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1.
Plant Physiol Biochem ; 157: 348-358, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33189055

RESUMO

An adequate amount of Sulfur (S) is essential for proper plant growth and defence against abiotic stresses including metals and metalloids. Arsenic (As) contamination is increasing in agricultural soils rapidly due to anthropogenic activities. Sulfur deficiency and arsenic stress could be more harmful than these individual stresses alone. To understand the impact of S-deficiency and arsenic (31 ppm Na3AsO4 of soil) on ecophysiology, growth, inorganic phosphate level, and proteomic profile of spinach, the present study was conducted. Interaction of arsenic with phosphate transporters, phytochelatins, and glutathione was also analyzed in silico. Comparative 2D MS/MS proteomics helped in the identification of important proteins which might be the key players under S-deficiency and As stress. Upregulation and downregulation of 36 and 21 proteins under As stress; 19 and 36 proteins under S-deficiency; 38 and 31 proteins under combined stress, respectively was observed. A total, 87 proteins subjected to identification via MS/MS ion search were found to be associated with important plant functions. PHO1 abundance was highly influenced by As stress; hence an in-silico homology modeling based molecular docking was performed which indicated high interaction between PHO1 and As/phosphate. Varied proximity of arsenic with phosphate transporters, phytochelatin, and glutathione revealed these components as a potential target of As toxicity/detoxification in Spinach, reflecting sulfur as an important criterion for arsenic tolerance.


Assuntos
Arsênio/toxicidade , Proteínas de Transporte de Fosfato/metabolismo , Fosfatos/metabolismo , Spinacia oleracea/metabolismo , Enxofre/metabolismo , Simulação de Acoplamento Molecular , Proteínas de Plantas/metabolismo , Proteômica , Spinacia oleracea/efeitos dos fármacos , Estresse Fisiológico , Espectrometria de Massas em Tandem , Regulação para Cima
2.
Curr Top Med Chem ; 20(12): 1059-1073, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903881

RESUMO

Microtubule-associated protein tau is involved in the tubulin binding leading to microtubule stabilization in neuronal cells which is essential for stabilization of neuron cytoskeleton. The regulation of tau activity is accommodated by several kinases which phosphorylate tau protein on specific sites. In pathological conditions, abnormal activity of tau kinases such as glycogen synthase kinase-3 ß (GSK3ß), cyclin-dependent kinase 5 (CDK5), c-Jun N-terminal kinases (JNKs), extracellular signal-regulated kinase 1 and 2 (ERK1/2) and microtubule affinity regulating kinase (MARK) lead to tau hyperphosphorylation. Hyperphosphorylation of tau protein leads to aggregation of tau into paired helical filaments like structures which are major constituents of neurofibrillary tangles, a hallmark of Alzheimer's disease. In this review, we discuss various tau protein kinases and their association with tau hyperphosphorylation. We also discuss various strategies and the advancements made in the area of Alzheimer's disease drug development by designing effective and specific inhibitors for such kinases using traditional in vitro/in vivo methods and state of the art in silico techniques.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases/metabolismo , Proteínas tau/antagonistas & inibidores , Doença de Alzheimer/metabolismo , Animais , Desenvolvimento de Medicamentos , Humanos , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteínas tau/metabolismo
3.
Int J Biol Macromol ; 96: 234-240, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27993657

RESUMO

C. trachomatis is a Gram-negative bacterium that causes trachoma and sexually transmitted disease (STD) Chlamydia in humans. Chlamydial genital infections are the most frequent among all communicable diseases. The D/UW-3/Cx strain of C. trachomatis contains 935 genes and three pseudogenes. Out of these genes, 887 genes code for proteins while six for rRNA, 37 tRNA, and three genes translate into other RNAs. The proteome of C. trachomatis made of 887 proteins contains 269 Hypothetical proteins (HPs) that are subjected to functional characterization. This study suggests some known methods of functional characterization of such HPs. All of these methods are explicitly used to assign functions to the HPs with the accuracy of more than 90%. After extensive analysis of all the HPs, we have successfully assigned functions to 89 HPs with high precision. In the newly assigned HPs, there are enzymes, transporters, binding proteins, proteins involved in biosynthesis and regulatory processes and proteins with miscellaneous functions. The study suggests that the functionally annotated HPs may play a vital role in the growth and pathogenesis of this organism. Therefore, they can be considered potential drug targets.


Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Chlamydia trachomatis/efeitos dos fármacos , Chlamydia trachomatis/genética , Genômica , Chlamydia trachomatis/metabolismo , Terapia de Alvo Molecular
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