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Cloning, Expression and Biochemical Characterization of the Recombinant α-amylase from Bacillus subtilis YX48 枯草芽孢杆菌YX48重组α-淀粉酶的克隆、表达及生化特性研究
IF 0.8 4区 生物学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2021-07-26 DOI: 10.2174/1570164618666210726161428
Y. Shan, Junjie Shang, Dongfang Zhang, Yinshan Cui, Yi Wang, Jie Zhu, Yongkai Ma, P. Song, K. Qin, X. Ji, Yunlin Wei, Lijun Wu
Amylase used in the market is mostly medium-temperature enzyme or high-temperature enzyme and has poor enzyme activity under low-temperature environment. Acid α-amylase can be used to develop digestion additives in the pharmaceutical and healthcare industries. The amino acid sequence and structural differences among α-amylases obtained from various organisms are high enough to confer interesting biochemical diversity to the enzymes. However, low- temperature (0-50℃) amylase, with an optimum temperature and heat sensitivity, has a greater potential value than medium (50-80℃) and high (80-110℃) temperature amylases.The gene amy48 from encoding extracellular α-amylase in Bacillus subtilis YX48 was successfully cloned into the pET30a (+) vector and expressed in Escherichia coli BL21 (DE3) for biochemical characterization. The molecular weight of α-amylase was 75 kDa. The activity of α-amylase was not affected by Ca2+, and Amy48 had the best activity at pH 5.0 and 37℃. AMY48 has high stability over a narrow pH and temperature range (5.0-8.0 and 30-45℃). Amylase activity was strongly inhibited by Zn2+, Mn2+, Cu2+, and Fe2+ ions, but Na+, K+, and Co2+ ions stimulate its activity slightly. The purified enzyme showed gradually reduced activity in the presence of detergents. However, it was remarkably stable against EDTA and urea.
市场上使用的淀粉酶多为中温酶或高温酶,在低温环境下酶活性较差。酸性α-淀粉酶可用于制药和保健行业开发消化添加剂。不同生物α-淀粉酶的氨基酸序列和结构差异足以赋予其有趣的生化多样性。而低温(0-50℃)淀粉酶具有最佳的温度和热敏性,比中温(50-80℃)和高温(80-110℃)淀粉酶具有更大的潜在价值。将枯草芽孢杆菌YX48胞外α-淀粉酶基因amy48成功克隆到pET30a(+)载体中,并在大肠杆菌BL21 (DE3)中表达,进行生化表征。α-淀粉酶分子量为75 kDa。α-淀粉酶活性不受Ca2+的影响,在pH 5.0和37℃条件下Amy48的活性最好。AMY48在较窄的pH值和温度范围(5.0-8.0和30-45℃)内具有较高的稳定性。Zn2+、Mn2+、Cu2+和Fe2+离子对淀粉酶活性有较强的抑制作用,而Na+、K+和Co2+离子对淀粉酶活性有轻微的刺激作用。纯化后的酶在洗涤剂的作用下活性逐渐降低。但对EDTA和尿素具有显著的稳定性。
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引用次数: 1
Evaluation of the Binding Affinity of a Gonadotropin-Releasing Hormone Analogue (GnRH-a) Buserelin through In Silico and In Vivo testing in Clarias magur 促性腺激素释放激素类似物(GnRH-a) Buserelin在Clarias magur体内和体内的结合亲和力评价
IF 0.8 4区 生物学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2021-04-26 DOI: 10.2174/1570164618666210426090916
Mukesh Kumar, M. Goswami, S. Nayak, P. Gireesh-Babu, A. Chaudhari
To evaluate the binding affinity and biological potency of gonadotropin releasing hormone analogue (GnRHa) Buserelin (‎C60H86N16O13) based on in silico and in vivo testing for induced breeding in Clarias magur. Many attempts have been made to induce C. magur but encouraging results have not yet been achieved. Hence, it is the need of the hour to find out more potent analogues or other bio-molecules for induced breeding in C. magur to facilitate sustainable aquaculture. To determine the binding affinity of C. magur GnRH receptor through in silico and its validation for induced breeding of C. magur. Buserelin (‎C60H86N16O13) was selected as the potential GnRHa after screening several peptides for their binding energy with the C. magur GnRH receptor. The induced breeding trial was set up at ICAR-CIFE Powarkheda Centre, M.P. India, and Buserelin was administered in different doses to the brooders along with the dopamine inhibitor domperidone. The standard treatment with the commercial salmon GnRH (sGnRH) analogue Ovaprim® (Syndel, USA) was used as the control. The 3-D structure of C. magur GnRH receptor was generated using MODELLER software. Molecular docking studies revealed the binding preference of the receptor as chicken (c) GnRH-II > Buserelin > sGnRH > catfish (cf) GnRH > human (m) GnRH. Though Buserelin showed better binding affinity compared to sGnRH, induced breeding experiments with magur showed similar performance of the ligands at the equivalent dose of 20 µg/kg B.W., but the spontaneous release of milt from the males was not obsereved in both the cases. Significantly better reproductive parameters were recorded with Buserelin at the dose of 30 µg/kg B.W. The study revealed that that the GnRHa Buserelin can be used as an effective inducing agent for breeding in C. magur.
目的评价促性腺激素释放激素类似物(GnRHa) Buserelin (C60H86N16O13)在Clarias magur诱导育种中的结合亲和力和生物学效力。人们曾多次尝试诱导C. magur,但尚未取得令人鼓舞的结果。因此,迫切需要找到更有效的类似物或其他生物分子来诱导马格尔红鳉的繁殖,以促进可持续的水产养殖。目的:通过硅片法测定麻豆GnRH受体的结合亲和力,并验证其在麻豆诱导育种中的应用。在筛选了与C. magur GnRH受体结合的多肽后,选择了Buserelin (C60H86N16O13)作为潜在的GnRHa。诱导繁殖试验是在印度mpp的ICAR-CIFE Powarkheda中心进行的,将不同剂量的Buserelin与多巴胺抑制剂多潘立酮一起施用于育仔鸡。以商业鲑鱼GnRH (sGnRH)类似物Ovaprim®(Syndel, USA)作为对照。利用modeler软件生成C. magur GnRH受体的三维结构。分子对接研究表明,该受体的结合偏好为鸡(c) GnRH- ii > Buserelin > sGnRH >鲶鱼(cf) GnRH >人(m) GnRH。虽然与sGnRH相比,Buserelin表现出更好的结合亲和力,但在同等剂量为20µg/kg B.W时,magur诱导繁殖实验显示其性能相似,但在这两种情况下,雄性均未观察到milt的自发释放。用30µg/kg体重剂量的Buserelin可获得较好的繁殖参数。研究表明,GnRHa Buserelin可作为一种有效的诱导剂,用于大鼠黄颡鱼的繁殖。
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引用次数: 1
Arsenite induced conformational changes and aggregation in human serum albumin (HSA) and its prevention by naringin 亚砷酸盐引起的人血清白蛋白(HSA)的构象改变和聚集及其柚皮苷的预防
IF 0.8 4区 生物学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2021-04-23 DOI: 10.2174/1570164618666210423131625
S. Fatima, Fareeha Arshad, Samreen Amani
Heavy metals and metalloids like arsenic, cadmium, mercury acts as denaturing agent for biomolecules. They interfere with protein’s physiological activity by forming a complex with the protein’s side chain or removing the essential metal ions from metalloproteins and replacing them. Protein aggregation is an extensive phenomenon in a cell and is linked with various pathological conditions. In this study, we aim to prove that proteins are highly susceptible to arsenite toxicity by arsenite-induced protein aggregation; and that naringin reduces the aggregation effect. Several biophysical techniques were employed to study the protein aggregation due to arsenite and its prevention by naringin. Through our experiments, the results showed that aggregation induced by arsenite was reduced in the presence of naringin at twice the concentration of arsenite.In conclusion, our study showed that naringin plays a protective role during HSA aggregation due to arsenite.
重金属和类金属,如砷、镉、汞,是生物分子的变性剂。它们通过与蛋白质侧链形成复合物或从金属蛋白中去除必需的金属离子并取代它们来干扰蛋白质的生理活动。蛋白质聚集是细胞内广泛存在的现象,与多种病理状况有关。在本研究中,我们旨在通过亚砷酸盐诱导的蛋白质聚集证明蛋白质对亚砷酸盐毒性高度敏感;柚皮苷降低了聚合效应。采用多种生物物理技术研究了亚砷酸盐引起的蛋白质聚集及其柚皮苷的预防作用。通过我们的实验,结果表明,在柚皮苷存在的情况下,在两倍浓度的亚砷酸盐存在下,亚砷酸盐诱导的聚集减少。综上所述,我们的研究表明,柚皮苷对亚砷酸盐引起的HSA聚集具有保护作用。
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引用次数: 0
Quantitative Proteomics Reveals SOS2-related Proteins in Arabidopsis under Salt Stress 盐胁迫下拟南芥sos2相关蛋白的定量蛋白质组学研究
IF 0.8 4区 生物学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2021-04-13 DOI: 10.2174/1570164618666210413105907
Xiang Yu, Xiaoyun Zhao, Yongqing Yang, Zhen Li
Soil salinity is a major issue that seriously affects plant growth and cultivated land utilization. Salt tolerance is one of the most fundamental biological processes that ensures plants survival. SOS2 is one of the most important components of the Salt Overly Sensitive (SOS) signaling pathway, which maintains plant ion homeostasis under salt stress. The SOS2-related signaling pathways remain incompletely exploited especially at the proteomics level.In this paper, proteins potentially interacting with and regulated by SOS2 in Arabidopsis were identified.The proteomes of Arabidopsis Wild Type (WT) and SOS2-deficient mutant (sos2-2) exposed to 100 mM NaCl for 6 h were compared, proteins were identified using data-independent acquisition-based quantitative proteomics strategy.A total of 7470 proteins were identified and quantified, 372 Differentially Expressed Proteins (DEP) were detected between WT and sos2-2 mutant under normal condition and 179 DEPs were identified under salt treatment. Functional analysis showed that the DEPs were mainly involved in protein binding and catalytic activity. Among the DEPs under salt stress, the protein expressions of AVP1, Photosystem II reaction center protein A, B, C, and stress-responsive protein (KIN2) were significantly up-regulated. LHCA1, LHCA2, LHCA4, ATPD and ATPE were significantly down-regulated. These proteins were involved in biological processes including: stress response, photosynthesis, transport and heat shock.These results revealed complexity of the functions of SOS2 in maintaining intracellular homeostasis, in addition to its function in sodium homeostasis. Plant salt resistance is not independent but closely related to metabolic processes including photosystem, ATP synthase, transport and other stress resistances.
土壤盐分是严重影响植物生长和耕地利用的重要问题。耐盐性是保证植物生存的最基本的生物过程之一。SOS2是盐过度敏感(Salt oversensitive, SOS)信号通路的重要组成部分,在盐胁迫下维持植物离子稳态。特别是在蛋白质组学水平上,sos2相关的信号通路仍未被完全利用。本文鉴定了拟南芥中可能与SOS2相互作用并受其调控的蛋白。将拟南芥野生型(WT)和sos2缺陷突变体(sos2-2)在100 mM NaCl处理6 h后的蛋白质组学进行比较,采用数据独立获取的定量蛋白质组学策略对蛋白质进行鉴定。共鉴定并定量了7470个蛋白,其中正常条件下WT与sos2-2突变体之间检测到372个差异表达蛋白(DEP),盐处理下检测到179个差异表达蛋白(DEP)。功能分析表明,DEPs主要参与蛋白质结合和催化活性。盐胁迫下的DEPs中,AVP1、光系统II反应中心蛋白A、B、C和应激响应蛋白(KIN2)的表达量显著上调。LHCA1、LHCA2、LHCA4、ATPD、ATPE显著下调。这些蛋白参与了胁迫反应、光合作用、运输和热休克等生物过程。这些结果揭示了SOS2在维持细胞内稳态方面的复杂功能,以及它在钠稳态方面的功能。植物的耐盐性不是独立的,而是与光系统、ATP合酶、转运等代谢过程密切相关。
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引用次数: 0
Critical Residues in HSP70 Nucleotide Binding Domain for Challenges in Drug Design HSP70核苷酸结合域的关键残基对药物设计的挑战
IF 0.8 4区 生物学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2021-04-13 DOI: 10.2174/1570164618666210413111223
Mustafa Ergul, F. Aktan, Yusuf Tutar
The association of a drug with its target protein correlates to its medicinal activity and the microenvironment plays a key role in this association. The key challenge is to identify mutations which unlikely to respond to designed drugs. Hsp70 is an anti-apoptotic factor and tumor cells overexpress Hsp70 to survive against anti-cancer agents. The impact of pathogenic mutations on Hsp70 is unknown. Elucidation of these alterations is essential to understand the molecular switch mechanism. Thus, critical spots on Hsp70 Nucleotide Binding Domain (NBD) are important since mutation-driven sensitivity may be useful in designing innovative inhibitors. ATP, AMP-PNP (non-hydrolyzable analog of ATP) along with commercially available compounds VER-155008 (ATP analog and competitive inhibitor) and MKT-077 (allosteric inhibitor of ADP bound form) were docked to Hsp70 NBD structure in silico to identify critical amino acids of inhibition mechanism. Site-directed mutagenesis of the determined critical residues along with ATP hydrolysis and luciferase refolding were performed. Wild-type and mutant Hsp70s were compared to determine the effect on protein functions in the presence or the absence of inhibitors.This study identified three mutants that have a loss of function for Hsp70, which may alter the drug inhibition activity as oncogenic cells have multiple mutations. Two commercial inhibitors employed here that mimic ATP and ADP states respectively are not affected by these mutational perturbations and displayed effective interference for Hsp70 functions. Designing inhibitors by considering these critical residues may improve drug design and increase drug efficiency.
药物与其靶蛋白的关联与其药物活性相关,微环境在这种关联中起着关键作用。关键的挑战是确定不太可能对设计的药物产生反应的突变。Hsp70是一种抗凋亡因子,肿瘤细胞通过过度表达Hsp70来对抗抗癌药物而存活。致病性突变对Hsp70的影响尚不清楚。阐明这些改变对于理解分子开关机制至关重要。因此,Hsp70核苷酸结合域(NBD)上的关键位点是重要的,因为突变驱动的敏感性可能有助于设计创新的抑制剂。将ATP、AMP-PNP (ATP的非水解类似物)以及市售化合物VER-155008 (ATP类似物和竞争性抑制剂)和MKT-077 (ADP结合形式的变构抑制剂)通过硅对接到Hsp70 NBD结构上,以确定抑制机制的关键氨基酸。对确定的关键残基进行定点诱变,并进行ATP水解和荧光素酶重折叠。比较野生型和突变型hsp70,以确定存在或不存在抑制剂时对蛋白质功能的影响。本研究确定了三种Hsp70功能缺失的突变体,这可能会改变药物抑制活性,因为致癌细胞具有多重突变。本文采用的两种商业抑制剂分别模拟ATP和ADP状态,它们不受这些突变扰动的影响,并对Hsp70功能表现出有效的干扰。通过考虑这些关键残留物来设计抑制剂可以改进药物设计并提高药物效率。
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引用次数: 0
Cytotoxic and Apoptotic Effect of Iris taochia Plant Extracts on Human Breast Cancer (MCF-7) Cells 桃红鸢尾提取物对人乳腺癌(MCF-7)细胞的细胞毒性和凋亡作用
IF 0.8 4区 生物学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2021-04-02 DOI: 10.2174/1570164618666210402152159
Burak Yazgan, O. Ozcelik, A. Ayar, Gülin Renda, Tuba Yıldırım
Iris taochia is an endemic plant in Turkey. Iris species has many biological effects such as antibacterial, antiinflammatory, antioxidant and anticancer properties. Apoptosis is a programmed cell death and this mechanism regulates the death of cancer cells. The aim of our work is to investigate how the Iris taochia extracts affect the apoptotic activity in the MCF7 cells. Cytotoxic dose and cell viability is determined by the MTT assay. Bad, Bax, Bcl-2, Bcl-W, Bid, Bim, Caspase 3, Caspase 8, CD40, CD40L, cIAP-2, CytoC, DR6, Fas, FasL, HSP27, HSP60, HSP70, HTRA, IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-5, IGFBP-6, IGF-1sR, Livin, p21, p27, p53, SMAC, Survivin, sTNF-R1, sTNF-R2, TNF-α, TNF-β, TRAILR-1, TRAILR-2, TRAILR-3, TRAILR-4 and XIAP proteins were measured by the membrane array kit.Iris taochia extracts exhibited significant cytotoxic effects on MCF7 cells and IC50 values ranging from 1.56 to 100 μg/mL. Our results indicate that MeOH extract of Iris taochia in MCF7 cells may be a regulator of cell death proteins, cell cycle and growth factors. DCM and EtOH extracts of Iris taochia have a limited effect on MCF7 cells. Especially, HSPs, which play a significant role in chemoresistance downregulating DCM and EtOH extracts of Iris taochia, whereas ligands and receptors of extrinsic apoptotic pathway are upregulated by these extracts.This is the first study to investigate the cytotoxic and apoptotic effect of Iris taochia extracts on MCF7 cells. Results also showed that Iris taochia reduced cell viability and induced apoptotic pathways as a potential regulator of cancer cell death.
鸢尾是土耳其的一种特有植物。鸢尾具有抗菌、抗炎、抗氧化、抗癌等多种生物学作用。细胞凋亡是一种程序性的细胞死亡,它调节着癌细胞的死亡。本研究旨在探讨鸢尾提取物对MCF7细胞凋亡活性的影响。MTT法测定细胞毒性剂量和细胞活力。采用膜阵列试剂盒检测Bad、Bax、Bcl-2、Bcl-W、Bid、Bim、Caspase 3、Caspase 8、CD40、CD40L、cIAP-2、CytoC、DR6、Fas、FasL、HSP27、HSP60、HSP70、HTRA、IGF-I、IGF-II、IGFBP-1、IGFBP-2、IGFBP-3、IGFBP-4、IGFBP-5、IGFBP-6、IGF-1sR、Livin、p21、p27、p53、SMAC、Survivin、sTNF-R1、sTNF-R2、TNF-α、TNF-β、TRAILR-1、TRAILR-2、TRAILR-3、TRAILR-4、XIAP蛋白。鸢尾花提取物对MCF7细胞具有显著的细胞毒作用,IC50值为1.56 ~ 100 μg/mL。结果提示桃红虹膜MeOH提取物对MCF7细胞可能具有调节细胞死亡蛋白、细胞周期和生长因子的作用。桃红鸢尾DCM和EtOH提取物对MCF7细胞的影响有限。特别是在化学耐药中起重要作用的HSPs下调桃红虹膜DCM和EtOH提取物,而这些提取物上调外源性凋亡途径的配体和受体。本研究首次探讨鸢尾提取物对MCF7细胞的细胞毒性和凋亡作用。结果还表明,桃红鸢尾可降低细胞活力,诱导细胞凋亡通路,作为癌细胞死亡的潜在调节剂。
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引用次数: 0
RNA-Seq Data Analysis Unveils Potential Conserved Micro-RNAs in Agave Deserti RNA-Seq数据分析揭示龙舌兰沙漠中潜在的保守微rna
IF 0.8 4区 生物学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2021-03-31 DOI: 10.2174/1570164617999200529122637
B. Jabbar, Batcho Agossa Anicet, M. Sarwar, B. Rashid, S. Hassan, T. Husnain
Exploring molecular mechanism of abiotic stress tolerance in plants is needed toovercome the deterioration of yield and quality of crop plants to meet the food security challengesof the growing population.MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate targetgene expression for modulating plant growth, development, and response to different stresses.Agave belonging to CAM plants’ has remarkable tolerance to extreme conditions of drought andheat; however, molecular mechanisms underlying this excellence are yet to explore.This study applies comparative genomics approach on available Transcriptome (RNA-Seq) data of Agave deserti to identify potential miRNAs, and miRNA targets.Transcriptome datasets consisting of 128,869 Agave contigs was processed to create localdatabase, for nucleotide homology analysis with 6,028 non-redundant plant miRNAs as querysequences. Protein coding sequences were removed, and potential pre-miRNA sequences were testedfor stability analysis based on a variety of factors, including but not limited to %G+C contentand minimum free energy (-ΔG), as a filter to remove pseudo pre-miRNAs.This study identified 30 unique miRNAs of Agave deserti harboring 14 different categoriesof precursors. Phylogenetic analysis revealed evolutionary relationship between newly identifiedpre-miRNAs with corresponding pre-miRNA homologues. Target genes of miRNAs werepredicted subsequently, and possible functions were defined by functional annotation analysis.The results of this study will pave the way for further research, exploring the molecularmechanisms in Agave deserti and the role of miRNAs in gene regulation under abiotic stresses.
探索植物抗非生物胁迫的分子机制是克服作物产量和品质下降的需要,是应对人口增长带来的粮食安全挑战的需要。MicroRNAs (miRNAs)是一种非编码小RNA分子,通过调控靶基因的表达来调节植物的生长、发育和对不同胁迫的反应。龙舌兰属CAM植物,对极端干旱和高温条件具有显著的耐受性;然而,这种卓越背后的分子机制还有待探索。本研究将比较基因组学方法应用于龙舌兰现有的转录组(RNA-Seq)数据,以鉴定潜在的miRNA和miRNA靶点。通过对128,869个龙舌兰序列的转录组数据进行处理,建立本地数据库,以6,028个非冗余植物mirna作为查询序列进行核苷酸同源性分析。去除蛋白质编码序列,并基于多种因素测试潜在的pre-miRNA序列进行稳定性分析,包括但不限于%G+C含量和最小自由能(-ΔG),作为去除伪pre-miRNA的过滤器。本研究鉴定了30个独特的龙舌兰mirna,包含14种不同的前体。系统发育分析揭示了新发现的pre-miRNA与相应的pre-miRNA同源物之间的进化关系。随后预测mirna的靶基因,并通过功能注释分析确定可能的功能。本研究结果将为进一步研究龙舌兰在非生物胁迫下的分子机制及mirna在基因调控中的作用奠定基础。
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引用次数: 0
Protein aggregation and self assembly in Health and Disease 健康与疾病中的蛋白质聚集与自组装
IF 0.8 4区 生物学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2021-02-23 DOI: 10.2174/1570164618666210223160742
A. Basak, S. Basak
Self-attachment of proteins leading to the formation of highly insoluble protein oligomers and aggregates has become an important focus of research owing to its diverse implications in pathophysiology and diseases. This has become a more frequent phenomenon in most neurological and neurodegenerative diseases as well as in dementia. In recent years such event of protein aggregation has linked to other disease conditions, disorders or adverse health conditions. Interestingly, aggregation of protein also plays role in development, growth or metabolism. Most often physiological proteins are initially bio-synthesised in native or nascent geometrical forms or conformations but later they undergo specific folding pattern and thereby acquire a stable configuration that is biologically relevant and active. It is highly important that these proteins remain in their biologically active configuration in order to exert their functional properties. Any alteration or change to this structural configuration can be detrimental to their specific functions and may cause pathological consequences leading to the onset of diseases or disorders. Several factors such as the action of chaperones, binding partners, physiological metal ions, pH level, temperature, ionic strength, interfacial exposure (solid-liquid, liquid-liquid, gas-liquid), mutation and post translational modification, chemical changes, interaction with small molecules such as lipids, hormones, etc. and solvent environment have been either identified or proposed as important factors in conferring the ultimate status of protein structure and configuration. Among many misfolding protein conformations, self-assembly or aggregation is the most significant. It leads to the formation of highly oligomeric self-aggregates that precipitate and interfere with many biochemical processes with serious pathological consequences. The most common implication of protein aggregation leading to the formation of deposits / plaques of various morphological types is the onset of neurological and neurodegenerative diseases that include Alzheimer’s, Parkinson’s, Huntington, ALS (Amyotrophic Lateral Sclerosis), CJD (Creutzfeldt Jakob Dementia), Prion diseases, Amyloidosis and other forms of dementia. However increasingly studies revealed that protein aggregation may also be associated with other diseases such as cancer, type 2 diabetes, renal, corneal and cardiovascular diseases. Protein aggregation diseases are now considered as part of “Proteinopathy” which refers to conditions where proteins become structurally abnormal or fail to fold into stable normal configurations. In this review, we reflect on various aspects of protein self-aggregation, potential underlying causes, mechanism, role of secondary structures, pathological consequences and possible intervention strategies as reported in published literatures.
蛋白质的自附着导致高度不溶性蛋白质寡聚物和聚集体的形成,由于其在病理生理学和疾病中的多种意义,已成为研究的重要焦点。这在大多数神经和神经退行性疾病以及痴呆症中已经成为一种更常见的现象。近年来,这种蛋白质聚集事件与其他疾病、失调或不良健康状况有关。有趣的是,蛋白质的聚集也在发育、生长或代谢中发挥作用。大多数情况下,生理蛋白最初以天然或新生的几何形式或构象进行生物合成,但后来它们经历了特定的折叠模式,从而获得了具有生物学相关性和活性的稳定构型。为了发挥其功能特性,这些蛋白质保持其生物活性结构是非常重要的。这种结构构型的任何改变或改变都可能损害它们的特定功能,并可能引起病理后果,导致疾病或失调的发作。伴侣、结合伙伴、生理金属离子、pH值、温度、离子强度、界面暴露(固-液、液-液、气-液)、突变和翻译后修饰、化学变化、与小分子(如脂类、激素等)的相互作用以及溶剂环境等因素已被确定或提出为决定蛋白质结构和构型最终状态的重要因素。在许多错误折叠的蛋白质构象中,自组装或聚集是最重要的。它导致形成高度低聚的自聚集体,沉淀并干扰许多生化过程,造成严重的病理后果。蛋白质聚集导致各种形态类型的沉积物/斑块形成的最常见含义是神经和神经退行性疾病的发病,包括阿尔茨海默氏症、帕金森氏症、亨廷顿氏症、肌萎缩性侧索硬化症(ALS)、克雅氏痴呆症(Creutzfeldt Jakob Dementia)、朊病毒病、淀粉样变性和其他形式的痴呆症。然而,越来越多的研究表明,蛋白质聚集也可能与其他疾病有关,如癌症、2型糖尿病、肾脏、角膜和心血管疾病。蛋白质聚集性疾病现在被认为是“蛋白质病”的一部分,“蛋白质病”指的是蛋白质在结构上异常或无法折叠成稳定的正常构型的情况。在这篇综述中,我们反思了蛋白质自聚集的各个方面,潜在的潜在原因,机制,二级结构的作用,病理后果和可能的干预策略,已发表的文献报道。
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引用次数: 3
Prediction of Protein Structural Classes: Features Extraction to Classification Algorithm 蛋白质结构类预测:特征提取到分类算法
IF 0.8 4区 生物学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2021-02-18 DOI: 10.2174/1570164618666210218141148
Xiaoqing Liu, Zhenyu Yang, Yaoxin Wang, Qi Dai
The fast growing of protein sequencing and protein structure data has promoted the development of the protein structural class prediction. Several prediction methods have been proposed to study protein folding rate, DNA binding sites, as well as reducing the search of conformational space and realizing the prediction of tertiary structure. This paper introduces the current approaches of protein structural class prediction and emphasize their steps from information extraction to classification algorithms.
蛋白质测序和蛋白质结构数据的快速增长促进了蛋白质结构类预测的发展。人们提出了几种预测方法来研究蛋白质折叠率、DNA结合位点,减少对构象空间的搜索,实现对三级结构的预测。本文介绍了目前蛋白质结构分类预测的方法,重点介绍了它们从信息提取到分类算法的步骤。
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引用次数: 1
Characterization of proteins from putative human DNA and RNA viruses. 推定的人类DNA和RNA病毒的蛋白质特性。
IF 0.8 4区 生物学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2021-02-12 DOI: 10.2174/1570164618666210212123850
C. Polanco, V. Uversky, G. Vargas-Alarcón, T. Buhse, A. Huberman, M. Márquez, Leire Andrés
In the vast variety of viruses known, there is a particular interest in those transmitted to humans and whose ability to disseminate represents a significant public health issue. The present study’s objective is to bioinformatically characterize the proteins of the two main divisions of viruses, RNA-viruses and DNA-viruses. In this work, a set of in-house computational programs was used to calculate the polarity/charge profiles and intrinsic disorder predisposition profiles of the proteins of several groups of viruses representing both types extracted from UniProt database. The efficiency of these computational programs was statistically verified. It was found that the polarity/charge profile of the proteins is, in most cases, an efficient discriminant that allows the re-creation of the taxonomy known for both viral groups. Additionally, the entire set of "reviewed" proteins in UniProt database was analyzed to find proteins with the polarity/charge profiles similar to those obtained for each viral group. This search revealed a substantial number of proteins with such polarity-charge profiles. Polarity/charge profile represents a physicochemical metric, which is easy to calculate, and which can be used to effectively identify viral groups from their protein sequences.
在已知的种类繁多的病毒中,人们对那些传播给人类的病毒特别感兴趣,它们的传播能力是一个重大的公共卫生问题。本研究的目的是对病毒的两种主要分裂,rna病毒和dna病毒的蛋白质进行生物信息学表征。在这项工作中,我们使用了一套内部计算程序来计算从UniProt数据库中提取的代表两种类型的几组病毒的蛋白质的极性/电荷谱和内在无序易感性谱。这些计算程序的效率得到了统计验证。研究发现,在大多数情况下,蛋白质的极性/电荷谱是一种有效的判别方法,可以重新创建已知的两种病毒组的分类。此外,对UniProt数据库中“审查”的全部蛋白质进行分析,以找到与每个病毒组获得的蛋白质具有相似极性/电荷谱的蛋白质。这项研究揭示了大量具有这种极性电荷谱的蛋白质。极性/电荷谱是一种易于计算的理化指标,可用于从蛋白质序列中有效识别病毒群。
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引用次数: 0
期刊
Current Proteomics
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