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  1 / 20418 MEDLINE  
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[PMID]:29202688
[Au] Autor:Abrahamian M; Kagda M; Ah-Fong AMV; Judelson HS
[Ad] Endereço:Department of Microbiology and Plant Pathology, University of California, Riverside, CA, 92521, USA.
[Ti] Título:Rethinking the evolution of eukaryotic metabolism: novel cellular partitioning of enzymes in stramenopiles links serine biosynthesis to glycolysis in mitochondria.
[So] Source:BMC Evol Biol;17(1):241, 2017 Dec 04.
[Is] ISSN:1471-2148
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: An important feature of eukaryotic evolution is metabolic compartmentalization, in which certain pathways are restricted to the cytosol or specific organelles. Glycolysis in eukaryotes is described as a cytosolic process. The universality of this canon has been challenged by recent genome data that suggest that some glycolytic enzymes made by stramenopiles bear mitochondrial targeting peptides. RESULTS: Mining of oomycete, diatom, and brown algal genomes indicates that stramenopiles encode two forms of enzymes for the second half of glycolysis, one with and the other without mitochondrial targeting peptides. The predicted mitochondrial targeting was confirmed by using fluorescent tags to localize phosphoglycerate kinase, phosphoglycerate mutase, and pyruvate kinase in Phytophthora infestans, the oomycete that causes potato blight. A genome-wide search for other enzymes with atypical mitochondrial locations identified phosphoglycerate dehydrogenase, phosphoserine aminotransferase, and phosphoserine phosphatase, which form a pathway for generating serine from the glycolytic intermediate 3-phosphoglycerate. Fluorescent tags confirmed the delivery of these serine biosynthetic enzymes to P. infestans mitochondria. A cytosolic form of this serine biosynthetic pathway, which occurs in most eukaryotes, is missing from oomycetes and most other stramenopiles. The glycolysis and serine metabolism pathways of oomycetes appear to be mosaics of enzymes with different ancestries. While some of the noncanonical oomycete mitochondrial enzymes have the closest affinity in phylogenetic analyses with proteins from other stramenopiles, others cluster with bacterial, plant, or animal proteins. The genes encoding the mitochondrial phosphoglycerate kinase and serine-forming enzymes are physically linked on oomycete chromosomes, which suggests a shared origin. CONCLUSIONS: Stramenopile metabolism appears to have been shaped through the acquisition of genes by descent and lateral or endosymbiotic gene transfer, along with the targeting of the proteins to locations that are novel compared to other eukaryotes. Colocalization of the glycolytic and serine biosynthesis enzymes in mitochondria is apparently necessary since they share a common intermediate. The results indicate that descriptions of metabolism in textbooks do not cover the full diversity of eukaryotic biology.
[Mh] Termos MeSH primário: Evolução Biológica
Células Eucarióticas/metabolismo
Glicólise
Mitocôndrias/metabolismo
Serina/biossíntese
Estramenópilas/enzimologia
Estramenópilas/metabolismo
[Mh] Termos MeSH secundário: Animais
Citosol
Genes
Mitocôndrias/genética
Oomicetos/metabolismo
Fosforilação
Filogenia
Phytophthora infestans/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
452VLY9402 (Serine)
[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:171206
[St] Status:MEDLINE
[do] DOI:10.1186/s12862-017-1087-8


  2 / 20418 MEDLINE  
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[PMID]:28468956
[Au] Autor:Jasnovidova O; Krejcikova M; Kubicek K; Stefl R
[Ad] Endereço:CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic olga.jasnovidova@ceitec.muni.cz richard.stefl@ceitec.muni.cz.
[Ti] Título:Structural insight into recognition of phosphorylated threonine-4 of RNA polymerase II C-terminal domain by Rtt103p.
[So] Source:EMBO Rep;18(6):906-913, 2017 Jun.
[Is] ISSN:1469-3178
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Phosphorylation patterns of the C-terminal domain (CTD) of largest subunit of RNA polymerase II (called the CTD code) orchestrate the recruitment of RNA processing and transcription factors. Recent studies showed that not only serines and tyrosines but also threonines of the CTD can be phosphorylated with a number of functional consequences, including the interaction with yeast transcription termination factor, Rtt103p. Here, we report the solution structure of the Rtt103p CTD-interacting domain (CID) bound to Thr4 phosphorylated CTD, a poorly understood letter of the CTD code. The structure reveals a direct recognition of the phospho-Thr4 mark by Rtt103p CID and extensive interactions involving residues from three repeats of the CTD heptad. Intriguingly, Rtt103p's CID binds equally well Thr4 and Ser2 phosphorylated CTD A doubly phosphorylated CTD at Ser2 and Thr4 diminishes its binding affinity due to electrostatic repulsion. Our structural data suggest that the recruitment of a CID-containing CTD-binding factor may be coded by more than one letter of the CTD code.
[Mh] Termos MeSH primário: RNA Polimerase II/química
Proteínas de Saccharomyces cerevisiae/química
Treonina/química
Fatores de Transcrição/química
[Mh] Termos MeSH secundário: Fosforilação
Ligação Proteica
Proteínas Quinases/metabolismo
Estrutura Terciária de Proteína
Proteólise
RNA Polimerase II/metabolismo
Proteínas de Saccharomyces cerevisiae/metabolismo
Serina/metabolismo
Treonina/metabolismo
Fatores de Transcrição/metabolismo
Transcrição Genética
Tirosina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Rtt103 protein, S cerevisiae); 0 (Saccharomyces cerevisiae Proteins); 0 (Transcription Factors); 2ZD004190S (Threonine); 42HK56048U (Tyrosine); 452VLY9402 (Serine); EC 2.7.- (Protein Kinases); EC 2.7.7.- (RNA Polymerase II)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.15252/embr.201643723


  3 / 20418 MEDLINE  
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[PMID]:29217195
[Au] Autor:Bo T; Yamamori T; Suzuki M; Sakai Y; Yamamoto K; Inanami O
[Ad] Endereço:Laboratory of Radiation Biology, Department of Applied Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
[Ti] Título:Calmodulin-dependent protein kinase II (CaMKII) mediates radiation-induced mitochondrial fission by regulating the phosphorylation of dynamin-related protein 1 (Drp1) at serine 616.
[So] Source:Biochem Biophys Res Commun;495(2):1601-1607, 2018 01 08.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mitochondrial dynamics are suggested to be indispensable for the maintenance of cellular quality and function in response to various stresses. While ionizing radiation (IR) stimulates mitochondrial fission, which is mediated by the mitochondrial fission protein, dynamin-related protein 1 (Drp1), it remains unclear how IR promotes Drp1 activation and subsequent mitochondrial fission. Therefore, we conducted this study to investigate these concerns. First, we found that X-irradiation triggered Drp1 phosphorylation at serine 616 (S616) but not at serine 637 (S637). Reconstitution analysis revealed that introduction of wild-type (WT) Drp1 recovered radiation-induced mitochondrial fission, which was absent in Drp1-deficient cells. Compared with cells transfected with WT or S637A Drp1, the change in mitochondrial shape following irradiation was mitigated in S616A Drp1-transfected cells. Furthermore, inhibition of CaMKII significantly suppressed Drp1 S616 phosphorylation and mitochondrial fission induced by IR. These results suggest that Drp1 phosphorylation at S616, but not at S637, is prerequisite for radiation-induced mitochondrial fission and that CaMKII regulates Drp1 phosphorylation at S616 following irradiation.
[Mh] Termos MeSH primário: Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo
Dinaminas/metabolismo
Dinâmica Mitocondrial/fisiologia
Dinâmica Mitocondrial/efeitos da radiação
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Benzilaminas/farmacologia
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/antagonistas & inibidores
Células Cultivadas
Dinaminas/química
Dinaminas/genética
Camundongos
Mitocôndrias/metabolismo
Mitocôndrias/efeitos da radiação
Dinâmica Mitocondrial/efeitos dos fármacos
Mutagênese Sítio-Dirigida
Fosforilação/efeitos dos fármacos
Fosforilação/efeitos da radiação
Inibidores de Proteínas Quinases/farmacologia
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Serina/química
Sulfonamidas/farmacologia
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Benzylamines); 0 (KN 92); 0 (Protein Kinase Inhibitors); 0 (Recombinant Proteins); 0 (Sulfonamides); 139298-40-1 (KN 93); 452VLY9402 (Serine); EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2); EC 3.6.5.5 (Dnm1l protein, mouse); EC 3.6.5.5 (Dynamins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE


  4 / 20418 MEDLINE  
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[PMID]:29186342
[Au] Autor:Vandenbeek R; Khan NP; Estall JL
[Ad] Endereço:Institut de recherches cliniques de Montreal, Montreal, Quebec, Canada.
[Ti] Título:Linking Metabolic Disease With the PGC-1α Gly482Ser Polymorphism.
[So] Source:Endocrinology;159(2):853-865, 2018 02 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) is a highly conserved transcriptional coactivator enriched in metabolically active tissues including liver, adipose, pancreas, and muscle. It plays a role in regulating whole body energy metabolism and its deregulation has been implicated in type 2 diabetes (T2D). A single nucleotide variant of the PPARGC1A gene (rs8192678) is associated with T2D susceptibility, relative risk of obesity and insulin resistance, and lower indices of ß cell function. This common polymorphism is within a highly conserved region of the bioactive protein and leads to a single amino acid substitution (glycine 482 to serine). Its prevalence and effects on metabolic parameters appear to vary depending on factors including ethnicity and sex, suggesting important interactions between genetics and cultural/environmental factors and associated disease risk. Interestingly, carriers of the serine allele respond better to some T2D interventions, illustrating the importance of understanding functional impacts of genetic variance on PGC-1α when targeting this pathway for personalized medicine. This review summarizes a growing body of literature surrounding possible links between the PGC-1α Gly482Ser single nucleotide polymorphism and diabetes, with focus on key clinical findings, affected metabolic systems, potential molecular mechanisms, and the influence of geographical or ethnic background on associated risk.
[Mh] Termos MeSH primário: Doenças Metabólicas/genética
Mutação de Sentido Incorreto
Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética
Polimorfismo de Nucleotídeo Único
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Diabetes Mellitus Tipo 2/genética
Ligação Genética
Predisposição Genética para Doença
Glicina/genética
Seres Humanos
Resistência à Insulina/genética
Obesidade/genética
Serina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (PPARGC1A protein, human); 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha); 452VLY9402 (Serine); TE7660XO1C (Glycine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-00872


  5 / 20418 MEDLINE  
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[PMID]:29305868
[Au] Autor:Tominaga A; Sato M; Takahashi T; Toyoda E; Toyoda K; Suzuki T; Takahashi M; Watanabe M; Okazaki K
[Ad] Endereço:Department of Orthopaedic Surgery, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjuku-ku, Tokyo, 162-8666, Japan.
[Ti] Título:Quality assessment of cellular and tissue-based products using liquid chromatography-tandem mass spectrometry.
[So] Source:Biochem Biophys Res Commun;496(2):429-435, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We are currently conducting clinical research on cell sheets for cartilage regeneration. One issue with the future use of chondrocyte sheets as cellular and tissue-based products is quality assessment. Currently, chondrocyte sheets are evaluated using invasive methods that cannot be performed on every sheet produced. We report here on our liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique that allows the noninvasive assessment of every sheet using only 50 µl of culture medium. We found that LC-MS/MS could be used to confirm cell sheet viability through the measurement of glucose and glutamine uptake, to estimate extracellular matrix production by measuring serine consumption, to estimate cell kinetics by measuring cytidine and uracil concentrations, and to estimate melanoma inhibitory activity level by measuring pyridoxal concentration. LC-MS/MS may be useful for the noninvasive assessment of products to be used in regenerative medicine.
[Mh] Termos MeSH primário: Cartilagem/metabolismo
Condrócitos/metabolismo
Cromatografia Líquida/normas
Regeneração/fisiologia
Espectrometria de Massas em Tandem/normas
[Mh] Termos MeSH secundário: Transporte Biológico
Cartilagem/patologia
Cartilagem/cirurgia
Citidina/metabolismo
Matriz Extracelular
Glucose/metabolismo
Glutamina/metabolismo
Seres Humanos
Controle de Qualidade
Medicina Regenerativa/métodos
Serina/metabolismo
Uracila/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0RH81L854J (Glutamine); 452VLY9402 (Serine); 56HH86ZVCT (Uracil); 5CSZ8459RP (Cytidine); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180107
[St] Status:MEDLINE


  6 / 20418 MEDLINE  
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[PMID]:29223392
[Au] Autor:Fujimoto T; Kuwahara T; Eguchi T; Sakurai M; Komori T; Iwatsubo T
[Ad] Endereço:Department of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.
[Ti] Título:Parkinson's disease-associated mutant LRRK2 phosphorylates Rab7L1 and modifies trans-Golgi morphology.
[So] Source:Biochem Biophys Res Commun;495(2):1708-1715, 2018 01 08.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mutations in leucine-rich repeat kinase 2 (LRRK2) are the major genetic cause of autosomal-dominantly inherited Parkinson's disease. LRRK2 is implicated in the regulation of intracellular trafficking, neurite outgrowth and PD risk in connection with Rab7L1, a putative interactor of LRRK2. Recently, a subset of Rab GTPases have been reported as substrates of LRRK2. Here we examine the kinase activity of LRRK2 on Rab7L1 in situ in cells. Phos-tag analyses and metabolic labeling assays revealed that LRRK2 readily phosphorylates Golgi-localized wild-type Rab7L1 but not mutant forms that are distributed in the cytoplasm. In vitro assays demonstrated direct phosphorylation of Rab7L1 by LRRK2. Subsequent screening using Rab7L1 mutants harboring alanine-substitution for every single Ser/Thr residue revealed that Ser72 is a major phosphorylation site, which was confirmed by using a phospho-Ser72-specific antibody. Moreover, LRRK2 pathogenic Parkinson mutants altogether markedly enhanced the phosphorylation at Ser72. The modulation of Ser72 phosphorylation in Rab7L1 resulted in an alteration of the morphology and distribution of the trans-Golgi network. These data collectively support the involvement of Rab7L1 phosphorylation in the LRRK2-mediated cellular and pathogenetic mechanisms.
[Mh] Termos MeSH primário: Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética
Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo
Mutação
Doença de Parkinson/genética
Doença de Parkinson/metabolismo
Proteínas rab1 de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Substituição de Aminoácidos
Sítios de Ligação/genética
Células HEK293
Células HeLa
Seres Humanos
Modelos Moleculares
Proteínas Mutantes/genética
Proteínas Mutantes/metabolismo
Doença de Parkinson/patologia
Fosforilação
Conformação Proteica
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/genética
Proteínas Recombinantes de Fusão/metabolismo
Serina/química
Serina/genética
Especificidade por Substrato
Proteínas rab1 de Ligação ao GTP/química
Proteínas rab1 de Ligação ao GTP/genética
Rede trans-Golgi/metabolismo
Rede trans-Golgi/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Mutant Proteins); 0 (Rab29 protein, human); 0 (Recombinant Fusion Proteins); 452VLY9402 (Serine); EC 2.7.11.1 (LRRK2 protein, human); EC 2.7.11.1 (Leucine-Rich Repeat Serine-Threonine Protein Kinase-2); EC 3.6.5.2 (rab1 GTP-Binding Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171211
[St] Status:MEDLINE


  7 / 20418 MEDLINE  
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[PMID]:28467058
[Au] Autor:Bouzon M; Perret A; Loreau O; Delmas V; Perchat N; Weissenbach J; Taran F; Marlière P
[Ad] Endereço:CEA, Genoscope , 2 rue Gaston Crémieux, 91000 Evry, France.
[Ti] Título:A Synthetic Alternative to Canonical One-Carbon Metabolism.
[So] Source:ACS Synth Biol;6(8):1520-1533, 2017 Aug 18.
[Is] ISSN:2161-5063
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:One-carbon metabolism is an ubiquitous metabolic pathway that encompasses the reactions transferring formyl-, hydroxymethyl- and methyl-groups bound to tetrahydrofolate for the synthesis of purine nucleotides, thymidylate, methionine and dehydropantoate, the precursor of coenzyme A. An alternative cyclic pathway was designed that substitutes 4-hydroxy-2-oxobutanoic acid (HOB), a compound absent from known metabolism, for the amino acids serine and glycine as one-carbon donors. It involves two novel reactions, the transamination of l-homoserine and the transfer of a one-carbon unit from HOB to tetrahydrofolate releasing pyruvate as coproduct. Since canonical reactions regenerate l-homoserine from pyruvate by carboxylation and subsequent reduction, every one-carbon moiety made available for anabolic reactions originates from CO . The HOB-dependent pathway was established in an Escherichia coli auxotroph selected for prototrophy using long-term cultivation protocols. Genetic, metabolic and biochemical evidence support the emergence of a functional HOB-dependent one-carbon pathway achieved with the recruitment of the two enzymes l-homoserine transaminase and HOB-hydroxymethyltransferase and of HOB as an essential metabolic intermediate. Escherichia coli biochemical reprogramming was achieved by minimally altering canonical metabolism and leveraging on natural selection mechanisms, thereby launching the resulting strain on an evolutionary trajectory diverging from all known extant species.
[Mh] Termos MeSH primário: Acetoacetatos/metabolismo
Carbono/metabolismo
Proteínas de Escherichia coli/metabolismo
Escherichia coli/metabolismo
Melhoramento Genético/métodos
Engenharia Metabólica/métodos
Redes e Vias Metabólicas/genética
[Mh] Termos MeSH secundário: Escherichia coli/genética
Proteínas de Escherichia coli/genética
Glicina/genética
Glicina/metabolismo
Ácido Pirúvico/metabolismo
Serina/genética
Serina/metabolismo
Biologia Sintética/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetoacetates); 0 (Escherichia coli Proteins); 452VLY9402 (Serine); 4ZI204Y1MC (acetoacetic acid); 7440-44-0 (Carbon); 8558G7RUTR (Pyruvic Acid); TE7660XO1C (Glycine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1021/acssynbio.7b00029


  8 / 20418 MEDLINE  
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[PMID]:28448716
[Au] Autor:Zhang SY; Sperlich B; Li FY; Al-Ayoubi S; Chen HX; Zhao YF; Li YM; Weise K; Winter R; Chen YX
[Ad] Endereço:Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University , Beijing 100084, China.
[Ti] Título:Phosphorylation Weakens but Does Not Inhibit Membrane Binding and Clustering of K-Ras4B.
[So] Source:ACS Chem Biol;12(6):1703-1710, 2017 06 16.
[Is] ISSN:1554-8937
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:K-Ras4B is one of the most frequently mutated Ras isoforms in cancer. The signaling activity of K-Ras4B depends on its localization to the plasma membrane (PM), which is mainly mediated by its polybasic farnesylated C-terminus. On top of the constitutive cycles that maintain the PM enrichment of K-Ras4B, conditional phosphorylation at Ser181 located within this motif has been found to be involved in regulating K-Ras4B's cell distribution and signaling activity. However, discordant observations have undermined our understanding of the role this phosphorylation plays. Here, we report an efficient strategy for producing K-Ras4B simultaneously bearing phosphate, farnesyl, and methyl modifications on a preparative scale, a very useful in vitro system when used in concert with model biomembranes. By using this system, we determined that phosphorylation at Ser181 does not fully inhibit membrane binding and clustering of K-Ras4B but reduces its membrane binding affinity, depending on membrane fluidity. In addition, phosphorylated K-Ras4B maintains tight association with its cytosolic shuttle protein PDEδ. After delivering K-Ras4B containing nonhydrolyzable phosphoserine mimetic into cells, the protein displayed a decreasing PM distribution compared with nonphosphorylable K-Ras4B, implying that phosphorylation might facilitate the dissociation of K-Ras4B from the PM. In addition, phosphorylation does not alter the localization of K-Ras4B in the liquid-disordered lipid subdomains of the membrane but slightly alters the thermotropic properties of K-Ras4B-incorporated membranes probably due to minor differences in membrane partitioning and dynamics. These results provide novel mechanistic insights into the role that phosphorylation at Ser181 plays in regulating K-Ras4B's distribution and activity.
[Mh] Termos MeSH primário: Membrana Celular/metabolismo
Proteínas Proto-Oncogênicas p21(ras)/metabolismo
[Mh] Termos MeSH secundário: Seres Humanos
Modelos Biológicos
Fosforilação/fisiologia
Agregados Proteicos
Serina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Protein Aggregates); 452VLY9402 (Serine); EC 3.6.1.- (K-Ras4B protein, human); EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1021/acschembio.7b00165


  9 / 20418 MEDLINE  
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[PMID]:29324779
[Au] Autor:Price MN; Zane GM; Kuehl JV; Melnyk RA; Wall JD; Deutschbauer AM; Arkin AP
[Ad] Endereço:Environmental Genomics & Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.
[Ti] Título:Filling gaps in bacterial amino acid biosynthesis pathways with high-throughput genetics.
[So] Source:PLoS Genet;14(1):e1007147, 2018 01.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:For many bacteria with sequenced genomes, we do not understand how they synthesize some amino acids. This makes it challenging to reconstruct their metabolism, and has led to speculation that bacteria might be cross-feeding amino acids. We studied heterotrophic bacteria from 10 different genera that grow without added amino acids even though an automated tool predicts that the bacteria have gaps in their amino acid synthesis pathways. Across these bacteria, there were 11 gaps in their amino acid biosynthesis pathways that we could not fill using current knowledge. Using genome-wide mutant fitness data, we identified novel enzymes that fill 9 of the 11 gaps and hence explain the biosynthesis of methionine, threonine, serine, or histidine by bacteria from six genera. We also found that the sulfate-reducing bacterium Desulfovibrio vulgaris synthesizes homocysteine (which is a precursor to methionine) by using DUF39, NIL/ferredoxin, and COG2122 proteins, and that homoserine is not an intermediate in this pathway. Our results suggest that most free-living bacteria can likely make all 20 amino acids and illustrate how high-throughput genetics can uncover previously-unknown amino acid biosynthesis genes.
[Mh] Termos MeSH primário: Aminoácidos/biossíntese
Aminoácidos/genética
Bactérias/genética
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Processos Heterotróficos
Sequenciamento de Nucleotídeos em Larga Escala/métodos
Histidina/biossíntese
Metionina/biossíntese
Análise de Sequência de DNA/métodos
Serina/biossíntese
Treonina/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amino Acids); 0 (Bacterial Proteins); 2ZD004190S (Threonine); 452VLY9402 (Serine); 4QD397987E (Histidine); AE28F7PNPL (Methionine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007147


  10 / 20418 MEDLINE  
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[PMID]:27778288
[Au] Autor:Baggelaar MP; Van der Stelt M
[Ad] Endereço:Department of Bio-organic Synthesis, Leiden University, 9500, Einsteinweg 55, 2333 CC, Leiden, The Netherlands. m.p.baggelaar@chem.leidenuniv.nl.
[Ti] Título:Competitive ABPP of Serine Hydrolases: A Case Study on DAGL-Alpha.
[So] Source:Methods Mol Biol;1491:161-169, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Competitive activity-based protein profiling is a highly efficient chemical biology technique to determine target engagement and selectivity profiles of enzyme inhibitors in complex proteomes. Fluorophosphonate-based fluorescent inhibitors are widely used as broad-spectrum probes for serine hydrolases. However, diacylglycerol lipase-α is not labeled by fluorophosphonate-based probes. To overcome this problem, we have developed a tailor-made activity-based probe that reacts with diacylglycerol lipase-α. Here we describe a case study in which we apply competitive activity-based protein profiling using a broad-spectrum and a tailor-made activity-based probe to establish selectivity and activity profiles of inhibitors targeting diacylglycerol lipase-α in the mouse brain proteome.
[Mh] Termos MeSH primário: Hidrolases/metabolismo
Lipase Lipoproteica/metabolismo
Serina/química
[Mh] Termos MeSH secundário: Animais
Encéfalo/enzimologia
Encéfalo/metabolismo
Hidrolases/química
Camundongos
Proteoma
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Proteome); 452VLY9402 (Serine); EC 3.- (Hydrolases); EC 3.1.1.34 (Lipoprotein Lipase); EC 3.1.1.34 (diacylglycerol lipase alpha, human)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE



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