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[PMID]:29248352
[Au] Autor:Li D; Luong TTM; Dan WJ; Ren Y; Nien HX; Zhang AL; Gao JM
[Ad] Endereço:Shaanxi Key Laboratory of Natural Products & Chemical Biology, Shaanxi Engineering Center of Bioresource Chemistry & Sustainable Utilization, College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, China.
[Ti] Título:Natural products as sources of new fungicides (IV): Synthesis and biological evaluation of isobutyrophenone analogs as potential inhibitors of class-II fructose-1,6-bisphosphate aldolase.
[So] Source:Bioorg Med Chem;26(2):386-393, 2018 01 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Several recently identified antifungal compounds share the backbone structure of acetophenones. The aim of the present study was to develop new isobutyrophenone analogs as new antifungal agents. A series of new 2,4-dihydroxy-5-methyl isobutyrophenone derivatives were prepared and characterized by H, C NMR and MS spectroscopic data. These products were evaluated for in vitro antifungal activities against seven plant fungal pathogens by the mycelial growth inhibitory rate assay. Compounds 3, 4a, 5a, 5b, 5e, 5f and 5g showed a broad-spectrum high antifungal activity. On the other hand, for the first time, these compounds were also assayed as potential inhibitors against Class II fructose-1,6-bisphosphate aldolase (Fba) from the rice blast fungus, Magnaporthe grisea. Compounds 5e and 5g were found to exhibit the inhibition constants (Ki) for 15.12 and 14.27 µM, respectively, as the strongest competitive inhibitors against Fba activity. The possible binding-modes of compounds 5e and 5g were further analyzed by molecular docking algorithms. The results strongly suggested that compound 5g could be a promising lead for the discovery of new fungicides via targeting Class II Fba.
[Mh] Termos MeSH primário: Antifúngicos/farmacologia
Produtos Biológicos/farmacologia
Butirofenonas/farmacologia
Inibidores Enzimáticos/farmacologia
Frutose-Bifosfato Aldolase/antagonistas & inibidores
Magnaporthe/efeitos dos fármacos
[Mh] Termos MeSH secundário: Antifúngicos/síntese química
Antifúngicos/química
Produtos Biológicos/síntese química
Produtos Biológicos/química
Butirofenonas/síntese química
Butirofenonas/química
Relação Dose-Resposta a Droga
Inibidores Enzimáticos/síntese química
Inibidores Enzimáticos/química
Frutose-Bifosfato Aldolase/metabolismo
Magnaporthe/enzimologia
Magnaporthe/crescimento & desenvolvimento
Testes de Sensibilidade Microbiana
Simulação de Acoplamento Molecular
Estrutura Molecular
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Biological Products); 0 (Butyrophenones); 0 (Enzyme Inhibitors); EC 4.1.2.13 (Fructose-Bisphosphate Aldolase)
[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:171218
[St] Status:MEDLINE


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[PMID]:28965950
[Au] Autor:Singh BP; Saha I; Nandi I; Swamy MJ
[Ad] Endereço:School of Chemistry, University of Hyderabad, Hyderabad, 500046, India.
[Ti] Título:Spermine and spermidine act as chemical chaperones and enhance chaperone-like and membranolytic activities of major bovine seminal plasma protein, PDC-109.
[So] Source:Biochem Biophys Res Commun;493(4):1418-1424, 2017 Dec 02.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The major bovine seminal plasma protein, PDC-109, binds to choline phospholipids of the sperm plasma membrane and induces an efflux of cholesterol and choline phospholipids (cholesterol efflux), which is crucial for sperm capacitation. PDC-109 also exhibits chaperone-like activity and protects target proteins against various kinds of stress. Here we show that the polyamines spermine and spermidine, present in high concentration in the seminal plasma of various mammals, increase the ability of PDC-109 to perturb membrane structure as well as its chaperone-like activity. Interestingly, spermine/spermidine alone did not perturb membrane structure but exhibited chaperone-like activity by protecting target proteins against thermal and oxidative stress. When spermine/spermidine was used along with PDC-109, the observed chaperone-like activity was considerably higher than that expected for a simple additive effect, suggesting that PDC-109 and the polyamines act in a synergistic fashion. These results indicate that at the high concentrations present in the seminal plasma spermine/spermidine exhibit a positive modulatory effect on the chaperone-like activity of PDC-109 and may also function as chemical chaperones and protect other seminal plasma proteins from various kinds of stress.
[Mh] Termos MeSH primário: Chaperonas Moleculares/metabolismo
Proteínas Secretadas pela Vesícula Seminal/metabolismo
Espermidina/metabolismo
Espermina/metabolismo
[Mh] Termos MeSH secundário: Animais
Bovinos
Membrana Celular/metabolismo
Membrana Eritrocítica/metabolismo
Frutose-Bifosfato Aldolase/antagonistas & inibidores
Frutose-Bifosfato Aldolase/química
Frutose-Bifosfato Aldolase/metabolismo
Temperatura Alta/efeitos adversos
Seres Humanos
Técnicas In Vitro
L-Lactato Desidrogenase/antagonistas & inibidores
L-Lactato Desidrogenase/química
L-Lactato Desidrogenase/metabolismo
Masculino
Lipídeos de Membrana/metabolismo
Membranas Artificiais
Chaperonas Moleculares/farmacologia
Estresse Oxidativo
Agregados Proteicos/efeitos dos fármacos
Desnaturação Proteica/efeitos dos fármacos
Sêmen/metabolismo
Espermidina/farmacologia
Espermina/farmacologia
Estresse Fisiológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Membrane Lipids); 0 (Membranes, Artificial); 0 (Molecular Chaperones); 0 (Protein Aggregates); 0 (Seminal Vesicle Secretory Proteins); 0 (seminal vesicle secretory protein 109, Bos taurus); 2FZ7Y3VOQX (Spermine); EC 1.1.1.27 (L-Lactate Dehydrogenase); EC 4.1.2.13 (Fructose-Bisphosphate Aldolase); U87FK77H25 (Spermidine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171003
[St] Status:MEDLINE


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[PMID]:28915239
[Au] Autor:Pinto J; Odongo S; Lee F; Gaspariunaite V; Muyldermans S; Magez S; Sterckx YG
[Ad] Endereço:Research Unit for Cellular and Molecular Immunology (CMIM), Vrije Universiteit Brussel (VUB), Brussels, Belgium.
[Ti] Título:Structural basis for the high specificity of a Trypanosoma congolense immunoassay targeting glycosomal aldolase.
[So] Source:PLoS Negl Trop Dis;11(9):e0005932, 2017 Sep.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Animal African trypanosomosis (AAT) is a neglected tropical disease which imposes a heavy burden on the livestock industry in Sub-Saharan Africa. Its causative agents are Trypanosoma parasites, with T. congolense and T. vivax being responsible for the majority of the cases. Recently, we identified a Nanobody (Nb474) that was employed to develop a homologous sandwich ELISA targeting T. congolense fructose-1,6-bisphosphate aldolase (TcoALD). Despite the high sequence identity between trypanosomatid aldolases, the Nb474-based immunoassay is highly specific for T. congolense detection. The results presented in this paper yield insights into the molecular principles underlying the assay's high specificity. METHODOLOGY/PRINCIPAL FINDINGS: The structure of the Nb474-TcoALD complex was determined via X-ray crystallography. Together with analytical gel filtration, the structure reveals that a single TcoALD tetramer contains four binding sites for Nb474. Through a comparison with the crystal structures of two other trypanosomatid aldolases, TcoALD residues Ala77 and Leu106 were identified as hot spots for specificity. Via ELISA and surface plasmon resonance (SPR), we demonstrate that mutation of these residues does not abolish TcoALD recognition by Nb474, but does lead to a lack of detection in the Nb474-based homologous sandwich immunoassay. CONCLUSIONS/SIGNIFICANCE: The results show that the high specificity of the Nb474-based immunoassay is not determined by the initial recognition event between Nb474 and TcoALD, but rather by its homologous sandwich design. This (i) provides insights into the optimal set-up of the assay, (ii) may be of great significance for field applications as it could explain the potential detection escape of certain T. congolense strains, and (iii) may be of general interest to those developing similar assays.
[Mh] Termos MeSH primário: Frutose-Bifosfato Aldolase/análise
Imunoensaio
Trypanosoma congolense/enzimologia
Trypanosoma congolense/imunologia
Tripanossomíase Africana/veterinária
Tripanossomíase Bovina/diagnóstico
[Mh] Termos MeSH secundário: África ao Sul do Saara/epidemiologia
Animais
Antígenos de Protozoários/análise
Antígenos de Protozoários/imunologia
Bovinos
Cristalografia por Raios X
Ensaio de Imunoadsorção Enzimática
Frutose-Bifosfato Aldolase/química
Frutose-Bifosfato Aldolase/genética
Frutose-Bifosfato Aldolase/imunologia
Mutagênese Sítio-Dirigida
Sensibilidade e Especificidade
Anticorpos de Domínio Único/química
Anticorpos de Domínio Único/imunologia
Trypanosoma congolense/química
Tripanossomíase Africana/diagnóstico
Tripanossomíase Africana/epidemiologia
Tripanossomíase Africana/parasitologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Protozoan); 0 (Single-Domain Antibodies); EC 4.1.2.13 (Fructose-Bisphosphate Aldolase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005932


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[PMID]:28816095
[Au] Autor:Halford J; Shen S; Itamura K; Levine J; Chong AC; Czerwieniec G; Glenn TC; Hovda DA; Vespa P; Bullock R; Dietrich WD; Mondello S; Loo JA; Wanner IB
[Ad] Endereço:1 Semel Institute for Neuroscience and Human Behavior, 12222 University of California , Los Angeles, CA, USA.
[Ti] Título:New astroglial injury-defined biomarkers for neurotrauma assessment.
[So] Source:J Cereb Blood Flow Metab;37(10):3278-3299, 2017 Oct.
[Is] ISSN:1559-7016
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Traumatic brain injury (TBI) is an expanding public health epidemic with pathophysiology that is difficult to diagnose and thus treat. TBI biomarkers should assess patients across severities and reveal pathophysiology, but currently, their kinetics and specificity are unclear. No single ideal TBI biomarker exists. We identified new candidates from a TBI CSF proteome by selecting trauma-released, astrocyte-enriched proteins including aldolase C (ALDOC), its 38kD breakdown product (BDP), brain lipid binding protein (BLBP), astrocytic phosphoprotein (PEA15), glutamine synthetase (GS) and new 18-25kD-GFAP-BDPs. Their levels increased over four orders of magnitude in severe TBI CSF. First post-injury week, ALDOC levels were markedly high and stable. Short-lived BLBP and PEA15 related to injury progression. ALDOC, BLBP and PEA15 appeared hyper-acutely and were similarly robust in severe and mild TBI blood; 25kD-GFAP-BDP appeared overnight after TBI and was rarely present after mild TBI. Using a human culture trauma model, we investigated biomarker kinetics. Wounded (mechanoporated) astrocytes released ALDOC, BLBP and PEA15 acutely. Delayed cell death corresponded with GFAP release and proteolysis into small GFAP-BDPs. Associating biomarkers with cellular injury stages produced astroglial injury-defined (AID) biomarkers that facilitate TBI assessment, as neurological deficits are rooted not only in death of CNS cells, but also in their functional compromise.
[Mh] Termos MeSH primário: Astrócitos/patologia
Biomarcadores/análise
Lesões Encefálicas Traumáticas/líquido cefalorraquidiano
[Mh] Termos MeSH secundário: Astrócitos/química
Concussão Encefálica
Lesões Encefálicas Traumáticas/diagnóstico
Células Cultivadas
Proteína 7 de Ligação a Ácidos Graxos/sangue
Frutose-Bifosfato Aldolase/sangue
Seres Humanos
Peptídeos e Proteínas de Sinalização Intracelular/sangue
Cinética
Fosfoproteínas/sangue
Proteoma/análise
Proteínas Supressoras de Tumor/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (FABP7 protein, human); 0 (Fatty Acid-Binding Protein 7); 0 (Intracellular Signaling Peptides and Proteins); 0 (PEA15 protein, human); 0 (Phosphoproteins); 0 (Proteome); 0 (Tumor Suppressor Proteins); EC 4.1.2.13 (Fructose-Bisphosphate Aldolase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE
[do] DOI:10.1177/0271678X17724681


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[PMID]:28610954
[Au] Autor:Chang YC; Chan YC; Chang WM; Lin YF; Yang CJ; Su CY; Huang MS; Wu ATH; Hsiao M
[Ad] Endereço:Graduate Institute of Life Sciences, National Defense Medical Center, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
[Ti] Título:Feedback regulation of ALDOA activates the HIF-1α/MMP9 axis to promote lung cancer progression.
[So] Source:Cancer Lett;403:28-36, 2017 Sep 10.
[Is] ISSN:1872-7980
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Distant metastasis and recurrence are the greatest challenges in the clinical management of lung cancer. Despite advances in targeted therapies, high mortality rates persist. Therefore, alternative therapeutic interventions are urgently required. Accumulating evidence indicates that normalizing tumor metabolism may be a way to increase therapeutic efficacy and to reduce tumor malignancy. Here, we analyzed integrated transcriptomics data and an shRNA library against glycolytic enzymes and found that elevated Aldolase A expression is highly correlated with metastatic potential and a poor prognosis in patients with non-small cell lung cancer (NSCLC). We validated our in silico findings with an immunohistochemical analysis of clinical samples. Aldolase A silencing significantly suppressed metastatic potential both in vitro and in vivo, whereas the ectopic overexpression of Aldolase A resulted in the opposite phenotype. Furthermore, our microarray and Ingenuity Pathway Analyses (IPA) revealed that Aldolase A-driven lung cancer metastasis was closely linked to hypoxia inducible factor 1 alpha (HIF-1α)-downstream signaling. Importantly, Aldolase A overexpression may promote the release of lactate to block PHD activities and further induce HIF-1α stabilization. Aldolase A and nuclear HIF-1α overexpression levels were positively correlated and were significantly associated with a poorer survival rate in lung cancer patients (P = 0.008 for Overall Survival, P = 0.021 for Disease-free Survival). Furthermore, MMP9, a downstream target of HIF-1α, was significantly upregulated after ALDOA overexpression. A MMP9 inhibitor significantly inhibited cell invasion and migration in ALDOA-HIF-1α axis-induced lung cancer. In summary, our results reveal the molecular mechanism of Aldolase A in promoting lung cancer metastasis via PHD-mediated stabilization of HIF-1α and the subsequent activation of MMP9. The ALDOA-HIF-1α axis may provide a new therapeutic target for metastatic lung cancer treatment.
[Mh] Termos MeSH primário: Carcinoma Pulmonar de Células não Pequenas/enzimologia
Movimento Celular
Frutose-Bifosfato Aldolase/metabolismo
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Neoplasias Pulmonares/enzimologia
Metaloproteinase 9 da Matriz/metabolismo
[Mh] Termos MeSH secundário: Idoso
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
Carcinoma Pulmonar de Células não Pequenas/genética
Carcinoma Pulmonar de Células não Pequenas/patologia
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Progressão da Doença
Intervalo Livre de Doença
Ativação Enzimática
Feminino
Frutose-Bifosfato Aldolase/genética
Perfilação da Expressão Gênica/métodos
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Hidroxilação
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética
Estimativa de Kaplan-Meier
Neoplasias Pulmonares/tratamento farmacológico
Neoplasias Pulmonares/genética
Neoplasias Pulmonares/patologia
Masculino
Inibidores de Metaloproteinases de Matriz/farmacologia
Meia-Idade
Invasividade Neoplásica
Prolil Hidroxilases/metabolismo
Modelos de Riscos Proporcionais
Estabilidade Proteica
Proteólise
Interferência de RNA
Estudos Retrospectivos
Transdução de Sinais
Fatores de Tempo
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HIF1A protein, human); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (Matrix Metalloproteinase Inhibitors); EC 1.14.11.- (Prolyl Hydroxylases); EC 3.4.24.35 (MMP9 protein, human); EC 3.4.24.35 (Matrix Metalloproteinase 9); EC 4.1.2.13 (ALDOA protein, human); EC 4.1.2.13 (Fructose-Bisphosphate Aldolase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170615
[St] Status:MEDLINE


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[PMID]:28558381
[Au] Autor:Li Q; Li Y; Xu J; Wang S; Xu Y; Li X; Cai S
[Ad] Endereço:Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
[Ti] Título:Aldolase B Overexpression is Associated with Poor Prognosis and Promotes Tumor Progression by Epithelial-Mesenchymal Transition in Colorectal Adenocarcinoma.
[So] Source:Cell Physiol Biochem;42(1):397-406, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Glycolysis is considered to be the root of cancer development and progression, which involved a multi-step enzymatic reaction. Our study aimed at figuring out which glycolysis enzyme participates in the development of colorectal cancer and its possible mechanisms. METHODS: We firstly screened out Aldolase B (ALDOB) by performing qRT-PCR arrays of glycolysis-related genes in five paired liver metastasis and primary colorectal tissues, and further detected ALDOB protein with immunohistochemistry in tissue microarray (TMA) consisting of 229 samples from stage I-III colorectal cancer patients. CRISPR-Cas9 method was adopted to create knock out colon cancer cell lines (LoVo and SW480) of ALDOB. The effect of ALDOB on cell proliferation and metastasis was examined in vitro using colony formation assay as well as transwell migration and invasion assay, respectively. RESULTS: In TMA, there was 64.6% of samples demonstrated strong intensity of ALDOB. High ALDOB expression were associated with poor overall survival and disease-free survival in both univariate and multivariate regression analyses (P<0.05). In vitro functional studies of CCK-8 demonstrated that silencing ALDOB expression significantly (P<0.05) inhibited proliferation, migration and invasion of colon cancer cells. Mechanically, silencing ALDOB activated epithelial markers and repressed mesenchymal markers, indicating inactivation of ALDOB may lead to inhibition of epithelial-mesenchymal transition (EMT). CONCLUSION: Upregulation of ALDOB promotes colorectal cancer metastasis by facilitating EMT and acts as a potential prognostic factor and therapeutic target in colorectal cancer.
[Mh] Termos MeSH primário: Adenocarcinoma/diagnóstico
Neoplasias Colorretais/diagnóstico
Transição Epitelial-Mesenquimal
Frutose-Bifosfato Aldolase/metabolismo
[Mh] Termos MeSH secundário: Adenocarcinoma/mortalidade
Adenocarcinoma/patologia
Idoso
Sistemas CRISPR-Cas/genética
Linhagem Celular Tumoral
Movimento Celular
Proliferação Celular
Neoplasias Colorretais/mortalidade
Neoplasias Colorretais/patologia
Intervalo Livre de Doença
Feminino
Frutose-Bifosfato Aldolase/antagonistas & inibidores
Frutose-Bifosfato Aldolase/genética
Glicólise
Seres Humanos
Neoplasias Hepáticas/patologia
Neoplasias Hepáticas/secundário
Masculino
Meia-Idade
Estadiamento de Neoplasias
Prognóstico
Interferência de RNA
Vimentina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Vimentin); EC 4.1.2.13 (Fructose-Bisphosphate Aldolase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170531
[St] Status:MEDLINE
[do] DOI:10.1159/000477484


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[PMID]:28552792
[Au] Autor:Krause RGE; Hurdayal R; Choveaux D; Przyborski JM; Coetzer THT; Goldring JPD
[Ad] Endereço:Biochemistry, University of KwaZulu-Natal, P.B. X01, Carbis Road, Scottsville 3209, South Africa.
[Ti] Título:Plasmodium glyceraldehyde-3-phosphate dehydrogenase: A potential malaria diagnostic target.
[So] Source:Exp Parasitol;179:7-19, 2017 Aug.
[Is] ISSN:1090-2449
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Malaria rapid diagnostic tests (RDTs) are immunochromatographic tests detecting Plasmodial histidine-rich protein 2 (HRP2), lactate dehydrogenase (LDH) and aldolase. HRP2 is only expressed by Plasmodium falciparum parasites and the protein is not expressed in several geographic isolates. LDH-based tests lack sensitivity compared to HRP2 tests. This study explored the potential of the Plasmodial glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), as a new malaria diagnostic biomarker. The P. falciparum and P. yoelii proteins were recombinantly expressed in BL21(DE3) Escherischia coli host cells and affinity purified. Two epitopes (CADGFLLIGEKKVSVFA and CAEKDPSQIPWGKCQV) specific to P. falciparum GAPDH and one common to all mammalian malaria species (CKDDTPIYVMGINH) were identified. Antibodies were raised in chickens against the two recombinant proteins and the three epitopes and affinity purified. The antibodies detected the native protein in parasite lysates as a 38 kDa protein and immunofluorescence verified a parasite cytosolic localization for the native protein. The antibodies suggested a 4-6 fold higher concentration of native PfGAPDH compared to PfLDH in immunoprecipitation and ELISA formats, consistent with published proteomic data. PfGAPDH shows interesting potential as a malaria diagnostic biomarker.
[Mh] Termos MeSH primário: Anticorpos Antiprotozoários/imunologia
Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/metabolismo
Malária Falciparum/diagnóstico
Plasmodium falciparum/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Anticorpos Antiprotozoários/biossíntese
Especificidade de Anticorpos
Antígenos de Protozoários/isolamento & purificação
Biomarcadores/análise
Western Blotting
Galinhas
Cromatografia em Gel
Diagnóstico Diferencial
Ensaio de Imunoadsorção Enzimática
Epitopos/imunologia
Epitopos/isolamento & purificação
Imunofluorescência
Frutose-Bifosfato Aldolase/isolamento & purificação
Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/química
Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/imunologia
Imunocromatografia
Imunoglobulina G/biossíntese
Imunoglobulina G/imunologia
Imunoglobulina G/isolamento & purificação
Imunoglobulinas/imunologia
Imunoprecipitação
L-Lactato Desidrogenase/imunologia
L-Lactato Desidrogenase/isolamento & purificação
L-Lactato Desidrogenase/metabolismo
Plasmodium falciparum/imunologia
Plasmodium yoelii/enzimologia
Plasmodium yoelii/imunologia
Proteínas de Protozoários/isolamento & purificação
Coelhos
Proteínas Recombinantes/imunologia
Proteínas Recombinantes/isolamento & purificação
Proteínas Recombinantes/metabolismo
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Protozoan); 0 (Antigens, Protozoan); 0 (Biomarkers); 0 (Epitopes); 0 (HRP-2 antigen, Plasmodium falciparum); 0 (IgY); 0 (Immunoglobulin G); 0 (Immunoglobulins); 0 (Protozoan Proteins); 0 (Recombinant Proteins); EC 1.1.1.27 (L-Lactate Dehydrogenase); EC 1.2.1.12 (Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)); EC 4.1.2.13 (Fructose-Bisphosphate Aldolase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170726
[Lr] Data última revisão:
170726
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170530
[St] Status:MEDLINE


  8 / 5347 MEDLINE  
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[PMID]:28475320
[Au] Autor:Han X; Zhu X; Hong Z; Wei L; Ren Y; Wan F; Zhu S; Peng H; Guo L; Rao L; Feng L; Wan J
[Ad] Endereço:International Cooperation Base of Pesticide and Green Synthesis (Hubei), Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University , Wuhan 430079, China.
[Ti] Título:Structure-Based Rational Design of Novel Inhibitors Against Fructose-1,6-Bisphosphate Aldolase from Candida albicans.
[So] Source:J Chem Inf Model;57(6):1426-1438, 2017 Jun 26.
[Is] ISSN:1549-960X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Class II fructose-1,6-bisphosphate aldolases (FBA-II) are attractive new targets for the discovery of drugs to combat invasive fungal infection, because they are absent in animals and higher plants. Although several FBA-II inhibitors have been reported, none of these inhibitors exhibit antifungal effect so far. In this study, several novel inhibitors of FBA-II from C. albicans (Ca-FBA-II) with potent antifungal effects were rationally designed by jointly using a specific protocols of molecular docking-based virtual screening, accurate binding-conformation evaluation strategy, synthesis and enzymatic assays. The enzymatic assays reveal that the compounds 3c, 3e-g, 3j and 3k exhibit high inhibitory activity against Ca-FBA-II (IC < 10 µM), and the most potential inhibitor is 3g, with IC value of 2.7 µM. Importantly, the compounds 3f, 3g, and 3l possess not only high inhibitions against Ca-FBA-II, but also moderate antifungal activities against C. glabrata (MIC = 4-64 µg/mL). The compounds 3g, 3l, and 3k in combination with fluconazole (8 µg/mL) displayed significantly synergistic antifungal activities (MIC < 0.0625 µg/mL) against resistant Candida strains, which are resistant to azoles drugs. The probable binding modes between 3g and the active site of Ca-FBA-II have been proposed by using the DOX (docking, ONIOM, and XO) strategy. To our knowledge, no FBA-II inhibitors with antifungal activities against wild type and resistant strains from Candida were reported previously. The positive results suggest that the strategy adopted in this study are a promising method for the discovery of novel drugs against azole-resistant fungal pathogens in the future.
[Mh] Termos MeSH primário: Antifúngicos/química
Antifúngicos/farmacologia
Candida albicans/enzimologia
Desenho de Drogas
Inibidores Enzimáticos/química
Inibidores Enzimáticos/farmacologia
Frutose-Bifosfato Aldolase/antagonistas & inibidores
[Mh] Termos MeSH secundário: Candida albicans/efeitos dos fármacos
Frutose-Bifosfato Aldolase/química
Frutose-Bifosfato Aldolase/metabolismo
Frutosedifosfatos/metabolismo
Testes de Sensibilidade Microbiana
Simulação de Dinâmica Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Enzyme Inhibitors); 0 (Fructosediphosphates); EC 4.1.2.13 (Fructose-Bisphosphate Aldolase); M7522JYX1H (fructose-1,6-diphosphate)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170921
[Lr] Data última revisão:
170921
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170506
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jcim.6b00763


  9 / 5347 MEDLINE  
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[PMID]:28426139
[Au] Autor:Rahimi M; van der Meer JY; Geertsema EM; Poelarends GJ
[Ad] Endereço:Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
[Ti] Título:Engineering a Promiscuous Tautomerase into a More Efficient Aldolase for Self-Condensations of Linear Aliphatic Aldehydes.
[So] Source:Chembiochem;18(14):1435-1441, 2017 Jul 18.
[Is] ISSN:1439-7633
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The enzyme 4-oxalocrotonate tautomerase (4-OT) from Pseudomonas putida mt-2 takes part in a catabolic pathway for aromatic hydrocarbons, where it catalyzes the conversion of 2hydroxyhexa-2,4-dienedioate into 2-oxohexa-3-enedioate. This tautomerase can also promiscuously catalyze carbon-carbon bond-forming reactions, including various types of aldol reactions, by using its amino-terminal proline as a key catalytic residue. Here, we used systematic mutagenesis to identify two hotspots in 4-OT (Met45 and Phe50) at which single mutations give marked improvements in aldolase activity for the self-condensation of propanal. Activity screening of a focused library in which these two hotspots were varied led to the discovery of a 4-OT variant (M45Y/F50V) with strongly enhanced aldolase activity in the self-condensation of linear aliphatic aldehydes, such as acetaldehyde, propanal, and butanal, to yield α,ß-unsaturated aldehydes. With both propanal and benzaldehyde, this double mutant, unlike the previously constructed single mutant F50A, mainly catalyzes the self-condensation of propanal rather than the cross-condensation of propanal and benzaldehyde, thus indicating that it indeed has altered substrate specificity. This variant could serve as a template to create new biocatalysts that lack dehydration activity and possess further enhanced aldolase activity, thus enabling the efficient enzymatic self-coupling of aliphatic aldehydes.
[Mh] Termos MeSH primário: Aldeídos/metabolismo
Frutose-Bifosfato Aldolase/metabolismo
Isomerases/metabolismo
Engenharia de Proteínas
Pseudomonas putida/enzimologia
[Mh] Termos MeSH secundário: Aldeídos/química
Frutose-Bifosfato Aldolase/química
Frutose-Bifosfato Aldolase/genética
Isomerases/química
Isomerases/genética
Estrutura Molecular
Pseudomonas putida/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aldehydes); EC 4.1.2.13 (Fructose-Bisphosphate Aldolase); EC 5.- (4-oxalocrotonate tautomerase); EC 5.- (Isomerases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170421
[St] Status:MEDLINE
[do] DOI:10.1002/cbic.201700121


  10 / 5347 MEDLINE  
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[PMID]:28403889
[Au] Autor:Abdul-Aziz R; Yu CY; Adler B; Bout-Tabaku S; Lintner KE; Moore-Clingenpeel M; Spencer CH
[Ad] Endereço:Nationwide Children's Hospital, 700 Children's Dr, Columbus, OH, 43205, USA. raziz@upa.chob.edu.
[Ti] Título:Muscle MRI at the time of questionable disease flares in Juvenile Dermatomyositis (JDM).
[So] Source:Pediatr Rheumatol Online J;15(1):25, 2017 Apr 12.
[Is] ISSN:1546-0096
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The course of JDM has improved substantially over the last 70 years with early and aggressive treatments. Yet it remains difficult to detect disease flares as symptoms may be mild; signs of rash and muscle weakness vary widely and are often equivocal; laboratory tests of muscle enzyme levels are often normal; electromyography and muscle biopsy are invasive. Alternative tools are needed to help decide if more aggressive treatment is needed. Our objective is to determine the effectiveness of muscle Magnetic Resonance Imaging (MRI) in detecting JDM flares, and how an MRI affects physician's decision-making regarding treatment. METHODS: This study was approved by the Institutional Review Board of Nationwide Children's Hospital. JDM patients were consulted between 1/2005 and 6/2015. MRIs were performed on both lower extremities without contrast sequentially: axial T1, axial T2 fat saturation, axial and coronal inversion recovery, and axial diffusion weighted. The physician decision that a JDM patient was in a flare was considered the gold standard. MRI results were compared with physician's decisions on whether a relapse had occurred, and if there was a concordance between the assessment methods. RESULTS: Forty-five JDM patients were studied. Eighty percent had weakness at diagnosis, 100% typical rash, and 73% typical nail-fold capillary changes. At diagnosis, muscle enzymes were compatible with JDM generally (CK 52%, LDH 62%, aldolase 72%, AST 54% abnormal). EMG was abnormal in 3/8, muscle biopsy typical of JDM in 10/11, and MRI abnormal demonstrating myositis in 31/40. Thirteen patients had a repeat MRI for possible flares with differing indications. Three repeat MRI's were abnormal, demonstrating myositis. There was moderate agreement about flares between MRI findings and physician's treatment decisions (kappa = 0.59). In each abnormal MRI case the physician decided to increase treatment (100% probability for flares). MRI was negative for myositis in 10 patients, by which 7/10 the physicians chose to continue or to taper the medications (70% probability for non-flares). CONCLUSION: A muscle MRI would facilitate objective assessments of JDM flares. When an MRI shows myositis, physicians tend to treat 100% of the time. When an MRI shows no myositis, physicians continued the same medications or tapered medications 70% of the time. Further studies would help confirm the utility and cost-effectiveness of MRI to determine JDM flares.
[Mh] Termos MeSH primário: Dermatomiosite/diagnóstico por imagem
Músculo Esquelético/diagnóstico por imagem
[Mh] Termos MeSH secundário: Adolescente
Aspartato Aminotransferases/sangue
Criança
Pré-Escolar
Creatina Quinase/sangue
Dermatomiosite/sangue
Dermatomiosite/complicações
Dermatomiosite/fisiopatologia
Progressão da Doença
Eletromiografia
Exantema/etiologia
Exantema/fisiopatologia
Feminino
Frutose-Bifosfato Aldolase/sangue
Seres Humanos
Lactente
L-Lactato Desidrogenase/sangue
Extremidade Inferior/diagnóstico por imagem
Imagem por Ressonância Magnética
Masculino
Angioscopia Microscópica
Debilidade Muscular/etiologia
Debilidade Muscular/fisiopatologia
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 1.1.1.27 (L-Lactate Dehydrogenase); EC 2.6.1.1 (Aspartate Aminotransferases); EC 2.7.3.2 (Creatine Kinase); EC 4.1.2.13 (Fructose-Bisphosphate Aldolase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170414
[St] Status:MEDLINE
[do] DOI:10.1186/s12969-017-0154-4



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