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1.
Plant Physiol Biochem ; 202: 107978, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37660607

RESUMO

Drought stress is one of the most serious threats to sustainable agriculture and is predicted to be further intensified in the coming decades. Therefore, understanding the mechanism of drought stress tolerance and the development of drought-resilient crops are the major goals at present. In recent years, noncoding microRNAs (miRNAs) have emerged as key regulators of gene expressions under drought stress conditions and are turning out to be the potential candidates that can be targeted to develop drought-resilient crops in the future. miRNAs are known to target and decrease the expression of various genes to govern the drought stress response in plants. In addition, emerging evidence also suggests a regulatory role of long non-coding RNAs (lncRNAs) in the regulation of miRNAs and the expression of their target genes by a process referred as miRNA sponging. In this review, we present the regulatory roles of miRNAs in the modulation of drought-responsive genes along with discussing their biosynthesis and action mechanisms. Additionally, the interactive roles of miRNAs with phytohormone signaling components have also been highlighted to present the global view of miRNA functioning under drought-stress conditions.


Assuntos
Secas , MicroRNAs , Produtos Agrícolas , Resistência à Seca , Agricultura , MicroRNAs/genética
2.
3.
Microb Pathog ; 178: 106052, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36906439

RESUMO

This article has been withdrawn at the request of the editor and publisher. The publisher regrets that an error occurred which led to the premature publication of this paper. This error bears no reflection on the article or its authors. The publisher apologizes to the authors and the readers for this unfortunate error. The full Elsevier Policy on Article Withdrawal can be found at (https://www.elsevier.com/about/policies/article-withdrawal).

4.
Front Plant Sci ; 13: 1034237, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36518497

RESUMO

The utilization of microorganisms with biocontrol activity against fungal and bacterial pathogens of plants is recognized as a promising, effective, and environment-friendly strategy to protect agricultural crops. We report the glyphosate-tolerant Pseudomonas resinovorans SZMC 25872 isolate as a novel strain with antagonistic potential towards the plant pathogenic bacterium Agrobacterium tumefaciens. In our studies, the growth of the P. resinovorans SZMC 25872 and A. tumefaciens SZMC 14557 isolates in the presence of 74 different carbon sources, and the effect of 11 carbon sources utilized by both strains on the biocontrol efficacy was examined. Seven variations of media with different carbon sources were selected for the assays to observe the biocontrol potential of the P. resinovorans strain. Also, 50% concentrations of the cell-free culture filtrates (CCF) obtained from medium amended with L-alanine or succinic acid as sole carbon source were found to be effective for the growth suppression of A. tumefaciens by 83.03 and 56.80%, respectively. The effect of 7 media on siderophore amount and the activity of extracellular trypsin- and chymotrypsin-like proteases, as well as esterases were also evaluated. Significant positive correlation was found between the siderophore amount and the percentage of inhibition, and the inhibitory effect of the CCFs obtained from medium amended with succinic acid was eliminated in the presence of an additional iron source, suggesting that siderophores produced by P. resinovorans play an important role in its antagonistic potential. The metabolic profile analysis of the P. resinovorans SZMC 25872 strain, performed by high performance liquid chromatography - high resolution mass spectrometry (HPLC-HRMS), has identified several previously not reported metabolites that might play role in the antagonistic effect against A. tumefaciens. Based on our findings we suggest that the possible inhibition modes of A. tumefaciens SZMC 14557 by P. resinovorans SZMC 25872 include siderophore-mediated suppression, extracellular enzyme activities and novel bioactive metabolites.

6.
Front Plant Sci ; 13: 952212, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35991457

RESUMO

Plant growth-promoting bacteria (PGPB) Azotobacter spp. is the most promising bacteria among all microorganisms. It is an aerobic, free-living, and N2-fixing bacterium that commonly lives in soil, water, and sediments. It can be used as a biofertilizer for plant growth and nutrient utilization efficiency. Maize is the highly consumed cereal food crop of the cosmopolitan population, and the sustainable maize productivity achieved by applying bacteria in combination with nitrogen phosphorus potassium (NPK) is promising. In the present study, a bacterial isolate (PR19). Azotobacter nigricans, obtained from the soil of an organic farm was evaluated for its plant growth promoting potential alone and in combination with an inorganic fertilizer (NPK) included. The bacterial cultue (PR19) was screened for its morphological, biochemical, and plant growth-promoting characteristics, sequenced by the 16S rDNA method, and submitted to NCBI for the confirmation of strain identification. Further, the inoculation effect of the bacterial culture (PR19) in combination with NPK on growth and yield parameters of maize under pot were analyzed. Based on phenotypic and molecular characteristics, PR19 was identified as Azotobacter nigricans it was submitted to NCBI genbank under the accession No. KP966496. The bacterial isolate possessed multiple plant growth-promoting (MPGP) traits such as the production of ammonia, siderophore, indole-3-acetic acid (IAA), and ACC Deaminase (ACCD). It showed phosphate solubilization activity and tolerance to 20% salt, wide range of pH 5-9, higher levels of trace elements and heavy metals, and resistance to multiple antibiotics. PR19 expressed significantly increased (p < 0.001) antioxidant enzyme activities (SOD, CAT, and GSH) under the abiotic stress of salinity and pH. In vitro condition, inoculation of maize with the PR19 showed a significant increase in seed germination and enhancement in elongation of root and shoot compared to untreated control. The combined application of the PR19 and NPK treatments showed similar significant results in all growth and yield parameters of maize variety SHIATS-M S2. This study is the first report on the beneficial effects of organic farm isolated PR19-NPK treatment combinations on sustainable maize productivity.

7.
Microorganisms ; 9(7)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34361927

RESUMO

Soil saltiness is a noteworthy issue as it results in loss of profitability and development of agrarian harvests and decline in soil health. Microorganisms associated with plants contribute to their growth promotion and salinity tolerance by employing a multitude of macromolecules and pathways. Plant growth promoting rhizobacteria (PGPR) have an immediate impact on improving profitability based on higher crop yield. Some PGPR produce 1-aminocyclopropane-1-carboxylic (ACC) deaminase (EC 4.1.99.4), which controls ethylene production by diverting ACC into α-ketobutyrate and ammonia. ACC deaminase enhances germination rate and growth parameters of root and shoot in different harvests with and without salt stress. Arbuscular mycorrhizal fungi (AMF) show a symbiotic relationship with plants, which helps in efficient uptake of mineral nutrients and water by the plants and also provide protection to the plants against pathogens and various abiotic stresses. The dual inoculation of PGPR and AMF enhances nutrient uptake and productivity of several crops compared to a single inoculation in both normal and stressed environments. Positively interacting PGPR + AMF combination is an efficient and cost-effective recipe for improving plant tolerance against salinity stress, which can be an extremely useful approach for sustainable agriculture.

8.
Genes Dis ; 8(5): 721-729, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34291144

RESUMO

In the era of antibiotic resistance, in silico prediction of bacterial resistome profiles, likely to be associated with inactivation of new potential antibiotics is of utmost importance. Despite this, to the best of our knowledge, no tool exists for such prediction. Therefore, under the rationale that drugs with similar structures have similar resistome profiles, we developed two models, a deterministic model and a stochastic model, to predict the bacterial resistome likely to neutralize uncharacterized but potential chemical structures. The current version of the tool involves the prediction of a resistome for Escherichia coli and Pseudomonas aeruginosa. The deterministic model on omitting two diverse but relatively less characterized drug classes, polyketides and polypeptides showed an accuracy of 87%, a sensitivity of 85%, and a precision of 89%, whereas the stochastic model predicted antibiotic classes of the test set compounds with an accuracy of 72%, a sensitivity of 75%, and a precision of 83%. The models have been implemented in both a standalone package and an online server, uCAREChemSuiteCLI and uCARE Chem Suite, respectively. In addition to resistome prediction, the online version of the suite enables the user to visualize the chemical structure, classify compounds in 19 predefined drug classes, perform pairwise alignment, and cluster with database compounds using a graphical user interface. AVAILABILITY: uCARE Chem Suite can be browsed at: https://sauravsaha.shinyapps.io/ucarechemsuite2/, and uCAREChemSuiteCLI can be installed from:1. CRAN (https://cran.r-project.org/package=uCAREChemSuiteCLI) and2. GitHub (https://github.com/sauravbsaha/uCAREChemSuiteCLI).

9.
Indian J Pathol Microbiol ; 64(Supplement): S63-S68, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34135140

RESUMO

In recent clinical practice the molecular diagnostics have been significantly empowered and upgraded by the use of Artificial Intelligence and its assisted technologies. The use of Machine leaning and Deep Learning Neural network architectures have brought in a new dimension in clinical oncological research and development. These algorithm based software system with enhanced digital image analysis have emerged into a new branch of digital pathology and contributed immensely towards precision medicine and personal diagnostics. In India, gastric cancer is one of the most common cancers in males as well as in females. Various molecular biomarkers are associated with gastric cancer development and progression of which HER2 protein, a transmembrane tyrosine kinase (TK) receptor of epidermal growth factor receptors (EGFRs) family is of prime importance. The EGF receptor expression in gastric cancer is linked with its prognostics and theragnostics. These expressions are assessed by immunohistochemistry (IHC) and molecular techniques such as Fluorescence in-situ hybridization (FISH), as per recommendations for HER2 targeted immunotherapy. These have motivated the software giants like Google Inc. to produce innovative state of art technologies mimicking human traits such as learning and problem solving skill sets. This field is still under development and is slowly evolving and capturing global importance in recent times. A literature search on PubMed was performed to access updated information for this manuscript.


Assuntos
Inteligência Artificial , Técnicas de Diagnóstico Molecular/métodos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Algoritmos , Biomarcadores Tumorais/genética , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Índia
10.
BMC Microbiol ; 21(1): 134, 2021 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-33932997

RESUMO

BACKGROUND: Fungal spores dispersed in the atmosphere may become cause of different pathological conditions and allergies for human beings. A number of studies have been performed to analyze the diversity of airborne fungi in different environments worldwide, and in particular in many urban areas in China. We investigated, for the first time, the diversity, concentration and distribution of airborne fungi in Tianjin city. We sampled 8 outdoor environments, using open plate method, during a whole winter season. Isolated fungi were identified by morphological and molecular analysis. Environmental factors which could influence the airborne fungi concentration (temperature, humidity, wind speed, and air pressure) were monitored and analyzed. The effect of different urban site functions (busy areas with high traffic flow and commercial activities vs. green areas) on airborne fungal diversity was also analyzed. RESULTS: A total of 560 fungal strains, belonging to 110 species and 49 genera of Ascomycota (80 %), Basidiomycota (18 %), and Mucoromycota (2 %) were isolated in this study. The dominant fungal genus was Alternaria (22 %), followed by Cladosporium (18.4 %), Naganishia (14.1 %), Fusarium (5.9 %), Phoma (4.11 %), and Didymella (4.8 %). A fungal concentration ranging from 0 to 3224.13 CFU m- 3 was recorded during the whole study. Permutational multivariate analysis showed that the month was the most influential factor for airborne fungal community structure, probably because it can be regarded as a proxy of environmental variables, followed by wind speed. The two analyzed environments (busy vs. green) had no detectable effect on the air fungal community, which could be related to the relatively small size of parks in Tianjin and/or to the study season. CONCLUSIONS: Our study shed light on the highly diverse community of airborne fungi characterizing the outdoor environments of Tianjin, and clarified the role that different environmental factors played in shaping the analyzed fungal community. The dominant presence of fungi with potential hazardous effect on human health, such as Alternaria, Cladosporium and Naganishia, deserves further attention. Our results may represent a valuable source of information for air quality monitoring, microbial pollution control, and airborne diseases prevention.


Assuntos
Microbiologia do Ar , Biodiversidade , Monitoramento Ambiental , Fungos/fisiologia , China , Cidades , Técnicas de Cultura , Estações do Ano , Esporos Fúngicos/fisiologia , Vento
11.
Environ Pollut ; 287: 117370, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34020262

RESUMO

Fruit wastes can be imperative to elevate economical biomass to biofuels production process at pilot scale. Because of the renewable features, huge availability, having low lignin content organic nature and low cost; these wastes can be of much interest for cellulase enzyme production. This review provides recent advances on the fungal cellulase production using fruit wastes as a potential substrate. Also, the availability of fruit wastes, generation and processing data and their potential applications for cellulase enzyme production have been discussed. Several aspects, including cellulase and its function, solid-state fermentation, process parameters, microbial source, and the application of enzyme in biofuels industries have also been discussed. Further, emphasis has been made on various bottlenecks and feasible approaches such as use of nanomaterials, co-culture, molecular techniques, genetic engineering, and cost economy analysis to develop a low-cost based comprehensive technology for viable production of cellulase and its application in biofuels production technology.


Assuntos
Celulase , Biocombustíveis , Biomassa , Celulase/metabolismo , Fermentação , Frutas/metabolismo , Lignina/metabolismo , Tecnologia
12.
J Fungi (Basel) ; 8(1)2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-35049961

RESUMO

Iron (Fe) is the fourth most abundant element on earth and represents an essential nutrient for life. As a fundamental mineral element for cell growth and development, iron is available for uptake as ferric ions, which are usually oxidized into complex oxyhydroxide polymers, insoluble under aerobic conditions. In these conditions, the bioavailability of iron is dramatically reduced. As a result, microorganisms face problems of iron acquisition, especially under low concentrations of this element. However, some microbes have evolved mechanisms for obtaining ferric irons from the extracellular medium or environment by forming small molecules often regarded as siderophores. Siderophores are high affinity iron-binding molecules produced by a repertoire of proteins found in the cytoplasm of cyanobacteria, bacteria, fungi, and plants. Common groups of siderophores include hydroxamates, catecholates, carboxylates, and hydroximates. The hydroxamate siderophores are commonly synthesized by fungi. L-ornithine is a biosynthetic precursor of siderophores, which is synthesized from multimodular large enzyme complexes through non-ribosomal peptide synthetases (NRPSs), while siderophore-Fe chelators cell wall mannoproteins (FIT1, FIT2, and FIT3) help the retention of siderophores. S. cerevisiae, for example, can express these proteins in two genetically separate systems (reductive and nonreductive) in the plasma membrane. These proteins can convert Fe (III) into Fe (II) by a ferrous-specific metalloreductase enzyme complex and flavin reductases (FREs). However, regulation of the siderophore through Fur Box protein on the DNA promoter region and its activation or repression depend primarily on the Fe availability in the external medium. Siderophores are essential due to their wide range of applications in biotechnology, medicine, bioremediation of heavy metal polluted environments, biocontrol of plant pathogens, and plant growth enhancement.

13.
Biomolecules ; 12(1)2021 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-35053191

RESUMO

Heavy metal (HM) toxicity has become a global concern in recent years and is imposing a severe threat to the environment and human health. In the case of plants, a higher concentration of HMs, above a threshold, adversely affects cellular metabolism because of the generation of reactive oxygen species (ROS) which target the key biological molecules. Moreover, some of the HMs such as mercury and arsenic, among others, can directly alter the protein/enzyme activities by targeting their -SH group to further impede the cellular metabolism. Particularly, inhibition of photosynthesis has been reported under HM toxicity because HMs trigger the degradation of chlorophyll molecules by enhancing the chlorophyllase activity and by replacing the central Mg ion in the porphyrin ring which affects overall plant growth and yield. Consequently, plants utilize various strategies to mitigate the negative impact of HM toxicity by limiting the uptake of these HMs and their sequestration into the vacuoles with the help of various molecules including proteins such as phytochelatins, metallothionein, compatible solutes, and secondary metabolites. In this comprehensive review, we provided insights towards a wider aspect of HM toxicity, ranging from their negative impact on plant growth to the mechanisms employed by the plants to alleviate the HM toxicity and presented the molecular mechanism of HMs toxicity and sequestration in plants.


Assuntos
Metais Pesados , Humanos , Metalotioneína , Metais Pesados/metabolismo , Metais Pesados/toxicidade , Desenvolvimento Vegetal , Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
14.
Biotechnol Lett ; 42(10): 1799-1827, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32648189

RESUMO

Agro-industrial residues and by-products are a crescent environmental problem since they are often discarded without proper treatment, and still have growing production. These residues are rich from a nutritional point of view and contain various industrial relevant compounds, such as phenolic compounds, fibers, vitamins, sugars and others. The crescent worrying about environmental issues has led researchers and industries to focus on "eco-friendly" solutions for everyday problems. In this sense, the use of enzymes for the valorization of agro-industrial residues is a safe and green alternative technology. Hence, this review aims to show the enzyme potential for the use and valorization of several agro-industrial residues, focusing on the most produced residues worldwide, such as fruits, grains and lignocellulosic residues, as well as a brief explanation of microbial enzymes, its production and optimization, altogether with tools to identify producing microorganisms.


Assuntos
Biomassa , Produtos Agrícolas , Enzimas , Resíduos Industriais , Eliminação de Resíduos , Biotecnologia , Frutas , Lignina
16.
J Cell Biochem ; 120(11): 18826-18844, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31286540

RESUMO

Hepatic copper levels differ among patients with Wilson disease (WD) and normal individuals depending on the dietary intake, copper bioavailability, and genetic factors. Copper chloride (CuCl2 ) caused dose-dependent reduction in cell viability of human teratocarcinoma (HepG2) cell line, measured using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Cells were exposed to different concentrations of CuCl2 in log doses and maximum cell viability reduction was recorded at 15 µg/mL. Toxic dose of CuCl2 is potent inducer of reactive oxygen species (ROS). Apoptosis as a pattern of cell death was confirmed through sub-G1 fraction and morphological changes such as mitochondrial depolarization, endoplasmic reticulum and lysosomal destabilization, phosphatidylserine translocation, and DNA damage. Our transcriptional and translational results strongly support apoptotic cell death. Using the available data present in dbSNP and bioinformatics tools, three nonsynonymous single nucleotide polymorphisms (nsSNPs) were identified as deleterious, reducing the stability of protein ATP7B. Structural analysis of native and mutant ATP7B proteins was investigated using molecular dynamics simulation (MDS) approach. Mutation in ATP7B gene might disturb the structural conformation and catalytic function of the ATP7B protein may be inducing WD. Hence, excess dietary intake of copper chloride must be avoided for safety of health to prevent from WD.


Assuntos
Carcinoma Hepatocelular , ATPases Transportadoras de Cobre , Degeneração Hepatolenticular , Neoplasias Hepáticas , Modelos Biológicos , Proteínas de Neoplasias , Apoptose , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Cobre/metabolismo , ATPases Transportadoras de Cobre/genética , ATPases Transportadoras de Cobre/metabolismo , Dano ao DNA , Células Hep G2 , Humanos , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Mutação , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Espécies Reativas de Oxigênio/metabolismo
17.
Sci Rep ; 9(1): 8185, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31160715

RESUMO

Tilletia indica (Ti) - a quarantined fungal pathogen of wheat and its pathogenesis is chiefly governed by pathogen effectors secreted inside the host plant. The de novo genome sequencing of several field isolates and stages available could be used for understanding the molecular pathogenesis. The presence of gaps and low coverage of assembled genomes poses a problem in accurate functional annotation of such functions. In the present study attempts were made to improve the Ti draft genome through reconciliation of globally available datasets of three highly virulent monoteliospore cultures of Ti field isolates. It has sequence depth of 107x and N50 scaffold size of 80,772 (more than 26 times as large as achieved in the draft assembly) with highest sequence contiguity, more accurate and nearly complete. Functional annotation revealed that Ti genome contains 9209 genes evolved with many expanded gene families and arranged mostly in a cluster. About 79% of Ti genes were orthologous to other basidiomycetes fungi, Around 7.93% proteins were having secretary signals and 6.66% were identified as highly virulent pathogenicity genes. Using improved Ti genome as a reference, the genomic variation was assessed with respect to repeats, SNPs/InDel, gene families and correct set of virulence associated genes during its life cycle. The comparative intra-species, inter-stage and inter-species genomic variation will have broader implications to understand the gene regulatory networks involved in growth, mating and virulence behaviour of Tilletia f. spp. and also for better appreciation of fungal biology and disease management.


Assuntos
Basidiomycota/genética , Redes Reguladoras de Genes/genética , Genoma Fúngico/genética , Doenças das Plantas/genética , Basidiomycota/patogenicidade , Hibridização Genômica Comparativa , Proteínas Fúngicas/genética , Mutação INDEL/genética , Anotação de Sequência Molecular , Doenças das Plantas/microbiologia , Triticum/genética , Triticum/crescimento & desenvolvimento , Triticum/microbiologia , Virulência/genética
18.
Pharmaceutics ; 11(4)2019 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-31013995

RESUMO

Tissue engineering technologies involving growth factors have produced one of the most advanced generations of diabetic wound healing solutions. Using this approach, a nanocomposite carrier was designed using Poly(d,l-lactide-co-glycolide) (PLGA)/Gelatin polymer solutions for the simultaneous release of recombinant human epidermal growth factor (rhEGF) and gentamicin sulfate at the wound site to hasten the process of diabetic wound healing and inactivation of bacterial growth. The physicochemical characterization of the fabricated scaffolds was carried out using scanning electron microscopy (SEM) and X-ay diffraction (XRD). The scaffolds were analyzed for thermal stability using thermogravimetric analysis and differential scanning calorimetry. The porosity, biodegradability, and swelling behavior of the scaffolds was also evaluated. Encapsulation efficiency, drug loading capacity, and in vitro drug release were also investigated. Further, the bacterial inhibition percentage and detailed in vivo biocompatibility for wound healing efficiency was performed on diabetic C57BL6 mice with dorsal wounds. The scaffolds exhibited excellent wound healing and continuous proliferation of cells for 12 days. These results support the applicability of such systems in rapid healing of diabetic wounds and ulcers.

19.
Infect Genet Evol ; 67: 101-111, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30396000

RESUMO

Ornithine decarboxylase (ODC) is an immediate precursor of polyamine biosynthesis in Serratia marcescens and a potential target for inhibition of its growth. We predicted the 3D structural conformation of ODC enzyme and validated it using MDS in our previous study. In this current study, the potential inhibitors of ODC were obtained by virtual screening of potential inhibitors from ZINC database and studied in depth for their different binding pose. Among the ten virtually screened inhibitors, Conessine exhibited the best binding with ODC and its inhibition property was studied further by MDS studies. The natural compound conessine is isolated from plant Holarrhena antidysenterica and it is studied against ODC of Serratia marcenses for its inhibitory potentials. This revealed unforeseen twisted position in root mean square fluctuation (RMSF) and ODC modelled conformation that influenced ligand binding. Both predicted model and ligand bound model were compared and found to be stable with Root Mean Square Deviation (RMSD) of approximately 7 nm and 0.25 nm to that of crystallographic structure over simulation time of 55 ns and 70 ns respectively. This work paves the way for future development of new drugs against nosocomial diseases caused by Serratia marcescens.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Simulação de Dinâmica Molecular , Serratia marcescens/efeitos dos fármacos , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/química , Sítios de Ligação , Domínio Catalítico , Avaliação Pré-Clínica de Medicamentos , Ligação de Hidrogênio , Ligantes , Conformação Molecular , Ligação Proteica , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Relação Quantitativa Estrutura-Atividade
20.
J Biomol Struct Dyn ; 37(13): 3513-3523, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30204049

RESUMO

Solute carrier family 24 member 5 (SLC24A5) is a gene that is associated with oculocutaneous albinism type 6 (OCA6) disorder and is involved in skin and hair pigmentation. It is involved in the maturation of melanosomes and melanin synthesis. SLC24A5 gene is located in the chromosomal position of 15q21.1. The present study involves the use of computational techniques in order to obtain a detailed picture of the most probable mutations that are associated with SLC24A5. From the observed result it was found that the mutation S145F is most deleterious and disease associated is predicted using several bioinformatics tools. The 3-D structures of native and mutant (S145F) were modeled in order to understand protein functionality using ab initio Robetta server. The modeled structure validation was done with ERRAT, Verify-3D, Procheck and RAMPAGE Ramachandran plot analysis. The most validated structure undergoes molecular dynamics simulations (MDS) study to understand the structural and functional behaviour of the native and mutant proteins. The MDS result showed the more flexibility in the native SLC24A5 structure. Due to mutation in the SLC24A5 protein structure it became more rigid and might disturb the conformational changes and glycosylation function of protein structure and might play role in inducing the OCA6. This study provides a significant insight into the underlying molecular mechanism involved in albinism associated with OCA6. It further helps scientists to develop a drug therapy against OCA 6 disease. Communicated by Ramaswamy H. Sarma.


Assuntos
Albinismo Oculocutâneo/genética , Antiporters/química , Antiporters/metabolismo , Simulação de Dinâmica Molecular , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Polimorfismo de Nucleotídeo Único , Antiporters/genética , Sítios de Ligação , Biologia Computacional , Humanos , Modelos Moleculares , Proteínas Mutantes/genética , Mutação , Ligação Proteica , Conformação Proteica
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