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[PMID]:28807574
[Au] Autor:Brockway AJ; Volkov OA; Cosner CC; MacMillan KS; Wring SA; Richardson TE; Peel M; Phillips MA; De Brabander JK
[Ad] Endereço:Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9038, USA.
[Ti] Título:Synthesis and evaluation of analogs of 5'-(((Z)-4-amino-2-butenyl)methylamino)-5'-deoxyadenosine (MDL 73811, or AbeAdo) - An inhibitor of S-adenosylmethionine decarboxylase with antitrypanosomal activity.
[So] Source:Bioorg Med Chem;25(20):5433-5440, 2017 Oct 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We describe our efforts to improve the pharmacokinetic properties of a mechanism-based suicide inhibitor of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (AdoMetDC), essential for the survival of the eukaryotic parasite Trypanosoma brucei responsible for Human African Trypanosomiasis (HAT). The lead compound, 5'-(((Z)-4-amino-2-butenyl)methylamino)-5'-deoxyadenosine (1, also known as MDL 73811, or AbeAdo), has curative efficacy at a low dosage in a hemolymphatic model of HAT but displayed no demonstrable effect in a mouse model of the CNS stage of HAT due to poor blood-brain barrier permeation. Therefore, we prepared and evaluated an extensive set of analogs with modifications in the aminobutenyl side chain, the 5'-amine, the ribose, and the purine fragments. Although we gained valuable structure-activity insights from this comprehensive dataset, we did not gain traction on improving the prospects for CNS penetration while retaining the potent antiparasitic activity and metabolic stability of the lead compound 1.
[Mh] Termos MeSH primário: Adenosilmetionina Descarboxilase/antagonistas & inibidores
Desoxiadenosinas/farmacologia
Inibidores Enzimáticos/farmacologia
Tripanossomicidas/farmacologia
Trypanosoma brucei brucei/efeitos dos fármacos
Tripanossomíase Africana/tratamento farmacológico
[Mh] Termos MeSH secundário: Adenosilmetionina Descarboxilase/metabolismo
Animais
Desoxiadenosinas/síntese química
Desoxiadenosinas/química
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Inibidores Enzimáticos/síntese química
Inibidores Enzimáticos/química
Camundongos
Conformação Molecular
Testes de Sensibilidade Parasitária
Relação Estrutura-Atividade
Tripanossomicidas/síntese química
Tripanossomicidas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Deoxyadenosines); 0 (Enzyme Inhibitors); 0 (Trypanocidal Agents); 7GI49JB39O (MDL 73811); EC 4.1.1.50 (Adenosylmethionine Decarboxylase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170816
[St] Status:MEDLINE


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[PMID]:28658205
[Au] Autor:Zabala-Letona A; Arruabarrena-Aristorena A; Martín-Martín N; Fernandez-Ruiz S; Sutherland JD; Clasquin M; Tomas-Cortazar J; Jimenez J; Torres I; Quang P; Ximenez-Embun P; Bago R; Ugalde-Olano A; Loizaga-Iriarte A; Lacasa-Viscasillas I; Unda M; Torrano V; Cabrera D; van Liempd SM; Cendon Y; Castro E; Murray S; Revandkar A; Alimonti A; Zhang Y; Barnett A; Lein G; Pirman D; Cortazar AR; Arreal L; Prudkin L; Astobiza I; Valcarcel-Jimenez L; Zuñiga-García P; Fernandez-Dominguez I; Piva M; Caro-Maldonado A; Sánchez-Mosquera P; Castillo-Martín M; Serra V; Beraza N; Gentilella A; Thomas G; Azkargorta M; Elortza F; Farràs R; Olmos D; Efeyan A; Anguita J; Muñoz J
[Ad] Endereço:CIC bioGUNE, Bizkaia Technology Park, 801 building, 48160, Derio, Spain.
[Ti] Título:mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer.
[So] Source:Nature;547(7661):109-113, 2017 07 06.
[Is] ISSN:1476-4687
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Activation of the PTEN-PI3K-mTORC1 pathway consolidates metabolic programs that sustain cancer cell growth and proliferation. Here we show that mechanistic target of rapamycin complex 1 (mTORC1) regulates polyamine dynamics, a metabolic route that is essential for oncogenicity. By using integrative metabolomics in a mouse model and human biopsies of prostate cancer, we identify alterations in tumours affecting the production of decarboxylated S-adenosylmethionine (dcSAM) and polyamine synthesis. Mechanistically, this metabolic rewiring stems from mTORC1-dependent regulation of S-adenosylmethionine decarboxylase 1 (AMD1) stability. This novel molecular regulation is validated in mouse and human cancer specimens. AMD1 is upregulated in human prostate cancer with activated mTORC1. Conversely, samples from a clinical trial with the mTORC1 inhibitor everolimus exhibit a predominant decrease in AMD1 immunoreactivity that is associated with a decrease in proliferation, in line with the requirement of dcSAM production for oncogenicity. These findings provide fundamental information about the complex regulatory landscape controlled by mTORC1 to integrate and translate growth signals into an oncogenic metabolic program.
[Mh] Termos MeSH primário: Adenosilmetionina Descarboxilase/metabolismo
Complexos Multiproteicos/metabolismo
Poliaminas/metabolismo
Neoplasias da Próstata/metabolismo
Serina-Treonina Quinases TOR/metabolismo
[Mh] Termos MeSH secundário: Adenosilmetionina Descarboxilase/imunologia
Animais
Proliferação Celular
Ativação Enzimática
Everolimo/uso terapêutico
Seres Humanos
Masculino
Alvo Mecanístico do Complexo 1 de Rapamicina
Metabolômica
Camundongos
Complexos Multiproteicos/antagonistas & inibidores
PTEN Fosfo-Hidrolase/metabolismo
Fosfatidilinositol 3-Quinases/metabolismo
Neoplasias da Próstata/tratamento farmacológico
Neoplasias da Próstata/patologia
Estabilidade Proteica
S-Adenosilmetionina/análogos & derivados
S-Adenosilmetionina/metabolismo
Serina-Treonina Quinases TOR/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Multiprotein Complexes); 0 (Polyamines); 22365-13-5 (S-adenosyl-3-methylthiopropylamine); 7LP2MPO46S (S-Adenosylmethionine); 9HW64Q8G6G (Everolimus); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1); EC 3.1.3.67 (PTEN Phosphohydrolase); EC 3.1.3.67 (PTEN protein, human); EC 4.1.1.50 (AMD1 protein, human); EC 4.1.1.50 (Adenosylmethionine Decarboxylase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170629
[St] Status:MEDLINE
[do] DOI:10.1038/nature22964


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[PMID]:28546427
[Au] Autor:Hobley L; Li B; Wood JL; Kim SH; Naidoo J; Ferreira AS; Khomutov M; Khomutov A; Stanley-Wall NR; Michael AJ
[Ad] Endereço:From the Departments of Pharmacology and.
[Ti] Título:Spermidine promotes biofilm formation by activating expression of the matrix regulator .
[So] Source:J Biol Chem;292(29):12041-12053, 2017 Jul 21.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ubiquitous polyamine spermidine is not required for normal planktonic growth of but is essential for robust biofilm formation. However, the structural features of spermidine required for biofilm formation are unknown and so are the molecular mechanisms of spermidine-stimulated biofilm development. We report here that in a spermidine-deficient mutant, the structural analogue norspermidine, but not homospermidine, restored biofilm formation. Intracellular biosynthesis of another spermidine analogue, aminopropylcadaverine, from exogenously supplied homoagmatine also restored biofilm formation. The differential ability of C-methylated spermidine analogues to functionally replace spermidine in biofilm formation indicated that the aminopropyl moiety of spermidine is more sensitive to -methylation, which it is essential for biofilm formation, but that the length and symmetry of the molecule is not critical. Transcriptomic analysis of a spermidine-depleted mutant uncovered a nitrogen-, methionine-, and -adenosylmethionine-sufficiency response, resulting in repression of gene expression related to purine catabolism, methionine and -adenosylmethionine biosynthesis and methionine salvage, and signs of altered membrane status. Consistent with the spermidine requirement in biofilm formation, single-cell analysis of this mutant indicated reduced expression of the operons for production of the exopolysaccharide and TasA protein biofilm matrix components and SinR antagonist Deletion of or ectopic expression of in the spermidine-deficient Δ background restored biofilm formation, indicating that spermidine is required for expression of the biofilm regulator Our results indicate that spermidine functions in biofilm development by activating transcription of the biofilm matrix exopolysaccharide and TasA operons through the regulator .
[Mh] Termos MeSH primário: Bacillus subtilis/fisiologia
Proteínas de Bactérias/agonistas
Biofilmes/crescimento & desenvolvimento
Regulação Bacteriana da Expressão Gênica
Polissacarídeos Bacterianos/biossíntese
Espermidina/metabolismo
Fatores de Transcrição/agonistas
[Mh] Termos MeSH secundário: Adenosilmetionina Descarboxilase/genética
Adenosilmetionina Descarboxilase/metabolismo
Bacillus subtilis/citologia
Bacillus subtilis/genética
Bacillus subtilis/crescimento & desenvolvimento
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Cadaverina/análogos & derivados
Cadaverina/metabolismo
Deleção de Genes
Perfilação da Expressão Gênica
Metionina/metabolismo
Metilação
Ciclo do Nitrogênio
Óperon
Purinas/metabolismo
S-Adenosilmetionina/metabolismo
Análise de Célula Única
Espermidina/análogos & derivados
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Polysaccharides, Bacterial); 0 (Purines); 0 (Transcription Factors); 0 (exopolysaccharide, Bacillus); 56-18-8 (norspermidine); 56-19-9 (N-(3-aminopropyl)cadaverine); 7LP2MPO46S (S-Adenosylmethionine); AE28F7PNPL (Methionine); EC 4.1.1.50 (Adenosylmethionine Decarboxylase); L90BEN6OLL (Cadaverine); U87FK77H25 (Spermidine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170527
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.789644


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[PMID]:28178573
[Au] Autor:Liu Z; Liu P; Qi D; Peng X; Liu G
[Ad] Endereço:Key Laboratory of Plant Resources, Institute of Botany, The Chinese Academy of Sciences, Beijing, 100093, People's Republic of China; University of the Chinese Academy of Sciences, Beijing, 100049, People's Republic of China. Electronic address: liuzhujiang1986@163.com.
[Ti] Título:Enhancement of cold and salt tolerance of Arabidopsis by transgenic expression of the S-adenosylmethionine decarboxylase gene from Leymus chinensis.
[So] Source:J Plant Physiol;211:90-99, 2017 Apr.
[Is] ISSN:1618-1328
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Leymus chinensis is an important perennial forage grass natively distributed in the Eurasian Steppe. However, little is known about the molecular mechanism of its adaptation to extreme environmental conditions. Based on L. chinensis cold-treated sequence database, a highly expressed S-adenosylmethionine decarboxylase gene (LcSAMDC1) was isolated from L. chinensis. Gene structure analysis showed that LcSAMDC1 has two introns and three exons as well as three non-overlapping ORFs in its mRNA sequence. One hour of cold exposure caused a significant up-regulation of LcSAMDC1, while abscisic acid (ABA), salt, and osmotic stresses slightly induced its expression. Analysis of gene expression in different tissues showed that LcSAMDC1 was expressed ubiquitously, with higher levels in the young spike and rhizome. Overexpression of the main ORF of LcSAMDC1 in transgenic Arabidopsis promoted increased tolerance to cold and salt stress relative to wild type Arabidopsis. The concentration of polyamines, proline, and chlorophyll was significantly higher in transgenic Arabidopsis, and spermine of polyamines increased more under cold than under salt stress. These results suggest that LcSAMDC1 was induced in response to cold and could influence the production of polyamines involved in stress tolerance of L. chinensis. Moreover, transgenic expression of LcSAMDC1 could be used to improve the abiotic resistance of crops.
[Mh] Termos MeSH primário: Adenosilmetionina Descarboxilase/genética
Arabidopsis/genética
Arabidopsis/fisiologia
Temperatura Baixa
Genes de Plantas
Poaceae/enzimologia
Poaceae/genética
Tolerância a Sal/genética
[Mh] Termos MeSH secundário: Adenosilmetionina Descarboxilase/metabolismo
Antioxidantes/metabolismo
Sequência de Bases
Clorofila/metabolismo
Etilenos/biossíntese
Fluorescência
Regulação da Expressão Gênica de Plantas
Fenótipo
Filogenia
Proteínas de Plantas/metabolismo
Plantas Geneticamente Modificadas
Poliaminas/metabolismo
Prolina/biossíntese
Estresse Fisiológico/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Ethylenes); 0 (Plant Proteins); 0 (Polyamines); 1406-65-1 (Chlorophyll); 91GW059KN7 (ethylene); 9DLQ4CIU6V (Proline); EC 4.1.1.50 (Adenosylmethionine Decarboxylase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170626
[Lr] Data última revisão:
170626
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170209
[St] Status:MEDLINE


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[PMID]:27977001
[Au] Autor:Volkov OA; Kinch L; Ariagno C; Deng X; Zhong S; Grishin N; Tomchick DR; Chen Z; Phillips MA
[Ad] Endereço:Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States.
[Ti] Título:Relief of autoinhibition by conformational switch explains enzyme activation by a catalytically dead paralog.
[So] Source:Elife;5, 2016 Dec 15.
[Is] ISSN:2050-084X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Catalytically inactive enzyme paralogs occur in many genomes. Some regulate their active counterparts but the structural principles of this regulation remain largely unknown. We report X-ray structures of -adenosylmethionine decarboxylase alone and in functional complex with its catalytically dead paralogous partner, prozyme. We show monomeric AdoMetDC is inactive because of autoinhibition by its N-terminal sequence. Heterodimerization with prozyme displaces this sequence from the active site through a complex mechanism involving a -to- proline isomerization, reorganization of a ß-sheet, and insertion of the N-terminal α-helix into the heterodimer interface, leading to enzyme activation. We propose that the evolution of this intricate regulatory mechanism was facilitated by the acquisition of the dimerization domain, a single step that can in principle account for the divergence of regulatory schemes in the AdoMetDC enzyme family. These studies elucidate an allosteric mechanism in an enzyme and a plausible scheme by which such complex cooperativity evolved.
[Mh] Termos MeSH primário: Adenosilmetionina Descarboxilase/química
Adenosilmetionina Descarboxilase/metabolismo
Ativação Enzimática
Regulação Enzimológica da Expressão Gênica
Trypanosoma brucei brucei/enzimologia
[Mh] Termos MeSH secundário: Regulação Alostérica
Cristalografia por Raios X
Modelos Moleculares
Conformação Proteica
Multimerização Proteica
Proteínas de Protozoários/química
Proteínas de Protozoários/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protozoan Proteins); EC 4.1.1.50 (Adenosylmethionine Decarboxylase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161216
[St] Status:MEDLINE


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[PMID]:27158836
[Au] Autor:Bruender NA; Bandarian V
[Ad] Endereço:Department of Chemistry, University of Utah , Salt Lake City, Utah 84112, United States.
[Ti] Título:The Radical S-Adenosyl-l-methionine Enzyme MftC Catalyzes an Oxidative Decarboxylation of the C-Terminus of the MftA Peptide.
[So] Source:Biochemistry;55(20):2813-6, 2016 May 24.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ribosomally synthesized post-translationally modified peptides (RiPPs) are encoded in the genomes of a wide variety of microorganisms, in the proximity of open reading frames that encode enzymes that conduct extensive modifications, many of which are novel. Recently, members of the radical S-adenosyl-l-methionine (SAM) superfamily have been identified in these biosynthetic clusters. Herein, we demonstrate the putative radical SAM enzyme, MftC, oxidatively decarboxylates the C-terminus of the MftA peptide in the presence of the accessory protein MftB. The reaction catalyzed by MftC expands the repertoire of peptide-based radical SAM chemistry beyond the intramolecular cross-links.
[Mh] Termos MeSH primário: Adenosilmetionina Descarboxilase/química
Proteínas de Bactérias/química
Mycobacterium smegmatis/química
Peptídeos/química
[Mh] Termos MeSH secundário: Adenosilmetionina Descarboxilase/genética
Adenosilmetionina Descarboxilase/metabolismo
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Mycobacterium smegmatis/genética
Mycobacterium smegmatis/metabolismo
Oxirredução
Peptídeos/genética
Peptídeos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Peptides); EC 4.1.1.50 (Adenosylmethionine Decarboxylase)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170524
[Lr] Data última revisão:
170524
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160510
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.6b00355


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[PMID]:27102990
[Au] Autor:Cui PF; Xing L; Qiao JB; Zhang JL; He YJ; Zhang M; Lyu JY; Luo CQ; Jin L; Jiang HL
[Ad] Endereço:State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
[Ti] Título:Polyamine metabolism-based dual functional gene delivery system to synergistically inhibit the proliferation of cancer.
[So] Source:Int J Pharm;506(1-2):79-86, 2016 Jun 15.
[Is] ISSN:1873-3476
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Polyamine content, which is associated with tumor growth, can be regulated by ornithine decarboxylase (ODC) and S-adenosyl methionine decarboxylase (SAMDC), two key enzymes in polyamine biosynthesis. Here we aim to develop a pH-responsive cationic poly(agmatine) based on a polyamine analogue-agmatine that can dually function as a gene delivery vector as well as an anticancer agent by inhibiting ODC after intracellular degradation. The core-shell nanoparticles, formed by poly(agmatine)/SAMDC siRNA complex as a core, were coated with bovine serum albumin for better in vivo circulation stability and tumor targeting. When the nanoparticles were taken up by tumor cells via endocytosis and degraded in endosome, the released agmatine and SAMDC siRNA can synergistically inhibit polyamines biosynthesis, inducing inhibition of tumor proliferation. Our study offered a potential way in tumor therapy based on polyamine metabolism.
[Mh] Termos MeSH primário: Antineoplásicos/administração & dosagem
Proliferação Celular/efeitos dos fármacos
Neoplasias/tratamento farmacológico
Poliaminas/metabolismo
[Mh] Termos MeSH secundário: Adenosilmetionina Descarboxilase/metabolismo
Linhagem Celular Tumoral
Endocitose/efeitos dos fármacos
Endossomos/metabolismo
Técnicas de Transferência de Genes
Células Hep G2
Seres Humanos
Células MCF-7
Nanopartículas/administração & dosagem
Nanopartículas/química
Neoplasias/metabolismo
Ornitina Descarboxilase/metabolismo
RNA Interferente Pequeno/metabolismo
Soroalbumina Bovina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Polyamines); 0 (RNA, Small Interfering); 27432CM55Q (Serum Albumin, Bovine); EC 4.1.1.17 (Ornithine Decarboxylase); EC 4.1.1.50 (Adenosylmethionine Decarboxylase)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160423
[St] Status:MEDLINE


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[PMID]:27031344
[Au] Autor:Makhoba XH; Burger A; Coertzen D; Zininga T; Birkholtz LM; Shonhai A
[Ad] Endereço:Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, South Africa.
[Ti] Título:Use of a Chimeric Hsp70 to Enhance the Quality of Recombinant Plasmodium falciparum S-Adenosylmethionine Decarboxylase Protein Produced in Escherichia coli.
[So] Source:PLoS One;11(3):e0152626, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:S-adenosylmethionine decarboxylase (PfAdoMetDC) from Plasmodium falciparum is a prospective antimalarial drug target. The production of recombinant PfAdoMetDC for biochemical validation as a drug target is important. The production of PfAdoMetDC in Escherichia coli has been reported to result in unsatisfactory yields and poor quality product. The co-expression of recombinant proteins with molecular chaperones has been proposed as one way to improve the production of the former in E. coli. E. coli heat shock proteins DnaK, GroEL-GroES and DnaJ have previously been used to enhance production of some recombinant proteins. However, the outcomes were inconsistent. An Hsp70 chimeric protein, KPf, which is made up of the ATPase domain of E. coli DnaK and the substrate binding domain of P. falciparum Hsp70 (PfHsp70) has been previously shown to exhibit chaperone function when it was expressed in E. coli cells whose resident Hsp70 (DnaK) function was impaired. We proposed that because of its domain constitution, KPf would most likely be recognised by E. coli Hsp70 co-chaperones. Furthermore, because it possesses a substrate binding domain of plasmodial origin, KPf would be primed to recognise recombinant PfAdoMetDC expressed in E. coli. First, using site-directed mutagenesis, followed by complementation assays, we established that KPf with a mutation in the hydrophobic residue located in its substrate binding cavity was functionally compromised. We further co-expressed PfAdoMetDC with KPf, PfHsp70 and DnaK in E. coli cells either in the absence or presence of over-expressed GroEL-GroES chaperonin. The folded and functional status of the produced PfAdoMetDC was assessed using limited proteolysis and enzyme assays. PfAdoMetDC co-expressed with KPf and PfHsp70 exhibited improved activity compared to protein co-expressed with over-expressed DnaK. Our findings suggest that chimeric KPf may be an ideal Hsp70 co-expression partner for the production of recombinant plasmodial proteins in E. coli.
[Mh] Termos MeSH primário: Adenosilmetionina Descarboxilase/genética
Proteínas de Bactérias/genética
Escherichia coli/metabolismo
Proteínas de Choque Térmico HSP70/genética
Plasmodium falciparum/genética
[Mh] Termos MeSH secundário: Adenosilmetionina Descarboxilase/metabolismo
Proteínas de Bactérias/metabolismo
Proteínas de Escherichia coli/genética
Proteínas de Escherichia coli/metabolismo
Proteínas de Choque Térmico HSP40/genética
Proteínas de Choque Térmico HSP40/metabolismo
Proteínas de Choque Térmico HSP70/metabolismo
Chaperonas Moleculares/genética
Chaperonas Moleculares/metabolismo
Ligação Proteica
Proteínas Recombinantes/biossíntese
Proteínas Recombinantes/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Escherichia coli Proteins); 0 (HSP40 Heat-Shock Proteins); 0 (HSP70 Heat-Shock Proteins); 0 (Molecular Chaperones); 0 (Recombinant Proteins); EC 3.6.1.- (dnaK protein, E coli); EC 4.1.1.50 (Adenosylmethionine Decarboxylase)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160401
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0152626


  9 / 983 MEDLINE  
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[PMID]:26757733
[Au] Autor:Mo HJ; Sun YX; Zhu XL; Wang XF; Zhang Y; Yang J; Yan GJ; Ma ZY
[Ad] Endereço:North China Key Laboratory for Germplasm Resources of Education Ministry, Hebei Agricultural University, Baoding, 071001, China.
[Ti] Título:Cotton S-adenosylmethionine decarboxylase-mediated spermine biosynthesis is required for salicylic acid- and leucine-correlated signaling in the defense response to Verticillium dahliae.
[So] Source:Planta;243(4):1023-39, 2016 Apr.
[Is] ISSN:1432-2048
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:MAIN CONCLUSION: Cotton S-adenosylmethionine decarboxylase-, rather than spermine synthase-, mediated spermine biosynthesis is required for salicylic acid- and leucine-correlated signaling in the defense response to Verticillium dahliae. Spermine (Spm) signaling is correlated with plant resistance to the fungal pathogen Verticillium dahliae. We identified genes for key rate-limiting enzymes in the biosynthesis of Spm, namely S-adenosylmethionine decarboxylase (GhSAMDC) and Spm synthase (GhSPMS). These were found by screening suppression subtractive hybridization and cDNA libraries of cotton (Gossypium) species tolerant to Verticillium wilt. Both were induced early and strongly by inoculation with V. dahliae and application of plant hormones. Silencing of GhSPMS or GhSAMDC in cotton leaves led to a significant accumulation of upstream substrates and, ultimately, enhanced plant susceptibility to Verticillium infection. Exogenous supplementation of Spm to the silenced cotton plants improved resistance. When compared with the wild type (WT), constitutive expression of GhSAMDC in Arabidopsis thaliana was associated with greater Verticillium wilt resistance and higher accumulations of Spm, salicylic acid, and leucine during the infection period. By contrast, transgenic Arabidopsis plants that over-expressed GhSPMS were unexpectedly more susceptible than the WT to V. dahliae and they also had impaired levels of putrescine (Put) and salicylic acid (SA). The susceptibility exhibited in GhSPMS-overexpressing Arabidopsis plants was partially reversed by the exogenous supply of Put or SA. In addition, the responsiveness of those two transgenic Arabidopsis lines to V. dahliae was associated with an alteration in transcripts of genes involved in plant resistance to epidermal penetrations and amino acid signaling. Together, these results suggest that GhSAMDC-, rather than GhSPMS-, mediated spermine biosynthesis contributes to plant resistance against V. dahliae through SA- and leucine-correlated signaling.
[Mh] Termos MeSH primário: Adenosilmetionina Descarboxilase/metabolismo
Gossypium/metabolismo
Gossypium/microbiologia
Espermina/biossíntese
Verticillium/patogenicidade
[Mh] Termos MeSH secundário: Adenosilmetionina Descarboxilase/genética
Arabidopsis/genética
Arabidopsis/microbiologia
Resistência à Doença/genética
Regulação da Expressão Gênica de Plantas
Leucina/metabolismo
Doenças das Plantas/microbiologia
Proteínas de Plantas/genética
Proteínas de Plantas/metabolismo
Plantas Geneticamente Modificadas
Putrescina/metabolismo
Ácido Salicílico/metabolismo
Espermina/metabolismo
Espermina Sintase/genética
Espermina Sintase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Plant Proteins); 2FZ7Y3VOQX (Spermine); EC 2.5.1.22 (Spermine Synthase); EC 4.1.1.50 (Adenosylmethionine Decarboxylase); GMW67QNF9C (Leucine); O414PZ4LPZ (Salicylic Acid); V10TVZ52E4 (Putrescine)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160114
[St] Status:MEDLINE
[do] DOI:10.1007/s00425-015-2463-5


  10 / 983 MEDLINE  
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[PMID]:26277788
[Au] Autor:Gupta ED; Pachauri M; Ghosh PC; Rajam MV
[Ad] Endereço:Department of Genetics, University of Delhi South Campus, Benito Juarez Road, New Delhi, 110021, India.
[Ti] Título:Targeting polyamine biosynthetic pathway through RNAi causes the abrogation of MCF 7 breast cancer cell line.
[So] Source:Tumour Biol;37(1):1159-71, 2016 Jan.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The diamine putrescine and polyamines, spermidine (triamine) and spermine (tetraamine) are small organic polycations that play an indispensable role in key cellular processes such as the regulation of growth, differentiation, and macromolecular functions. Elevated levels of polyamines (PAs) have been shown to be one of the major factors involved in carcinogenesis. In this study, specific silencing of the expression of three genes of PA biosynthesis pathway, ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase (SAMDC), and spermidine synthase (SPDSYN) was achieved using RNA interference in MCF 7 breast cancer cell line. For optimizing the effective small interfering nucleic acid (siNA), three variants of ODC siNA [siRNA, locked nucleic acid (LNA)-modified siRNA, and siHybrid (RNA and DNA hybrid)] were used and a dose- and time-dependent study was conducted. The PA biosynthetic genes were targeted individually and in combination. RNAi-mediated reduction in the expression of PA biosynthesis genes resulted in distorted cell morphology, reduced cancer cell viability, and migration characteristic. The most promising results were observed with the combined treatment of siSPDSYN and siODC with 83 % cell growth inhibition. On analyzing the messenger RNA (mRNA) expression profile of the cell cycle and apoptosis-related genes, it was observed that RNAi against PA biosynthetic genes downregulated the expression of CDK8, CCNE2, CCNH, CCNT1, CCNT2, CCNF, PCNA, CCND1, and CDK2, and upregulated the expression of E2F4, BAX, FAS, TP53, CDKN1A, BAK1, CDKN1B, ATM, GRANB, and ATR genes when compared with control-transfected cells. These results suggest that the targeting polyamine biosynthesis through RNAi approach could be a promising strategy for breast cancer therapy and might be extended for therapy of other cancers.
[Mh] Termos MeSH primário: Neoplasias da Mama/metabolismo
Poliaminas/química
Interferência de RNA
[Mh] Termos MeSH secundário: Adenosilmetionina Descarboxilase/metabolismo
Apoptose
Neoplasias da Mama/genética
Diferenciação Celular
Divisão Celular
Movimento Celular
Proliferação Celular
Sobrevivência Celular
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Células MCF-7
Ornitina Descarboxilase/metabolismo
Putrescina/biossíntese
RNA Mensageiro/metabolismo
RNA Interferente Pequeno/metabolismo
Espermidina/biossíntese
Espermidina Sintase/metabolismo
Espermina/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Polyamines); 0 (RNA, Messenger); 0 (RNA, Small Interfering); 2FZ7Y3VOQX (Spermine); EC 2.5.1.16 (Spermidine Synthase); EC 4.1.1.17 (Ornithine Decarboxylase); EC 4.1.1.50 (Adenosylmethionine Decarboxylase); U87FK77H25 (Spermidine); V10TVZ52E4 (Putrescine)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:171111
[Lr] Data última revisão:
171111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150817
[St] Status:MEDLINE
[do] DOI:10.1007/s13277-015-3912-2



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