Base de dados : MEDLINE
Pesquisa : D08.811.399.894 [Categoria DeCS]
Referências encontradas : 1189 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 119 ir para página                         

  1 / 1189 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28744579
[Au] Autor:Uda K; Abe K; Dehara Y; Mizobata K; Edashige Y; Nishimura R; Radkov AD; Moe LA
[Ad] Endereço:Laboratory of Biochemistry, Faculty of Science and Technology, Kochi University, Kochi, 780-8520, Japan. k-uda@kochi-u.ac.jp.
[Ti] Título:Triple serine loop region regulates the aspartate racemase activity of the serine/aspartate racemase family.
[So] Source:Amino Acids;49(10):1743-1754, 2017 10.
[Is] ISSN:1438-2199
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:Recently, we cloned and characterized eleven serine and aspartate racemases (SerR and AspR, respectively) from animals. These SerRs and AspRs are not separated by their racemase functions and form a serine/aspartate racemase family cluster based on phylogenetic analysis. Moreover, we have proposed that the AspR-specific triple serine loop region at amino acid positions 150-152 may be responsible for the large AspR activity. In the present study, to test this hypothesis, we prepared and characterized fourteen mutants in this region of animal SerRs and AspRs. The large AspR activity in Acropora and Crassostrea AspR was reduced to <0.04% of wild-type after substitution of the triple serine loop region. Conversely, introducing the triple serine loop region into Acropora, Crassostrea, and Penaeus SerR drastically increased the AspR activity. Those mutants showed similar or higher substrate affinity for aspartate than serine and showed 11-683-fold higher k and 28-351-fold higher k /K values for aspartate than serine racemization. Furthermore, we introduced serine residues in all combinations at position 150-152 in mouse SerR. These mutants revealed that a change in the enzyme function from SerR to AspR can be caused by introduction of Ser151 and Ser152, and addition of the third serine residue at position 150 further enhances the enzyme specificity for aspartate due to a decrease in the serine racemase and serine dehydratase activity. Here, we provide convincing evidence that the AspR gene has evolved from the SerR gene by acquisition of the triple serine loop region.
[Mh] Termos MeSH primário: Isomerases de Aminoácido
Antozoários
Proteínas de Artrópodes
Crassostrea
Mutação de Sentido Incorreto
Penaeidae
Racemases e Epimerases
[Mh] Termos MeSH secundário: Isomerases de Aminoácido/química
Isomerases de Aminoácido/genética
Substituição de Aminoácidos
Animais
Antozoários/enzimologia
Antozoários/genética
Proteínas de Artrópodes/química
Proteínas de Artrópodes/genética
Crassostrea/enzimologia
Crassostrea/genética
Camundongos
Penaeidae/enzimologia
Penaeidae/genética
Estrutura Secundária de Proteína
Racemases e Epimerases/química
Racemases e Epimerases/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Arthropod Proteins); EC 5.1.- (Racemases and Epimerases); EC 5.1.1.- (Amino Acid Isomerases); EC 5.1.1.13 (aspartate racemase); EC 5.1.1.16 (serine racemase)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1007/s00726-017-2472-8


  2 / 1189 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29304076
[Au] Autor:Ozaki H; Inoue R; Matsushima T; Sasahara M; Hayashi A; Mori H
[Ad] Endereço:Department of Molecular Neuroscience, Graduate School of Innovative Life Science, University of Toyama, Toyama, Japan.
[Ti] Título:Serine racemase deletion attenuates neurodegeneration and microvascular damage in diabetic retinopathy.
[So] Source:PLoS One;13(1):e0190864, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Diabetic retinopathy (DR) is a leading cause of blindness. DR is recognized as a microvascular disease and inner retinal neurodegeneration. In the course of retinal neurodegeneration, N-methyl-D-aspartate receptor (NMDAR)-mediated excitotoxicity is involved. Full activation of NMDAR requires binding of agonist glutamate and coagonist glycine or D-serine. D-Serine is produced from L-serine by serine racemase (SRR) and contributes to retinal neurodegeneration in rodent models of DR. However, the involvement of SRR in both neurodegeneration and microvascular damage in DR remains unclear. Here, we established diabetic model of SRR knockout (SRR-KO) and control wild-type (WT) mice by streptozotocin injection. Six months after the onset of diabetes, the number of survived retinal ganglion cells was higher in SRR-KO mice than that of WT mice. The reduction of thickness of inner retinal layer (IRL) was attenuated in SRR-KO mice than that of WT mice. Moreover, the number of damaged acellular capillaries was lower in SRR-KO mice than that of WT mice. Our results suggest the suppression of SRR activity may have protective effects in DR.
[Mh] Termos MeSH primário: Retinopatia Diabética/patologia
Microvasos/patologia
Neurônios/patologia
Racemases e Epimerases/genética
[Mh] Termos MeSH secundário: Animais
Retinopatia Diabética/enzimologia
Camundongos
Camundongos Knockout
Estreptozocina
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
5W494URQ81 (Streptozocin); EC 5.1.- (Racemases and Epimerases); EC 5.1.1.16 (serine racemase)
[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:180106
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190864


  3 / 1189 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29277318
[Au] Autor:Eryilmaz IE; Kordan Y; Vuruskan BA; Kaygisiz O; Tunca B; Cecener G
[Ad] Endereço:Uludag University, Faculty of Medicine, Medical Biology Department, Gorukle, Bursa, Turkey.
[Ti] Título:T2E (TMPRSS2-ERG) fusion transcripts are associated with higher levels of AMACR mRNA and a subsequent prostate cancer diagnosis in patients with atypical small acinar proliferation.
[So] Source:Gene;645:69-75, 2018 Mar 01.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Genetic rearrangements involving androgen-regulated transmembrane protease serine 2 (TMPRSS2) and genes from the ETS transcription factor family, most commonly ERG and ETV1, result in alteration that responsible for oncogenic activity in prostate cancer (PC). The aims of the present study were to: 1) investigate the frequency of these fusion transcripts in prostate tissue samples obtained from patients diagnosed with atypical small acinar proliferation (ASAP), 2) determine any clinical significance of T2E expression at the RNA level in predicting PC detection in subsequent biopsies, and 3) evaluate expression of the PC marker, alpha-methylacyl-CoA racemase (AMACR), according to T2E status by real-time quantitative reverse transcription PCR (RT-qPCR). T2E transcripts were detected in 31.7% (n=20) of the patients examined, and this was significantly associated with subsequent detection of PC in ASAP patients with a prostate specific antigen (PSA) level of 4-10ng/ml (p=0.045). AMACR expression was also significantly higher in the patients who were diagnosed with PC in subsequent biopsies than in the patients who were not diagnosed with PC (p=0.034) and in T2E-positive ASAP patients (p=0.002) compared to T2E-negative ASAP patients. Although these results need to be further clinically validated, we suggest that the presence of T2E transcript, in association with higher AMACR expression, is an indicator of PC risk from a T2E-positive focus or an unsampled malignant gland adjacent to a T2E-positive site in ASAP lesions.
[Mh] Termos MeSH primário: Células Acinares/patologia
Proteínas de Fusão Oncogênicas/genética
Neoplasias da Próstata/diagnóstico
Racemases e Epimerases/genética
[Mh] Termos MeSH secundário: Idoso
Biópsia
Detecção Precoce de Câncer
Predisposição Genética para Doença
Seres Humanos
Masculino
Meia-Idade
Neoplasias da Próstata/genética
Estudos Retrospectivos
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Oncogene Proteins, Fusion); 0 (TMPRSS2-ERG fusion protein, human); EC 5.1.- (Racemases and Epimerases); EC 5.1.99.4 (alpha-methylacyl-CoA racemase)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171227
[St] Status:MEDLINE


  4 / 1189 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28923398
[Au] Autor:Sun LN; Zhi Z; Chen LY; Zhou Q; Li XM; Gan WJ; Chen S; Yang M; Liu Y; Shen T; Xu Y; Li JM
[Ad] Endereço:Department of Pathology and Pathophysiology, Medical College of Soochow University, Soochow University, Suzhou 215123, People's Republic of China.
[Ti] Título:SIRT1 suppresses colorectal cancer metastasis by transcriptional repression of miR-15b-5p.
[So] Source:Cancer Lett;409:104-115, 2017 Nov 28.
[Is] ISSN:1872-7980
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:The class III deacetylase sirtuin 1 (SIRT1), a member of the sirtuin family proteins, plays a key role in many types of cancers including colorectal cancer (CRC). Here we report that SIRT1 suppressed CRC metastasis in vitro and in vivo as a negative regulator for miR-15b-5p transcription. Mechanistically, SIRT1 impaired regulatory effects of activator protein (AP-1) on miR-15b-5p trans-activation through deacetylation of AP-1. Importantly, acyl-CoA oxidase 1 (ACOX1), a key enzyme of the fatty acid oxidation (FAO) pathway, was found as a direct target for miR-15b-5p. SIRT1 expression was positively correlated with ACOX1 expression in CRC cells and in xenografts. Moreover, ACOX1 overexpression attenuated the augmentation of migration and invasion of CRC cells by miR-15b-5p overexpression. In conclusion, our study demonstrated a functional role of the SIRT1/miR-15b-5p/ACOX1 axis in CRC metastasis and suggested a potential target for metastatic CRC therapy.
[Mh] Termos MeSH primário: Neoplasias Colorretais/genética
MicroRNAs/genética
Sirtuína 1/genética
[Mh] Termos MeSH secundário: 3-Hidroxiacil-CoA Desidrogenases/metabolismo
Acetil-CoA C-Aciltransferase/metabolismo
Animais
Células CACO-2
Isomerases de Ligação Dupla Carbono-Carbono/metabolismo
Linhagem Celular Tumoral
Neoplasias Colorretais/metabolismo
Neoplasias Colorretais/patologia
Enoil-CoA Hidratase/metabolismo
Células HCT116
Células HT29
Xenoenxertos
Seres Humanos
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
MicroRNAs/metabolismo
Metástase Neoplásica
Racemases e Epimerases/metabolismo
Transdução de Sinais
Sirtuína 1/metabolismo
Transcrição Genética
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MIRN15 microRNA, human); 0 (MicroRNAs); 0 (fatty acid oxidation complex); EC 1.1.1.- (3-Hydroxyacyl CoA Dehydrogenases); EC 2.3.1.16 (Acetyl-CoA C-Acyltransferase); EC 3.5.1.- (SIRT1 protein, human); EC 3.5.1.- (Sirtuin 1); EC 4.2.1.17 (Enoyl-CoA Hydratase); EC 5.1.- (Racemases and Epimerases); EC 5.3.3.- (Carbon-Carbon Double Bond Isomerases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE


  5 / 1189 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28892569
[Au] Autor:Jiang H; Wu M; Liu Y; Song L; Li S; Wang X; Zhang YF; Fang J; Wu S
[Ad] Endereço:School of Optometry and Ophthalmolgy and the Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
[Ti] Título:Serine racemase deficiency attenuates choroidal neovascularization and reduces nitric oxide and VEGF levels by retinal pigment epithelial cells.
[So] Source:J Neurochem;143(3):375-388, 2017 Nov.
[Is] ISSN:1471-4159
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Choroidal neovascularization (CNV) is a leading cause of blindness in age-related macular degeneration. Production of vascular endothelial growth factor (VEGF) and macrophage recruitment by retinal pigment epithelial cells (RPE) significantly contributes to the process of CNV in an experimental CNV model. Serine racemase (SR) is expressed in retinal neurons and glial cells, and its product, d-serine, is an endogenous co-agonist of N-methyl-d-aspartate receptor. Activation of the receptor results in production of nitric oxide ( NO), a molecule that promotes retinal and choroidal neovascularization. These observations suggest possible roles of SR in CNV. With laser-injured CNV mice, we found that inactivation of SR-coding gene (Srr ) significantly reduced CNV volume, neovascular density, and invading macrophages. We exploited the underlying mechanism in vivo and ex vivo. RPE from wild-type (WT) mice expressed SR. To explore the possible downstream target of SR inactivation, we showed that choroid/RPE homogenates extracted from laser-injured Srr mice contained less inducible nitric oxide synthase and decreased phospho-VEGFR2 compared to amounts in WT mice. In vitro, inflammation-primed WT RPEs expressed more inducible NOS, produced more NO and VEGF than did inflammation-primed Srr RPEs. When co-cultured with inflammation-primed Srr RPE, significantly fewer RF/6A-a cell line of choroidal endothelial cell, migrated to the opposite side of the insert membrane than did cells co-cultured with pre-treated WT RPE. Altogether, SR deficiency reduces RPE response to laser-induced inflammatory stimuli, resulting in decreased production of a cascade of pro-angiogenic cytokines, including NO and VEGF, and reduced macrophage recruitment, which contribute synergistically to attenuated angiogenesis.
[Mh] Termos MeSH primário: Cegueira/patologia
Neovascularização de Coroide/genética
Regulação da Expressão Gênica/genética
Óxido Nítrico/metabolismo
Racemases e Epimerases/deficiência
Epitélio Pigmentado da Retina/metabolismo
Fator A de Crescimento do Endotélio Vascular/metabolismo
[Mh] Termos MeSH secundário: Animais
Cegueira/etiologia
Cegueira/genética
Células Cultivadas
Neovascularização de Coroide/patologia
Citocinas/metabolismo
Modelos Animais de Doenças
Regulação da Expressão Gênica/efeitos da radiação
Lasers/efeitos adversos
Lipopolissacarídeos/farmacologia
Macrófagos/fisiologia
Macrófagos/efeitos da radiação
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Mutação/genética
RNA Mensageiro/metabolismo
Racemases e Epimerases/genética
Epitélio Pigmentado da Retina/efeitos dos fármacos
Serina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Lipopolysaccharides); 0 (RNA, Messenger); 0 (Vascular Endothelial Growth Factor A); 31C4KY9ESH (Nitric Oxide); 452VLY9402 (Serine); EC 5.1.- (Racemases and Epimerases); EC 5.1.1.16 (serine racemase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE
[do] DOI:10.1111/jnc.14214


  6 / 1189 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28791861
[Au] Autor:Wang Z; Zhuang W; Cheng J; Sun W; Wu J; Chen Y; Ying H
[Ad] Endereço:State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University , No. 5 Xinmofan Road, Nanjing 210009, China.
[Ti] Título:In Vivo Multienzyme Complex Coconstruction of N-Acetylneuraminic Acid Lyase and N-Acetylglucosamine-2-epimerase for Biosynthesis of N-Acetylneuraminic Acid.
[So] Source:J Agric Food Chem;65(34):7467-7475, 2017 Aug 30.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Metabolic channeling enables efficient transfer of the intermediates by forming a multienzyme complex. To leverage the metabolic channeling for improved biosynthesis, we coexpressed N-acetylneuraminic acid lyase from C. glutamicum ATCC 13032 (CgNal) and N-acetylglucosamine-2-epimerase from Anabaena sp. CH1 (anAGE) in Escherichia coli and used the whole cell to synthesize N-acetylneuraminic acid (Neu5Ac) from N-acetylglucosamine (GlcNAc) and pyruvate. To get the multienzyme complex, polycistronic plasmid with high levels of CgNal and anAGE expression was constructed by tuning the orders of the genes. The Shine-Dalgarno (SD) sequence and aligned spacing (AS) distance were optimized. The E. coli Rosetta harboring the polycistronic plasmid pET-28a-SD -AS -CgNal-SD-AS-anAGE increased the production of Neu5Ac by 58.7% to 92.5 g/L in 36 h by whole-cell catalysis and by 21.9% up to 112.8 g/L in 24 h with the addition of Triton X-100.
[Mh] Termos MeSH primário: Anabaena/enzimologia
Proteínas de Bactérias/metabolismo
Corynebacterium glutamicum/enzimologia
Oxo-Ácido-Liases/metabolismo
Racemases e Epimerases/metabolismo
[Mh] Termos MeSH secundário: Acetilglucosamina/metabolismo
Proteínas de Bactérias/genética
Estabilidade Enzimática
Escherichia coli/genética
Escherichia coli/metabolismo
Expressão Gênica
Oxo-Ácido-Liases/química
Oxo-Ácido-Liases/genética
Racemases e Epimerases/química
Racemases e Epimerases/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); EC 4.1.3.- (Oxo-Acid-Lyases); EC 4.1.3.3 (N-acetylneuraminate lyase); EC 5.1.- (Racemases and Epimerases); V956696549 (Acetylglucosamine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170810
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.7b02708


  7 / 1189 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28696262
[Au] Autor:Nelson DL; Applegate GA; Beio ML; Graham DL; Berkowitz DB
[Ad] Endereço:From the Department of Chemistry, University of Nebraska, Lincoln, Nebraska 68588.
[Ti] Título:Human serine racemase structure/activity relationship studies provide mechanistic insight and point to position 84 as a hot spot for ß-elimination function.
[So] Source:J Biol Chem;292(34):13986-14002, 2017 Aug 25.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:There is currently great interest in human serine racemase, the enzyme responsible for producing the NMDA co-agonist d-serine. Reported correlation of d-serine levels with disorders including Alzheimer's disease, ALS, and ischemic brain damage (elevated d-serine) and schizophrenia (reduced d-serine) has further piqued this interest. Reported here is a structure/activity relationship study of position Ser , the putative -face base. In the most extreme case of functional reprogramming, the S84D mutant displays a dramatic reversal of ß-elimination substrate specificity in favor of l-serine over the normally preferred l-serine- -sulfate (∼1200-fold change in / ratios) and l (l-THA; ∼5000-fold change in / ratios) alternative substrates. On the other hand, the S84T (which performs l-Ser racemization activity), S84A (good but high for l-THA elimination), and S84N mutants (nearly WT efficiency for l-Ser elimination) displayed intermediate activity, all showing a preference for the anionic substrates, but generally attenuated compared with the native enzyme. Inhibition studies with l- -ß-hydroxyaspartate follow this trend, with both WT serine racemase and the S84N mutant being competitively inhibited, with = 31 ± 1.5 µm and 1.5 ± 0.1 mm, respectively, and the S84D being inert to inhibition. Computational modeling pointed to a key role for residue Arg-135 in binding and properly positioning the l-THA and l-serine- -sulfate substrates and the l- -ß-hydroxyaspartate inhibitor. Examination of available sequence data suggests that Arg-135 may have originated for l-THA-like ß-elimination function in earlier evolutionary variants, and examination of available structural data suggests that a Ser -H O-Lys hydrogen-bonding network in human serine racemase lowers the p of the Ser -face base.
[Mh] Termos MeSH primário: Arginina/química
Modelos Moleculares
Racemases e Epimerases/metabolismo
Serina/química
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Ligação Competitiva
Biocatálise
Biologia Computacional
Inibidores Enzimáticos/química
Inibidores Enzimáticos/farmacologia
Seres Humanos
Ligações de Hidrogênio
Cinética
Simulação de Acoplamento Molecular
Simulação de Dinâmica Molecular
Mutação
Domínios PDZ
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Filogenia
Conformação Proteica
Racemases e Epimerases/antagonistas & inibidores
Racemases e Epimerases/química
Racemases e Epimerases/genética
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Especificidade por Substrato
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Peptide Fragments); 0 (Recombinant Fusion Proteins); 0 (Recombinant Proteins); 452VLY9402 (Serine); 94ZLA3W45F (Arginine); EC 5.1.- (Racemases and Epimerases); EC 5.1.1.16 (serine racemase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170712
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.777904


  8 / 1189 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28683916
[Au] Autor:Bearne SL; St Maurice M
[Ad] Endereço:Dalhousie University, Halifax, NS, Canada. Electronic address: sbearne@dal.ca.
[Ti] Título:A Paradigm for CH Bond Cleavage: Structural and Functional Aspects of Transition State Stabilization by Mandelate Racemase.
[So] Source:Adv Protein Chem Struct Biol;109:113-160, 2017.
[Is] ISSN:1876-1623
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Mandelate racemase (MR) from Pseudomonas putida catalyzes the Mg -dependent, 1,1-proton transfer reaction that racemizes (R)- and (S)-mandelate. MR shares a partial reaction (i.e., the metal ion-assisted, Brønsted base-catalyzed proton abstraction of the α-proton of carboxylic acid substrates) and structural features ((ß/α) ß-barrel and N-terminal α + ß capping domains) with a vast group of homologous, yet functionally diverse, enzymes in the enolase superfamily. Mechanistic and structural studies have developed this enzyme into a paradigm for understanding how enzymes such as those of the enolase superfamily overcome kinetic and thermodynamic barriers to catalyze the abstraction of an α-proton from a carbon acid substrate with a relatively high pK value. Structural studies on MR bound to intermediate/transition state analogues have delineated those structural features that MR uses to stabilize transition states and enhance reaction rates of proton abstraction. Kinetic, site-directed mutagenesis, and structural studies have also revealed that the phenyl ring of the substrate migrates through the hydrophobic cavity within the active site during catalysis and that the Brønsted acid-base catalysts (Lys 166 and His 297) may be utilized as binding determinants for inhibitor recognition. In addition, structural studies on the adduct formed from the irreversible inhibition of MR by 3-hydroxypyruvate revealed that MR can form and deprotonate a Schiff-base with 3-hydroxypyruvate to yield an enol(ate)-aldehyde adduct, suggesting a possible evolutionary link between MR and the Schiff-base forming aldolases. As the archetype of the enolase superfamily, mechanistic and structural studies on MR will continue to enhance our understanding of enzyme catalysis and furnish insights into the evolution of enzyme function.
[Mh] Termos MeSH primário: Bactérias/enzimologia
Racemases e Epimerases/metabolismo
[Mh] Termos MeSH secundário: Bactérias/química
Bactérias/metabolismo
Domínio Catalítico
Cinética
Ácidos Mandélicos/química
Ácidos Mandélicos/metabolismo
Modelos Moleculares
Pseudomonas putida/química
Pseudomonas putida/enzimologia
Pseudomonas putida/metabolismo
Racemases e Epimerases/química
Especificidade por Substrato
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Mandelic Acids); EC 5.1.- (Racemases and Epimerases); EC 5.1.2.2 (mandelate racemase); NH496X0UJX (mandelic acid)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE


  9 / 1189 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28533113
[Au] Autor:Mori H; Wada R; Takahara S; Horino Y; Izumi H; Ishimoto T; Yoshida T; Mizuguchi M; Obita T; Gouda H; Hirono S; Toyooka N
[Ad] Endereço:Graduate School of Innovative Life Science, University of Toyama, Toyama 930-0194, Japan; Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
[Ti] Título:A novel serine racemase inhibitor suppresses neuronal over-activation in vivo.
[So] Source:Bioorg Med Chem;25(14):3736-3745, 2017 Jul 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Serine racemase (SRR) is an enzyme that produces d-serine from l-serine. d-Serine acts as an endogenous coagonist of NMDA-type glutamate receptors (NMDARs), which regulate many physiological functions. Over-activation of NMDARs induces excitotoxicity, which is observed in many neurodegenerative disorders and epilepsy states. In our previous works on the generation of SRR gene knockout (Srr-KO) mice and its protective effects against NMDA- and Aß peptide-induced neurodegeneration, we hypothesized that the regulation of NMDARs' over-activation by inhibition of SRR activity is one such therapeutic strategy to combat these disease states. In the previous study, we performed in silico screening to identify four compounds with inhibitory activities against recombinant SRR. Here, we synthesized 21 derivatives of candidate 1, one of four hit compounds, and performed screening by in vitro evaluations. The derivative 13J showed a significantly lower IC value in vitro, and suppressed neuronal over-activation in vivo.
[Mh] Termos MeSH primário: Acrilamidas/química
Inibidores Enzimáticos/química
Substâncias Protetoras/química
Racemases e Epimerases/antagonistas & inibidores
Tioureia/análogos & derivados
[Mh] Termos MeSH secundário: Acrilamidas/administração & dosagem
Acrilamidas/síntese química
Peptídeos beta-Amiloides/química
Peptídeos beta-Amiloides/metabolismo
Animais
Sítios de Ligação
Encéfalo/efeitos dos fármacos
Encéfalo/metabolismo
Inibidores Enzimáticos/metabolismo
Inibidores Enzimáticos/farmacologia
Seres Humanos
Ligações de Hidrogênio
Camundongos
Camundongos Knockout
Camundongos Transgênicos
Simulação de Acoplamento Molecular
Imagem Óptica
Substâncias Protetoras/síntese química
Substâncias Protetoras/farmacologia
Estrutura Terciária de Proteína
Racemases e Epimerases/genética
Racemases e Epimerases/metabolismo
Receptores de N-Metil-D-Aspartato/química
Receptores de N-Metil-D-Aspartato/metabolismo
Proteínas Recombinantes/biossíntese
Proteínas Recombinantes/química
Proteínas Recombinantes/isolamento & purificação
Tioureia/administração & dosagem
Tioureia/síntese química
Tioureia/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3-(3,5-dibromophenyl)-N-(N'-phenylacetylhydrazinocarbothioyl)acrylamide); 0 (Acrylamides); 0 (Amyloid beta-Peptides); 0 (Enzyme Inhibitors); 0 (Protective Agents); 0 (Receptors, N-Methyl-D-Aspartate); 0 (Recombinant Proteins); EC 5.1.- (Racemases and Epimerases); EC 5.1.1.16 (serine racemase); GYV9AM2QAG (Thiourea)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170524
[St] Status:MEDLINE


  10 / 1189 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28384107
[Au] Autor:Bachurska SY; Staykov DG; Bakardzhiev IV; Antonov PA; Belovezhdov VT
[Ad] Endereço:Department of General and Clinical Pathology and Forensic Medicine, Medical University of Plovdiv, 15A Vasil Aprilov Blvd., 4002 Plovdiv, Bulgaria.
[Ti] Título:Diagnostic Value of ERG in Prostate Needle Biopsies Containing Minute Cancer Foci.
[So] Source:Folia Med (Plovdiv);59(1):84-90, 2017 Mar 01.
[Is] ISSN:0204-8043
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Prostate carcinoma (PC) is the second most diagnosed cancer in men population worldwide. The small amount of the tissue in prostate needle biopsy is often sufficient for the correct interpretation. Novel antibodies, as ERG, could add to the diagnostic value of IHC study in analysing difficult core biopsies. AIM: The aim of the present study was to establish a diagnostic use of ERG in a work-up of prostate needle biopsies containing minute PC, individually and in combination with AMACR/34ßE12. MATERIALS AND METHODS: From total number of 1710 consecutive prostate needle biopsies based on HE stain 114 biopsies containing minute PC. Selected biopsies were incubated with anti-ERG, AMACR and 34ßE12 antibodies using immunohistochemical technique. RESULTS: Among 98 selected biopsies, 57 showed positive and 41 negative ERG staining. AMACR staining was positively expressed in 86 of the cases and completely absent in remaining 12. In 9 of the AMACR-negative cases the final diagnosis was establish by manifestation of ERG expression in the tumour foci. 95 of the biopsies demonstrated lack of 34ßE12 expression and only 3 cases showed weak patchy staining. Among these cases 2 were ERG-positive. CONCLUSION: ERG antibody could be especially helpful in the cases with controversial expression of AMACR and 34ßE12.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/metabolismo
Carcinoma/metabolismo
Queratinas/metabolismo
Neoplasias da Próstata/metabolismo
Racemases e Epimerases/metabolismo
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Biópsia por Agulha
Carcinoma/diagnóstico
Carcinoma/patologia
Seres Humanos
Imuno-Histoquímica
Calicreínas/sangue
Masculino
Meia-Idade
Antígeno Prostático Específico/sangue
Neoplasias da Próstata/diagnóstico
Neoplasias da Próstata/patologia
Regulador Transcricional ERG/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (CK-34 beta E12); 0 (ERG protein, human); 0 (Transcriptional Regulator ERG); 68238-35-7 (Keratins); EC 3.4.21.- (Kallikreins); EC 3.4.21.- (kallikrein-related peptidase 3, human); EC 3.4.21.77 (Prostate-Specific Antigen); EC 5.1.- (Racemases and Epimerases); EC 5.1.99.4 (alpha-methylacyl-CoA racemase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170622
[Lr] Data última revisão:
170622
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170407
[St] Status:MEDLINE



página 1 de 119 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde