Amino Acid Sequence

氨基酸序列
  • 文章类型: Journal Article
    2019年冠状病毒病(COVID-19)是一种新型疾病,对全球人类生活和国家经济产生了毁灭性影响。这种疾病表现出相似的寄生特性,需要宿主的生物分子来生存和繁殖。基于其结构,位于COVID-19病毒表面的刺突糖蛋白严重急性呼吸综合征冠状病毒2(SARS-CoV-2刺突蛋白)是抗病毒药物开发的潜在热点。COVID-19病毒使协助攻击者的伴侣系统采取行动,因此有利于感染。为了研究SARS-CoV-2刺突蛋白与人类分子伴侣(HSPA8和sHSP27)之间的相互作用,进行了一系列步骤,包括序列获得和分析,然后是多个序列比对,同源建模,和蛋白质-蛋白质对接,我们使用Cluspro进行预测SARS-CoV-2刺突蛋白与感兴趣的人类分子伴侣之间的相互作用。我们的发现描述了SARS-CoV-2刺突蛋白由三条不同的链组成,链条A,B,C,它们相互作用形成氢键,疏水相互作用,以及与人HSPA8和HSP27的静电相互作用,其中-828.3和-827.9kcal/mol作为人HSPA8和-1166.7和-1165.9kcal/mol的结合能。
    Coronavirus disease 2019 (COVID-19) is a novel disease that had devastating effects on human lives and the country\'s economies worldwide. This disease shows similar parasitic traits, requiring the host\'s biomolecules for its survival and propagation. Spike glycoproteins severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 spike protein) located on the surface of the COVID-19 virus serve as a potential hotspot for antiviral drug development based on their structure. COVID-19 virus calls into action the chaperonin system that assists the attacker, hence favoring infection. To investigate the interaction that occurs between SARS-CoV-2 spike protein and human molecular chaperons (HSPA8 and sHSP27), a series of steps were carried out which included sequence attainment and analysis, followed by multiple sequence alignment, homology modeling, and protein-protein docking which we performed using Cluspro to predict the interactions between SARS-CoV-2 spike protein and human molecular chaperones of interest. Our findings depicted that SARS-CoV-2 spike protein consists of three distinct chains, chains A, B, and C, which interact forming hydrogen bonds, hydrophobic interactions, and electrostatic interactions with both human HSPA8 and HSP27 with -828.3 and -827.9 kcal/mol as binding energies for human HSPA8 and -1166.7 and -1165.9 kcal/mol for HSP27.
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  • 文章类型: Journal Article
    奥古斯丁是一种新发现的包含四种抗原的血型系统,其中之一是原始“系列”中的高频抗原Ata。四个抗原位于多遍膜糖蛋白平衡核苷转运蛋白1(ENT1)上,和平衡核苷转运蛋白由SLC29A1编码。2016年,国际输血学会(ISBT)将奥古斯丁视为血型系统,并将其编号为036。糖蛋白ENT1将核苷酸转运到细胞中参与DNA和RNA的合成,这是化疗苷进入肿瘤细胞的重要环节。奥古斯丁抗体与输血和妊娠临床相关。
    Augustine is a newly identified blood group system comprising four antigens, one of which is the high-frequency antigen Ata in the original \"series\". Four antigens are located on a multipass membrane glycoprotein equilibrative nucleoside transporter 1 (ENT1), and equilibrative nucleoside transporter is encoded by SLC29A1. In 2016, the International Society of Blood Transfusion (ISBT) recognised Augustine as a blood group system and numbered it as 036. The glycoprotein ENT1 transports nucleotides into cells to participate in the synthesis of DNA and RNA, and this is an important link for chemotherapeutic glycosides to enter tumour cells. Augustine antibodies are clinically relevant in blood transfusion and pregnancy.
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  • 文章类型: Journal Article
    自1980年代以来,来自无性系皮肤分泌物的抗菌肽(AMP)的研究揭示了显着的结构多样性和广泛的活性。本研究通过审查已授予的专利来探索这些肽在药物开发中的潜力,与专利肽相关的氨基酸修饰,以及最近影响AMP名称的两栖动物分类更新。共发现了与不同无素肽相关的188项授权专利,亚洲和北美是主要地区,贡献了65.4%和15.4%,分别。相反,尽管新热带地区是世界上两栖动物最多样化的地区,它只拥有3.7%的已确认专利。在这188个专利中的118个中要求保护肽的抗微生物活性。此外,对于这些肽中的160种,天然序列注册了66项专利,69对于天然和衍生序列,和20专门用于序列衍生物。值得注意的是,常见的修饰包括氨基酸侧链的改变和肽N-和C-末端的修饰。这篇综述强调了无糖衍生的AMPs的生物医学潜力,强调需要弥合AMP描述与实际药物开发之间的差距,同时强调生物多样性保护以促进生物医学发现的紧迫性。
    Since the 1980s, studies of antimicrobial peptides (AMPs) derived from anuran skin secretions have unveiled remarkable structural diversity and a wide range of activities. This study explores the potential of these peptides for drug development by examining granted patents, amino acid modifications related to patented peptides, and recent amphibians\' taxonomic updates influencing AMP names. A total of 188 granted patents related to different anuran peptides were found, with Asia and North America being the predominant regions, contributing 65.4% and 15.4%, respectively. Conversely, although the Neotropical region is the world\'s most diversified region for amphibians, it holds only 3.7% of the identified patents. The antimicrobial activities of the peptides are claimed in 118 of these 188 patents. Additionally, for 160 of these peptides, 66 patents were registered for the natural sequence, 69 for both natural and derivative sequences, and 20 exclusively for sequence derivatives. Notably, common modifications include alterations in the side chains of amino acids and modifications to the peptides\' N- and C-termini. This review underscores the biomedical potential of anuran-derived AMPs, emphasizing the need to bridge the gap between AMP description and practical drug development while highlighting the urgency of biodiversity conservation to facilitate biomedical discoveries.
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  • 文章类型: Journal Article
    食品衍生的寡肽(FOP)表现出各种生物活性。然而,对它们在胃肠道中的序列变化以及变化对生物活性的影响知之甚少。FOP\'序列特征,对生物活性的变化和影响进行了总结。在模拟胃肠道消化过程中,随着末端疏水性和碱性氨基酸暴露的增加,FOP的序列长度减少。模拟肠道吸收后生物活性的降低与Leu的降低相关,Ile,Arg,Tyr,Gln和Pro。容易通过肠上皮的FOP序列对应于运输模式,和FOP,其序列在运输后保持不变是最具生物活性的。这些主要包括二肽到四肽,由许多疏水性和碱性氨基酸组成,主要位于肽链的末端,尤其是在C端。本综述旨在为FOP在营养补充剂和功能食品中的应用提供基础。
    Food-derived oligopeptides (FOPs) exhibit various bioactivities. However, little was known about their sequence changes in the gastrointestinal tract and the effect of changes on bioactivities. FOPs\' sequence features, changes and effects on bioactivities have been summarised. The sequence length of FOPs decreases with increased exposure of hydrophobic and basic amino acids at the terminal during simulated gastrointestinal digestion. A decrease in bioactivities after simulated intestinal absorption has correlated with a decrease of Leu, Ile, Arg, Tyr, Gln and Pro. The sequence of FOPs that pass readily through the intestinal epithelium corresponds to transport modes, and FOPs whose sequences remain unchanged after transport are the most bioactive. These include mainly dipeptides to tetrapeptides, consisting of numerous hydrophobic and basic amino acids, found mostly at the end of the peptide chain, especially at the C-terminal. This review aims to provide a foundation for applications of FOPs in nutritional supplements and functional foods.
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  • 文章类型: Journal Article
    神经肽参与昆虫几乎所有的生理活动。它们的分类基于生理功能和一级氨基酸序列。焦激肽(PK)/信息素生物合成激活神经肽(PBAN)是昆虫中最大的神经肽家族之一,具有FXPRLamide的保守C末端结构域。肽家族分为两组,PK1/滞育激素(DH)具有WFGPRLaC末端末端,PK2/PBAN具有FXPRLamideC末端。尖端技术发展以来,越来越多的肽主要通过基因组测序,转录组学,和蛋白质组学,以及使用基因编辑工具发现它们的功能。在这次审查中,我们讨论了新发现的函数,并分析了编码这些肽的基因在不同昆虫顺序中的分布。此外,还描述了通过PCR或免疫细胞化学确认的肽的位置。根据大多数昆虫目受体的序列构建了系统发育树。这篇综述提供了对这种保守肽家族在昆虫中的重要性的理解。
    Neuropeptides are involved in almost all physiological activities of insects. Their classification is based on physiological function and the primary amino acid sequence. The pyrokinin (PK)/pheromone biosynthesis activating neuropeptides (PBAN) are one of the largest neuropeptide families in insects, with a conserved C-terminal domain of FXPRLamide. The peptide family is divided into two groups, PK1/diapause hormone (DH) with a WFGPRLa C-terminal ending and PK2/PBAN with FXPRLamide C-terminal ending. Since the development of cutting-edge technology, an increasing number of peptides have been sequenced primarily through genomic, transcriptomics, and proteomics, and their functions discovered using gene editing tools. In this review, we discussed newly discovered functions, and analyzed the distribution of genes encoding these peptides throughout different insect orders. In addition, the location of the peptides that were confirmed by PCR or immunocytochemistry is also described. A phylogenetic tree was constructed according to the sequences of the receptors of most insect orders. This review offers an understanding of the significance of this conserved peptide family in insects.
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  • 文章类型: Journal Article
    对2016年至2020年之间批准的93种治疗性蛋白质的生物许可申请(BLA)进行了分析,以使用质谱(MS)作为先前研究的后续研究,该研究评估了2000年至2015年在BLA中使用MS的情况。这些BLAs中有30%是生物仿制药,而在2016年之前,只有一种生物类似药BLA获得批准。该分析评估了各种MS技术和仪器的使用。根据MS使用随时间的关系进一步解释结果,在药物类型之间,在新药和生物仿制药之间。MS数据包括在所检查的93个BLAs中。按等级排序,MS评估最多的前8个质量属性是氨基酸序列,分子量,氧化,二硫键,脱酰胺,糖基化,N端序列变体,和C端序列变体。这些属性与以前从2000年至2015年批准的BLAs中看到的最高属性相同,并且使用MS分析它们通常在新的时间框架内继续增加。在21年的延长时间范围内,每个BLAMS分析的平均属性数也继续增加。高分辨率,精确的质量仪器,如Orbitrap和飞行时间(TOF)的使用随着时间的推移而增加,所有评估的属性,而基质辅助激光解吸/电离(MALDI)-TOF/(TOF)使用率下降。从最高等级到最低等级,前11个属性是抗体药物缀合物(ADC)表征(即,载药量分布/药物抗体比(DAR),ADC和链接站点,和合成接头),异构化,折叠/高阶结构(HOS),截断,宿主细胞蛋白(HCP),序列变异(氨基酸取代),琥珀酰亚胺,糖化,聚乙二醇化,电荷变体,和氧化。
    Biologic license applications (BLAs) for 93 therapeutic proteins approved between 2016 and 2020 were analyzed for use of mass spectrometry (MS) as a follow up to a previous study that assessed MS use in BLAs from 2000 to 2015. Thirty percent of these BLAs were biosimilars, while only one biosimilar BLA was approved prior to 2016. This analysis evaluated the use of a variety of MS techniques and instrumentation. Results were further interpreted based on the relationship of MS use over time, between drug types, and between new drugs and biosimilars. MS data were included in 93 BLAs examined. The top eight quality attributes most assessed by MS in rank order were amino acid sequence, molecular mass, oxidation, disulfide bonds, deamidation, glycosylation, N-terminal sequence variants, and C-terminal sequence variants. These attributes were the same top attributes seen previously from BLAs approved between 2000 and 2015, and the use of MS to analyze them generally continued to increase across the new time frame. The average number of attributes analyzed by MS per BLA also continued to increase over the extended time frame of 21 years. High-resolution, accurate mass instrumentation such as the Orbitrap and time-of-flight (TOF) usage increased over time for all assessed attributes, while matrix-assisted laser desorption/ionization (MALDI)-TOF/(TOF) usage decreased. From highest to lowest rank, the top 11 attributes were antibody drug conjugate (ADC) characterization (i.e., drug load distribution/drug to antibody ratio (DAR), ADC and linkage site, and synthetic linker), isomerization, folding/higher-order structure (HOS), truncation, host cell proteins (HCPs), sequence variants (amino acid substitutions), succinimidation, glycation, PEGylation, charge variants, and oxidation.
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  • 文章类型: Journal Article
    TA,包括盐酸和东莨菪碱,用于治疗神经肌肉疾病,从神经毒剂中毒到帕金森病。托品酮还原酶I(TR-I;EC1.1.1.206)在TA的生物合成中催化托品酮转化为托品,引导代谢流向盐酸和东pol碱。托品酮还原酶II(TR-II;EC1.1.1.236)负责将托品酮转化为假托品,将代谢通量转向calysteginA3。通过TA途径的两个分支的代谢物流的调节似乎受到两种酶的酶活性及其对前体托品酮的可及性的影响。对利用代谢工程来有效生产TA的重大兴趣强调了TR作为控制代谢流方向和产物产率的关键酶的重要性。这篇综述讨论了TRs来源的最新进展,属性,蛋白质结构和生物催化机理,并对其在TAs代谢和合成中的关键作用进行了详细的概述。此外,我们对这两个TRs的进化起源进行了详细的调查。对TR的潜在挑战和应用进行了前瞻性分析。
    TAs, including hyoscyamine and scopolamine, were used to treat neuromuscular disorders ranging from nerve agent poisoning to Parkinson\'s disease. Tropinone reductase I (TR-I; EC 1.1.1.206) catalyzed the conversion of tropinone into tropine in the biosynthesis of TAs, directing the metabolic flow towards hyoscyamine and scopolamine. Tropinone reductase II (TR-II; EC 1.1.1.236) was responsible for the conversion of tropinone into pseudotropine, diverting the metabolic flux towards calystegine A3. The regulation of metabolite flow through both branches of the TAs pathway seemed to be influenced by the enzymatic activity of both enzymes and their accessibility to the precursor tropinone. The significant interest in the utilization of metabolic engineering for the efficient production of TAs has highlighted the importance of TRs as crucial enzymes that govern both the direction of metabolic flow and the yield of products. This review discussed recent advances for the TRs sources, properties, protein structure and biocatalytic mechanisms, and a detailed overview of its crucial role in the metabolism and synthesis of TAs was summarized. Furthermore, we conducted a detailed investigation into the evolutionary origins of these two TRs. A prospective analysis of potential challenges and applications of TRs was presented.
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  • 文章类型: Journal Article
    肽核酸(PNA)是一种对天然DNA或RNA具有高特异性和结合亲和力的核酸模拟物,以及对酶降解的抗性。PNA序列可以被设计为选择性地沉默基因表达,这使得PNA成为抗菌应用的有前途的工具。然而,PNA的膜通透性差仍然是其在细胞中应用的主要限制因素。为了克服这个障碍,已经开发了具有不同分子的PNA缀合物。这篇小型综述侧重于PNA与细胞穿透肽的共价连接缀合物,氨基糖,氨基糖苷类抗生素,和测试过的非肽分子,主要作为PNA携带者,在抗菌和抗病毒应用。还讨论了缀合的化学性质和应用的接头。
    Peptide nucleic acid (PNA) is a nucleic acid mimic with high specificity and binding affinity to natural DNA or RNA, as well as resistance to enzymatic degradation. PNA sequences can be designed to selectively silence gene expression, which makes PNA a promising tool for antimicrobial applications. However, the poor membrane permeability of PNA remains the main limiting factor for its applications in cells. To overcome this obstacle, PNA conjugates with different molecules have been developed. This mini-review focuses on covalently linked conjugates of PNA with cell-penetrating peptides, aminosugars, aminoglycoside antibiotics, and non-peptidic molecules that were tested, primarily as PNA carriers, in antibacterial and antiviral applications. The chemistries of the conjugation and the applied linkers are also discussed.
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  • 文章类型: Journal Article
    来自蚕蚕的丝素蛋白(SF)纤维以丝绸II形式已被用作优异的纺织纤维超过5000年。最近,它已被开发用于一系列生物医学应用。这些用途的进一步扩展建立在SF纤维优异的机械强度,这源于它的结构。强度和SF结构之间的这种关系已经研究了50多年,但它仍然没有得到很好的理解。在这次审查中,我们报告了使用固态NMR研究稳定同位素标记的SF纤维和稳定同位素标记的肽,包括(Ala-Gly)15和(Ala-Gly-Ser-Gly-Ala-Gly)5作为模型的结晶部分。我们表明,结晶部分是层状结构,每第八个氨基酸使用β转角进行重复折叠,侧链采用反极性排列,而不是马什描述的更著名的极性结构,科里和鲍林(也就是说,每层中的Ala甲基在交替的链中指向相反的方向)。氨基酸Ser,Tyr和Val在B.moriSF中仅次于Gly和Ala,并发生在结晶和半结晶区域,可能定义了结晶区域的边缘。因此,我们现在对丝绸II的主要特征有了了解,但还有很长的路要走。
    Silk fibroin (SF) fiber from the silkworm Bombyx mori in the Silk II form has been used as an excellent textile fiber for over 5000 years. Recently it has been developed for a range of biomedical applications. Further expansion of these uses builds on the excellent mechanical strength of SF fiber, which derives from its structure. This relationship between strength and SF structure has been studied for over 50 years, but it is still not well understood. In this review, we report the use of solid-state NMR to study stable-isotope labeled SF fiber and stable-isotope labeled peptides including (Ala-Gly)15 and (Ala-Gly-Ser-Gly-Ala-Gly)5 as models of the crystalline fraction. We show that the crystalline fraction is a lamellar structure with a repetitive folding using β-turns every eighth amino acid, and that the sidechains adopt an antipolar arrangement rather than the more well-known polar structure described by Marsh, Corey and Pauling (that is, the Ala methyls in each layer point in opposite directions in alternate strands). The amino acids Ser, Tyr and Val are the next most common in B. mori SF after Gly and Ala, and occur in the crystalline and semi-crystalline regions, probably defining the edges of the crystalline region. Thus, we now have an understanding of the main features of Silk II but there is still a long way to go.
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  • 文章类型: Journal Article
    多肽测序对化学等领域的基础和应用研究具有重要意义。生物,医学和药物科学。随着质谱和测序算法的快速发展,使用串联质谱(MS/MS)的从头肽测序已成为确定新型和未知肽氨基酸序列的主要方法。先进的算法可以在短时间内从MS/MS光谱中准确获得氨基酸序列信息。在这次审查中,介绍并比较了从穷举搜索到最先进的机器学习和用于高通量和自动从头测序的神经网络的算法。强调了数据集对算法性能的影响。本文还讨论了从头肽测序的当前局限性和有希望的方向。
    Peptide sequencing is of great significance to fundamental and applied research in the fields such as chemical, biological, medicinal and pharmaceutical sciences. With the rapid development of mass spectrometry and sequencing algorithms, de-novo peptide sequencing using tandem mass spectrometry (MS/MS) has become the main method for determining amino acid sequences of novel and unknown peptides. Advanced algorithms allow the amino acid sequence information to be accurately obtained from MS/MS spectra in short time. In this review, algorithms from exhaustive search to the state-of-art machine learning and neural network for high-throughput and automated de-novo sequencing are introduced and compared. Impacts of datasets on algorithm performance are highlighted. The current limitations and promising direction of de-novo peptide sequencing are also discussed in this review.
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