2016 Jan.
[Is] ISSN:1878-3503
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Paragonimiasis is a foodborne parasitic infection caused by lung flukes of the genus Paragonimus. Several species of Paragonimus are endemic in Japan: P. westermani (diploid and triploid) P. miyazakii, P. ohirai and P. iloktsuenensis. The taxonomic status and genetic variability of these lung flukes remains poorly understood. METHODS: The second intron of domain 1 of the taurocyamine kinase gene (TKD1int2) region was used to explore genetic variation and differentiation of diploid and triploid P. westermani, as well as P. miyazakii, P. ohirai and P. iloktsuenensis originating from Japan. RESULTS: We found high levels of intraspecific variation in P. westermani, but only low levels of variation within the other species studied. Haplotype network and phylogenetic tree analyses demonstrated the sister-group relationship of P. ohirai and P. iloktsuenensis and the phylogenetically distant relationship of P. westermani with the other species. All individuals except for triploid P. westermani were homozygous. Each triploid contained at least one allele similar to that seen in most diploids from Chiba and one allele resembling that seen in diploids from Oita. One triploid contained three different sequences. CONCLUSIONS: Our findings suggested that the TKD1int2 region is a suitable marker for use in studying the genetic variation and phylogenetics of Paragonimus species, as well as providing clues to the origins of triploidy in P. westermani.
[Mh] Termos MeSH primário: DNA de Helmintos/genética
Variação Genética/genética
Íntrons/genética
Paragonimíase/parasitologia
Paragonimus/genética
Fosfotransferases (Aceptor do Grupo Nitrogenado)/genética
Triploidia
[Mh] Termos MeSH secundário: Animais
Marcadores Genéticos
Japão
Paragonimus westermani/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Helminth); 0 (Genetic Markers); EC 2.7.3.- (Phosphotransferases (Nitrogenous Group Acceptor)); EC 2.7.3.4 (taurocyamine kinase)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160108
[St] Status:MEDLINE
[do] DOI:10.1093/trstmh/trv109


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[PMID]:26305976
[Au] Autor:Venditti V; Schwieters CD; Grishaev A; Clore GM
[Ad] Endereço:Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520; Department of Chemistry, Iowa State University, Ames, IA 50011;
[Ti] Título:Dynamic equilibrium between closed and partially closed states of the bacterial Enzyme I unveiled by solution NMR and X-ray scattering.
[So] Source:Proc Natl Acad Sci U S A;112(37):11565-70, 2015 Sep 15.
[Is] ISSN:1091-6490
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Enzyme I (EI) is the first component in the bacterial phosphotransferase system, a signal transduction pathway in which phosphoryl transfer through a series of bimolecular protein-protein interactions is coupled to sugar transport across the membrane. EI is a multidomain, 128-kDa homodimer that has been shown to exist in two conformational states related to one another by two large (50-90°) rigid body domain reorientations. The open conformation of apo EI allows phosphoryl transfer from His189 located in the N-terminal domain α/ß (EIN(α/ß)) subdomain to the downstream protein partner bound to the EIN(α) subdomain. The closed conformation, observed in a trapped phosphoryl transfer intermediate, brings the EIN(α/ß) subdomain into close proximity to the C-terminal dimerization domain (EIC), thereby permitting in-line phosphoryl transfer from phosphoenolpyruvate (PEP) bound to EIC to His189. Here, we investigate the solution conformation of a complex of an active site mutant of EI (H189A) with PEP. Simulated annealing refinement driven simultaneously by solution small angle X-ray scattering and NMR residual dipolar coupling data demonstrates unambiguously that the EI(H189A)-PEP complex exists in a dynamic equilibrium between two approximately equally populated conformational states, one corresponding to the closed structure and the other to a partially closed species. The latter likely represents an intermediate in the open-to-closed transition.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
Escherichia coli/enzimologia
Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato/química
Fosfotransferases (Aceptor do Grupo Nitrogenado)/química
[Mh] Termos MeSH secundário: Algoritmos
Domínio Catalítico
Ligantes
Espectroscopia de Ressonância Magnética
Simulação de Dinâmica Molecular
Mutação
Nitrogênio/química
Fosforilação
Ligação Proteica
Multimerização Proteica
Estrutura Secundária de Proteína
Espalhamento de Radiação
Transdução de Sinais
Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, N.I.H., INTRAMURAL
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Ligands); EC 2.7.1.- (Phosphoenolpyruvate Sugar Phosphotransferase System); EC 2.7.3.- (Phosphotransferases (Nitrogenous Group Acceptor)); EC 2.7.3.9 (phosphoenolpyruvate-protein phosphotransferase); N762921K75 (Nitrogen)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150826
[St] Status:MEDLINE
[do] DOI:10.1073/pnas.1515366112


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[PMID]:25900685
[Au] Autor:Ryabov Y
[Ad] Endereço:BC Portal Inc., 260 Congressional Ln. #204, Rockville, Maryland, 20852.
[Ti] Título:Coupling between overall rotational diffusion and domain motions in proteins and its effect on dielectric spectra.
[So] Source:Proteins;83(9):1571-81, 2015 Sep.
[Is] ISSN:1097-0134
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this work, we formulate a closed-form solution of the model of a semirigid molecule for the case of fluctuating and reorienting molecular electric dipole moment. We illustrate with numeric calculations the impact of protein domain motions on dielectric spectra using the example of the 128 kDa protein dimer of Enzyme I. We demonstrate that the most drastic effect occurs for situations when the characteristic time of protein domain dynamics is comparable to the time of overall molecular rotational diffusion. We suggest that protein domain motions could be a possible explanation for the high-frequency contribution that accompanies the major relaxation dispersion peak in the dielectric spectra of protein aqueous solutions. We propose that the presented computational methodology could be used for the simultaneous analysis of dielectric spectroscopy and nuclear magnetic resonance data. Proteins 2015; 83:1571-1581. © 2015 Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Algoritmos
Biologia Computacional/métodos
Espectroscopia Dielétrica/métodos
Estrutura Terciária de Proteína
Proteínas/química
[Mh] Termos MeSH secundário: Difusão
Espectroscopia de Ressonância Magnética/métodos
Modelos Moleculares
Movimento (Física)
Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato/química
Fosfotransferases (Aceptor do Grupo Nitrogenado)/química
Multimerização Proteica
Reprodutibilidade dos Testes
Rotação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Proteins); EC 2.7.1.- (Phosphoenolpyruvate Sugar Phosphotransferase System); EC 2.7.3.- (Phosphotransferases (Nitrogenous Group Acceptor)); EC 2.7.3.9 (phosphoenolpyruvate-protein phosphotransferase)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:150821
[Lr] Data última revisão:
150821
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150423
[St] Status:MEDLINE
[do] DOI:10.1002/prot.24814


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[PMID]:25837252
[Au] Autor:Merceron R; Awama AM; Montserret R; Marcillat O; Gouet P
[Ad] Endereço:From the Institut de Biologie et Chimie des Protéines, BMSSI-IBCP, UMR 5086 CNRS Université Lyon 1, 7, Passage du Vercors, 69367 Lyon Cedex 07, France and.
[Ti] Título:The substrate-free and -bound crystal structures of the duplicated taurocyamine kinase from the human parasite Schistosoma mansoni.
[So] Source:J Biol Chem;290(20):12951-63, 2015 May 15.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The taurocyamine kinase from the blood fluke Schistosoma mansoni (SmTK) belongs to the phosphagen kinase (PK) family and catalyzes the reversible Mg(2+)-dependent transfer of a phosphoryl group between ATP and taurocyamine. SmTK is derived from gene duplication, as are all known trematode TKs. Our crystallographic study of SmTK reveals the first atomic structure of both a TK and a PK with a bilobal structure. The two unliganded lobes present a canonical open conformation and interact via their respective C- and N-terminal domains at a helix-mediated interface. This spatial arrangement differs from that observed in true dimeric PKs, in which both N-terminal domains make contact. Our structures of SmTK complexed with taurocyamine or l-arginine compounds explain the mechanism by which an arginine residue of the phosphagen specificity loop is crucial for substrate specificity. An SmTK crystal was soaked with the dead end transition state analog (TSA) components taurocyamine-NO3 (2-)-MgADP. One SmTK monomer was observed with two bound TSAs and an asymmetric conformation, with the first lobe semiclosed and the second closed. However, isothermal titration calorimetry and enzyme kinetics experiments showed that the two lobes function independently. A small angle x-ray scattering model of SmTK-TSA in solution with two closed active sites was generated.
[Mh] Termos MeSH primário: Proteínas de Helminto/química
Modelos Moleculares
Fosfotransferases (Aceptor do Grupo Nitrogenado)/química
Schistosoma mansoni/enzimologia
Taurina/análogos & derivados
[Mh] Termos MeSH secundário: Animais
Cristalografia por Raios X
Seres Humanos
Estrutura Secundária de Proteína
Estrutura Terciária de Proteína
Taurina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Helminth Proteins); 1EQV5MLY3D (Taurine); 543-18-0 (taurocyamine); EC 2.7.3.- (Phosphotransferases (Nitrogenous Group Acceptor)); EC 2.7.3.4 (taurocyamine kinase)
[Em] Mês de entrada:1507
[Cu] Atualização por classe:160516
[Lr] Data última revisão:
160516
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150404
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M114.628909


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[PMID]:25581904
[Au] Autor:Venditti V; Tugarinov V; Schwieters CD; Grishaev A; Clore GM
[Ad] Endereço:Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA.
[Ti] Título:Large interdomain rearrangement triggered by suppression of micro- to millisecond dynamics in bacterial Enzyme I.
[So] Source:Nat Commun;6:5960, 2015 Jan 12.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Enzyme I (EI), the first component of the bacterial phosphotransfer signal transduction system, undergoes one of the largest substrate-induced interdomain rearrangements documented to date. Here we characterize the perturbations generated by two small molecules, the natural substrate phosphoenolpyruvate and the inhibitor α-ketoglutarate, on the structure and dynamics of EI using NMR, small-angle X-ray scattering and biochemical techniques. The results indicate unambiguously that the open-to-closed conformational switch of EI is triggered by complete suppression of micro- to millisecond dynamics within the C-terminal domain of EI. Indeed, we show that a ligand-induced transition from a dynamic to a more rigid conformational state of the C-terminal domain stabilizes the interface between the N- and C-terminal domains observed in the structure of the closed state, thereby promoting the resulting conformational switch and autophosphorylation of EI. The mechanisms described here may be common to several other multidomain proteins and allosteric systems.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
Enzimas/química
Escherichia coli/enzimologia
Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato/química
Fosfotransferases (Aceptor do Grupo Nitrogenado)/química
[Mh] Termos MeSH secundário: Sítio Alostérico
Domínio Catalítico
Ácidos Cetoglutáricos/química
Substâncias Macromoleculares
Espectroscopia de Ressonância Magnética
Mutação
Fosfoenolpiruvato/química
Fosforilação
Ligação Proteica
Multimerização Proteica
Espalhamento de Radiação
Transdução de Sinais
Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, N.I.H., INTRAMURAL; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Enzymes); 0 (Ketoglutaric Acids); 0 (Macromolecular Substances); 73-89-2 (Phosphoenolpyruvate); 8ID597Z82X (alpha-ketoglutaric acid); EC 2.7.1.- (Phosphoenolpyruvate Sugar Phosphotransferase System); EC 2.7.3.- (Phosphotransferases (Nitrogenous Group Acceptor)); EC 2.7.3.9 (phosphoenolpyruvate-protein phosphotransferase)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150113
[St] Status:MEDLINE
[do] DOI:10.1038/ncomms6960


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[PMID]:24815317
[Au] Autor:Tokuhiro S; Nagataki M; Jarilla BR; Uda K; Suzuki T; Sugiura T; Agatsuma T
[Ad] Endereço:Department of Environmental Health Sciences, Kochi Medical School, Oko, Nankoku City, Kochi 783-8505, Japan.
[Ti] Título:Phosphagen kinase in Schistosoma japonicum: II. Determination of amino acid residues essential for substrate catalysis using site-directed mutagenesis.
[So] Source:Mol Biochem Parasitol;194(1-2):56-63, 2014 Mar-Apr.
[Is] ISSN:1872-9428
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Phosphagen kinases (PKs) play major roles in the regulation of energy metabolism in animals. Creatine kinase (CK) is the sole PK in vertebrates, whereas several PKs are present in invertebrates. We previously identified a contiguous dimer taurocyamine kinase (TK) from the trematode Schistosoma japonicum (Sj), a causative agent of schistosomiasis. SjTK contiguous dimer is comprised of domain 1 (D1) and domain 2 (D2). In this study, we used SjTK contiguous dimer (SjTKD1D2) or truncated single-domain constructs (SjTKD1 or SjTKD2) and employed site-directed mutagenesis to investigate the enzymatic properties of TK mutants. Mutation in SjTKD1 or SjTKD2 (D1E222G or D2E225G) caused complete loss of activity for the substrate taurocyamine. Likewise, a double mutant (D1E222GD2E225G) in the contiguous dimer (D1D2) exhibited complete loss of activity for the substrate taurocyamine. However, catalytic activity in the contiguous dimer remained in both of D1 inactive mutant (D1D2D1E222G) and D2 inactive mutant (D1D2D2E225G), suggesting that efficient catalysis of SjTKD1D2 is dependent on the activity of D1 and D2. The catalytic efficiency of the mixture of both single domains (WTD1+WTD2) showed same enzymatic properties (Km(Tauro)=0.68;Vmax/Km(Tauro)=137.04) to WTD1D2 (Km(Tauro)=0.47; Vmax/Km(Tauro)=144.30). This result suggests that the contiguous dimeric structure is not essential for the catalytic efficiencies of both domains of SjTK. Vmax/Km(Tauro) of the mixture of wild-type and inactivated domains (78.02 in WTD1+D2E225G and 128.24 in D1E222G+WTD2) were higher than the corresponding mutants (47.25 in D1D2D1E222G and 46.77 in D1D2D2E225G). To identify amino acid residues that are critical for taurocyamine binding, we performed alanine scanning mutagenesis at positions 57-63 on the guanidino specificity (GS) region of the SjTKD1, which is considered to be involved in guanidino-substrate recognition. R63A and R63Y mutants lost activity for taurocyamine, suggesting that these residues are associated with taurocyamine binding. In addition, we investigated the role of Tyr84 in D1 and found an association with substrate alignment. The Y84 residue was replaced with R, H, K, I, A, and G. Although the activities of each mutant were decreased (Vmax=2.36-67.50µmolPi/min/mgprotein), Y84 mutants possess binding affinity for taurocyamine (Km(Tauro)=3.19-10.04mM). The D1Y84R, D1Y84H, D1Y84K, and D1Y84A mutants exhibited low activity for taurocyamine, whereas the D1Y84I and D1Y84G mutants exhibited slightly decreased activity compared with the other Y84 mutants. The D1Y84K mutant lost substrate synergy between taurocyamine and ATP, suggesting that this mutation moves the position of the GS loop, similar to that of lombricine kinase (LK), and interferes with taurocyamine binding. This is the first comprehensive investigation of essential amino acid residues for substrate catalysis in trematode TK.
[Mh] Termos MeSH primário: Domínio Catalítico
Fosfotransferases (Aceptor do Grupo Nitrogenado)/genética
Fosfotransferases (Aceptor do Grupo Nitrogenado)/metabolismo
Schistosoma japonicum/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Análise Mutacional de DNA
Cinética
Dados de Sequência Molecular
Mutagênese Sítio-Dirigida
Proteínas Mutantes/genética
Proteínas Mutantes/metabolismo
Alinhamento de Sequência
Taurina/análogos & derivados
Taurina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mutant Proteins); 1EQV5MLY3D (Taurine); 543-18-0 (taurocyamine); EC 2.7.3.- (Phosphotransferases (Nitrogenous Group Acceptor)); EC 2.7.3.4 (taurocyamine kinase)
[Em] Mês de entrada:1501
[Cu] Atualização por classe:140603
[Lr] Data última revisão:
140603
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140513
[St] Status:MEDLINE


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[PMID]:24278491
[Au] Autor:Xiao JY; Lee JY; Tokuhiro S; Nagataki M; Jarilla BR; Nomura H; Kim TI; Hong SJ; Agatsuma T
[Ad] Endereço:Department of Environmental Health Sciences, Kochi Medical School, Nankoku, Kochi, Japan ; Department of Parasitology, Basic Medical College, Jiamusi University, Jiamusi, China.
[Ti] Título:Molecular cloning and characterization of taurocyamine kinase from Clonorchis sinensis: a candidate chemotherapeutic target.
[So] Source:PLoS Negl Trop Dis;7(11):e2548, 2013 Nov.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Adult Clonorchis sinensis lives in the bile duct and causes endemic clonorchiasis in East Asian countries. Phosphagen kinases (PK) constitute a highly conserved family of enzymes, which play a role in ATP buffering in cells, and are potential targets for chemotherapeutic agents, since variants of PK are found only in invertebrate animals, including helminthic parasites. This work is conducted to characterize a PK from C. sinensis and to address further investigation for future drug development. METHODOLOGY/PRINCIPAL FINDINGS: [corrected] A cDNA clone encoding a putative polypeptide of 717 amino acids was retrieved from a C. sinensis transcriptome. This polypeptide was homologous to taurocyamine kinase (TK) of the invertebrate animals and consisted of two contiguous domains. C. sinensis TK (CsTK) gene was reported and found consist of 13 exons intercalated with 12 introns. This suggested an evolutionary pathway originating from an arginine kinase gene group, and distinguished annelid TK from the general CK phylogenetic group. CsTK was found not to have a homologous counterpart in sequences analysis of its mammalian hosts from public databases. Individual domains of CsTK, as well as the whole two-domain enzyme, showed enzymatic activity and specificity toward taurocyamine substrate. Of the CsTK residues, R58, I60 and Y84 of domain 1, and H60, I63 and Y87 of domain 2 were found to participate in binding taurocyamine. CsTK expression was distributed in locomotive and reproductive organs of adult C. sinensis. Developmentally, CsTK was stably expressed in both the adult and metacercariae stages. Recombinant CsTK protein was found to have low sensitivity and specificity toward C. sinensis and platyhelminth-infected human sera on ELISA. CONCLUSION: CsTK is a promising anti-C. sinensis drug target since the enzyme is found only in the C. sinensis and has a substrate specificity for taurocyamine, which is different from its mammalian counterpart, creatine.
[Mh] Termos MeSH primário: Clonorchis sinensis/enzimologia
Fosfotransferases (Aceptor do Grupo Nitrogenado)/metabolismo
[Mh] Termos MeSH secundário: Animais
Clonagem Molecular
Clonorchis sinensis/genética
Análise por Conglomerados
Éxons
Feminino
Perfilação da Expressão Gênica
Seres Humanos
Íntrons
Masculino
Camundongos Endogâmicos BALB C
Dados de Sequência Molecular
Fosfotransferases (Aceptor do Grupo Nitrogenado)/genética
Filogenia
Ligação Proteica
Coelhos
Análise de Sequência de DNA
Homologia de Sequência
Especificidade por Substrato
Taurina/análogos & derivados
Taurina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
1EQV5MLY3D (Taurine); 543-18-0 (taurocyamine); EC 2.7.3.- (Phosphotransferases (Nitrogenous Group Acceptor)); EC 2.7.3.4 (taurocyamine kinase)
[Em] Mês de entrada:1407
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131127
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0002548



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