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Structure and Function of Eukaryotic DNA-Binding Proteins in DNA Repair 真核生物DNA结合蛋白在DNA修复中的结构与功能
Pub Date : 2011-12-31 DOI: 10.15866/IREBIC.V2I6.1543
S. J. Kind, M. Sanderson
This article reviews the current status of how structural studies are impacting on our understanding of the mechanism of Eukaryotic repair from a function standpoint. A wide array of different repair mechanisms are covered, namely DNA base excision repair (BER), nucleotide excision repair (NER) and mismatch repair (MMR)
本文综述了结构研究如何从功能角度影响我们对真核细胞修复机制的理解的现状。它涵盖了一系列不同的修复机制,即DNA碱基切除修复(BER)、核苷酸切除修复(NER)和错配修复(MMR)。
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引用次数: 0
Study of Biomolecular Recognition Using Time-Resolved Optical Spectroscopy 生物分子识别的时间分辨光谱学研究
Pub Date : 2011-12-31 DOI: 10.15866/IREBIC.V2I6.1545
Tanumoy Mondol, Soma Banerjee, Subrata Batabyal, S. Pal
Molecular recognition process refers to the weak non-covalent interaction, which takes place selectively and specifically between small ligand molecules with biological macromolecules. Understanding of such recognition in biological and biomimetic milieu is the central attraction for drug designing, which is crucial for the improvement of human healthcare. A thorough knowledge of the structural, dynamical and energetic parameters that dictate such molecular interactions can find immense use in the modulations of the ligand-macromolecule recognition process. In this article, we present our continuous effort to investigate the fundamental physical processes involved in the biomolecular recognition, e.g. efficiency (binding affinity and rigidity of the complex) and role of solvent molecules in the molecular recognition using steady state and predominantly, ultrafast time-resolved fluorescence spectroscopy. In this perspective, we have thoroughly investigated the molecular recognition of small ligand/drug molecules (Rifampicin; Rf, 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; DCM, and Nile Blue; NB) by a human transporter protein, Human Serum Albumin (HSA), and also established the nonspecific type of interaction between a ligand molecule (Rf) and a biomimetic system (Sodium Dodecyl Sulfate (SDS) micelle). Simultaneous recognition of an intercalator (Ethidium Bromide, EtBr) and a DNA minor groove binder (Hoeschst 33258, H258) to a dodecamer DNA of specific sequence has also been monitored. Besides, we report an investigation on the recognition of ethidium (Et) cation, a potential mutagen, by synthetic DNA and various cell nuclei in presence of a stimulant drug, caffeine, employing the mentioned spectroscopic techniques along with NMR and fluorescence microscopy. Moreover, we have explored the differential molecular recognition of 8-anilino-1-naphthalenesulfonic acid (ANS) and 2,6-p-toluidinonaphthalene sulfonate (TNS) by bovine pancreatic -chymotrypsin (CHT) upon interaction with genomic DNA. The correlation of the molecular recognition of the DNA and DNA-protein complexes with the hydration dynamics has been further exploited in our studies. In addition, we have developed functional nanoparticles/Quantum dots (QDs) that are covalently linked to biological molecules to detect the molecular interaction phenomenon between biomolecules. It should be noted that QDs have a significant contribution in the field of nano-biotechnology due to its high quantum yield, low photo-bleaching and increased biological application (cell labeling, in vivo imaging, gene delivery, sensing of fluorescence and molecular recognition). In this regard, we have exploited QDs as a potential energy donor/acceptor system and validated Forster resonance energy transfer (FRET) model over nano-surface energy transfer (NSET) technique. Therefore, the ultrafast non-radiative energy migration from tryptophan (Trp214) present in HSA to the HSA bound CdS QD, and fro
分子识别过程是指小配体分子与生物大分子之间选择性和特异性发生的弱非共价相互作用。了解生物和仿生环境中的这种识别是药物设计的核心吸引力,这对改善人类医疗保健至关重要。对决定这种分子相互作用的结构、动力学和能量参数的全面了解可以在配体-大分子识别过程的调节中找到巨大的用途。在这篇文章中,我们展示了我们持续的努力来研究涉及生物分子识别的基本物理过程,例如效率(结合亲和力和配合物的刚性)和溶剂分子在分子识别中的作用,使用稳态和主要是超快速时间分辨荧光光谱。从这个角度来看,我们已经彻底研究了小配体/药物分子的分子识别(利福平;射频,4 - (dicyanomethylene) 2-methyl-6 (p-dimethylaminostyryl) 4 h-pyran;DCM和尼罗河蓝;NB)通过人类转运蛋白,人血清白蛋白(HSA),并建立了配体分子(Rf)和仿生系统(十二烷基硫酸钠(SDS)胶束)之间的非特异性相互作用。插入剂(溴化乙啶,EtBr)和DNA小凹槽结合剂(Hoeschst 33258, H258)对特定序列的十二聚体DNA的同时识别也被监测到。此外,我们报道了利用上述光谱技术以及核磁共振和荧光显微镜研究了合成DNA和各种细胞核在兴奋剂咖啡因存在下对潜在诱变剂乙啶(Et)阳离子的识别。此外,我们还探索了牛胰腺-糜蛋白酶(CHT)在与基因组DNA相互作用时对8-苯胺-1-萘磺酸(ANS)和2,6-对甲苯基萘磺酸(TNS)的分子识别差异。DNA和DNA-蛋白复合物的分子识别与水合动力学的关系在我们的研究中得到了进一步的开发。此外,我们还开发了与生物分子共价连接的功能纳米粒子/量子点(QDs),用于检测生物分子之间的分子相互作用现象。值得注意的是,量子点由于其高量子产率、低光漂和越来越多的生物应用(细胞标记、体内成像、基因传递、荧光传感和分子识别),在纳米生物技术领域做出了重大贡献。在这方面,我们利用量子点作为潜在的能量供体/受体系统,并在纳米表面能量转移(NSET)技术上验证了福斯特共振能量转移(FRET)模型。因此,利用FRET技术研究了HSA中色氨酸(Trp214)向HSA结合的CdS QD的超快非辐射能量迁移,以及CHT中4-硝基苯基苯甲酸(NPA)向银(Ag)纳米团簇(NPA和Ag结合的CHT)的超快非辐射能量迁移,分别监测了HSA的蛋白质折叠途径以及NPA和CHT之间的分子相互作用。此外,我们还利用功能化量子点(CdSe/ZnS)检测了合成DNA对溴化乙啶(EtBr)的分子识别。本文就超快光谱技术在生物分子识别领域的研究进展进行综述,以期对纳米生物技术和医学领域的进一步研究具有潜在的意义
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引用次数: 1
Effect of Soy Protein Supplementation on Hepatic Lipid Profile in Rats Fed a Cholesterol-Based Diet 大豆蛋白补充对以胆固醇为基础的饮食大鼠肝脂质的影响
Pub Date : 2011-10-31 DOI: 10.15866/IREBIC.V2I5.1538
O. Oluba, F. Bamisaye, A. O. Olusola, A. O. Iyamu, G. Eidangbe
The effect of soy protein intake on liver lipid homeostasis in cholesterol-fed rats was investigated. One hundred and five albino Wistar rats divided into five groups (n = 21) were fed 20% soy protein without cholesterol (A), 20% soy protein + 5% cholesterol (B), 20% soy protein + 10% cholesterol (C), 0% soy protein + 20% cholesterol (D), and 5% soy protein + 20% cholesterol (E) for six weeks. Liver total cholesterol, esterified cholesterol, low density lipoprotein cholesterol and triglyceride levels were significantly reduced (p<0.05) in soy protein fed rats (B and C) when compared with those fed cholesterol with no or minimal soy protein (D and E) supplement respectively. It could thus be concluded that soy protein supplementation reduces hepatic lipid load in hypercholesterolemic rats
研究了大豆蛋白摄入对高胆固醇大鼠肝脏脂质稳态的影响。105只白化Wistar大鼠,分为5组(n = 21),分别饲喂不含胆固醇的20%大豆蛋白(A)、20%大豆蛋白+ 5%胆固醇(B)、20%大豆蛋白+ 10%胆固醇(C)、0%大豆蛋白+ 20%胆固醇(D)、5%大豆蛋白+ 20%胆固醇(E),为期6周。大豆蛋白喂养大鼠(B和C)的肝脏总胆固醇、酯化胆固醇、低密度脂蛋白胆固醇和甘油三酯水平均显著低于不添加或少量添加大豆蛋白(D和E)的大鼠(p<0.05)。由此可以得出结论,补充大豆蛋白可以降低高胆固醇血症大鼠的肝脏脂质负荷
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引用次数: 0
Quantum Chemical Analysis of Structural and Conformational Properties of Methisazone and Prototropic Tautomerism of Isatin 甲巯咪唑酮结构和构象性质的量子化学分析及Isatin的原向异变异构性
Pub Date : 2011-10-31 DOI: 10.15866/IREBIC.V2I5.1537
O. Bolsunova, O. Brovarets’, D. Hovorun, L. Zaika, A. Potopalsky
The conformational diversity of methisazone and prototropic molecular tautomerism of isatin were investigated by means of ab initio calculations at the MP2/6-311++G(2df,pd)//DFT B3LYP/6-311++G(d,p) level of theory. A comprehensive conformational, energetical and polar analysis of the methisazone (1-methyl-1H-indole-2,3-dione 3-thiosemicarbazone), a thiosemicarbazone, was provided. We established that flexibility of the thiosemicarbazone group causes conformational diversity of methisazone molecule. Structural, energetical and electron-topological characteristics of specific intramolecular contacts in methisazone conformers were analyzed. In general, two types of H-bonds (NH…O, CH…N), one type of dihydrogen bond (CH…HN) and three types of van der Waals contacts (N…N, N…O, C…O) were detected by performing electron density topological analysis for all 11 conformers of methisazone. A wide range of biological activity of izatizon based on conformational capacity of methisazone molecule, the main constituent part of this drug, was shortly discussed. Five molecular prototropic tautomers of isatin (1H-indole-2,3-dione) – one diketo and four enol tautomeric forms - were indicated. All five isomers have relative Gibbs free energies within a wide range of ~40 kcal∙mol−1 at physiological temperature. The possible biochemical role of tautomeric forms of isatin was briefly discussed
在MP2/6-311++G(2df,pd)//DFT / B3LYP/6-311++G(d,p)理论水平上,通过从头计算研究了甲巯咪唑酮的构象多样性和isatin的原向性分子互变异构性。本文对甲巯氨基脲(1-甲基- 1h -吲哚-2,3-二酮3-硫代氨基脲)进行了全面的构象、能量和极性分析。我们确定了硫代氨基脲基团的柔韧性导致了甲基咪唑酮分子的构象多样性。分析了甲基沙酮构象中特定分子内接触的结构、能量和电子拓扑特征。总体而言,通过对所有11种构象进行电子密度拓扑分析,检测到两种类型的氢键(NH…O, CH…N),一种类型的二氢键(CH…HN)和三种类型的范德华触点(N…N, N…O, C…O)。本文简要讨论了该药物的主要成分甲基沙酮分子的构象能力对其生物活性的影响。结果表明,isatin (1h -吲哚-2,3-二酮)的五种分子原生互变异构体-一种二酮和四种烯醇互变异构体。在生理温度下,这5种异构体的相对吉布斯自由能均在~40 kcal∙mol−1的范围内。简要讨论了isatin互变异构体形式可能的生化作用
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引用次数: 1
Self-Assembly of Amyloid Beta Peptide Over Dialkoxy Disulfide Functionalized Nano Gold Colloidal Particles 淀粉样肽在二氧基二硫化物功能化纳米金胶体粒子上的自组装
Pub Date : 2011-10-31 DOI: 10.15866/IREBIC.V2I5.1540
K. Yokoyama, Amy Tran, R. Priefer
Aiming to more stably produce an oligomer form of amyloid beta (i.e., a key intermediate of fibrillogenesis which eventually leads to Alzheimer’s disease), the surface of gold colloids were functionalized with nitro-, phenyl-, chloro-, and methoxy-dibenzyloxy disulfide, and molecular interactions were investigated in a dimethyl sulfoxide environment. The transition of color change was observed at pHo as the pH value was lowered externally. As evidence of disulfide being adsorbed on the colloidal surface, the pHo values were dependent of each substituent of the dibenzyloxy disulfide compounds. The trend of pHo exhibited a parabolic relationship as a function of F-value (Swain-Lupton Field constant). Functionalization of gold colloidal surface with methoxy-dibenzyloxy disulfide achieved larger amplitude in repetitive peak shift between pH 4 and 10 implying a formation of an oligomer under the reversible process
为了更稳定地产生低聚物形式的β淀粉样蛋白(即纤维形成的关键中间体,最终导致阿尔茨海默病),用硝基、苯基、氯基和甲氧基二硫化物对金胶体表面进行了功能化,并在二甲基亚砜环境中研究了分子相互作用。在pH值为pHo时,随着外部pH值的降低,观察到颜色变化的转变。作为二硫化物被吸附在胶体表面的证据,pHo值依赖于二苯氧基二硫化物化合物的每个取代基。pHo的变化趋势与f值(Swain-Lupton Field constant)呈抛物线关系。在pH值为4 ~ 10之间,甲氧基二苯氧基二硫化物对金胶体表面的功能化在重复峰移中获得了较大的振幅,表明在可逆过程下形成了低聚物
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引用次数: 1
Mapping surface heterogeneity: the AFM-based approach 映射表面异质性:基于afm的方法
Pub Date : 2011-10-31 DOI: 10.15866/IREBIC.V2I5.1541
James R. Smith, T. Nevell, J. Tsibouklis
In this short review, the use of maps is presented charting the surface distribution of the forces of adhesion, indentation and friction, as obtained with the atomic force microscope for the study of surface homogeneity. Phase-separated polymer blends are chosen as examples to demonstrate the complementarity of the method with the more usual topographical imaging approach. Consequent to recent advances towards the determination of surface energy at the sub-micrometre scale, the mapping of this property is now a realistic possibility
在这篇简短的综述中,使用原子力显微镜绘制附着力、压痕和摩擦力的表面分布图,以研究表面均匀性。以相分离聚合物共混物为例,说明了该方法与更常用的地形成像方法的互补性。由于最近在亚微米尺度的表面能测定方面取得了进展,这种性质的映射现在是一种现实的可能性
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引用次数: 0
Disease –Age- Correlated Oxidative Status of Patients with Hypertensive and Diabetic Co-Morbidity in Central Hospital, Benin City, Nigeria 尼日利亚贝宁市中心医院高血压和糖尿病合并症患者的疾病-年龄相关氧化状态
Pub Date : 2011-10-31 DOI: 10.15866/IREBIC.V2I5.1539
O. A. Iyamu, J. Anionye, E. Onyeneke, O. Oluba, Omon M. Oyakhire, O. Aigbe
The study was designed to compare oxidative status of sufferers of a co-morbidity of hypertension and diabetes mellitus who have clinical evidence of sustained well controlled blood sugar and blood pressure with that of apparently healthy controls and to see if the variation of this oxidative status with progression (age) of the co-morbidity differ from the observations in previous studies with sufferers of solitary hypertension or diabetes. Blood samples were collected from  co-morbidity sufferers (n = 42; 17 males and 25 females ) and 42 apparently healthy volunteers for the determination of plasma levels of two endogenous antioxidant enzymes  (superoxide dismutase, SOD, and catalase, CAT) as well as markers of oxidative damage (malondialdehyde, MDA, and erythrocyte osmotic fragility, EOF). Results obtained showed that the blood levels of both SOD and CAT decreased significantly (P<0.001) as age of co-morbidity increases. Also levels of blood MDA and EOF increased with age of co-morbidity (P<0.001). The variation of these indices with disease age was more statistically significant than that observed in earlier studies with solitary diabetes or hypertension. This study shows that oxidative damage is worse in sufferers of hypertensive and diabetic co-morbidity than in sufferers of solitary diabetes or hypertension
本研究的目的是比较有临床证据表明血糖和血压持续得到良好控制的高血压和糖尿病患者与明显健康的对照组的氧化状态,并观察氧化状态随合并疾病进展(年龄)的变化是否与以往对单纯性高血压或糖尿病患者的研究结果不同。采集合并症患者的血样(n = 42;17名男性和25名女性)和42名明显健康的志愿者测定血浆中两种内源性抗氧化酶(超氧化物歧化酶,SOD和过氧化氢酶,CAT)以及氧化损伤标志物(丙二醛,MDA和红细胞渗透脆性,EOF)的水平。结果显示,随着合并发病年龄的增加,血中SOD和CAT水平均显著降低(P<0.001)。血MDA和EOF水平也随合并发病年龄的增加而升高(P<0.001)。这些指标随疾病年龄的变化比早期研究中观察到的单纯性糖尿病或高血压更有统计学意义。本研究表明,高血压合并糖尿病患者的氧化损伤比单纯性糖尿病或高血压患者更严重
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引用次数: 0
Differential Binding Mode of a Phenanthroline-Based Metal Complex to a DNA or RNA Telomeric Sequence 邻菲罗啉金属配合物与DNA或RNA端粒序列的差异结合模式
Pub Date : 2011-08-31 DOI: 10.15866/IREBIC.V2I4.1529
C. Musetti, S. Bianco, A. Krapcho, M. Palumbo, C. Sissi
RNA G-quadruplexes have been recently proposed as physiologically relevant structures in cellular processes which suggests they represent attractive novel drug targets. Up-to-date, limited information of their interactions with small molecules is available. In particular, no systematic comparative analysis of the DNA vs RNA recognition processes has been performed. Here, we investigated the RNA G-quadruplex binding properties of a phenanthroline-based metal complex, (P115)Ni(II), known to efficiently recognize the DNA telomeric sequence. We showed that one ligand molecule can be sandwiched between two RNA G-quadruplex units. Conversely, this binding mode is not occurring using the DNA counterpart as the target sequence
RNA g -四联体最近被认为是细胞过程中的生理相关结构,这表明它们代表了有吸引力的新型药物靶点。它们与小分子相互作用的最新有限信息是可用的。特别是,没有对DNA和RNA识别过程进行系统的比较分析。在这里,我们研究了一种以菲罗啉为基础的金属配合物(P115)Ni(II)的RNA g -四重体结合特性,已知它能有效识别DNA端粒序列。我们发现一个配体分子可以夹在两个RNA g -四重体单元之间。相反,使用DNA对应物作为目标序列时,这种结合模式不会发生
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引用次数: 0
Effects of Protein Binding on DNA G-Quadruplex Structures 蛋白质结合对DNA g -四重结构的影响
Pub Date : 2011-08-30 DOI: 10.15866/IREBIC.V2I4.1524
S. Nagatoishi, D. Miyoshi, N. Sugimoto
The non-canonical G-quadruplex is a unique DNA structure that has received widespread attention because of its potential functions not only in vitro but also in vivo. The G-quadruplex is stabilized by formation of Hoogsteen hydrogen bonds in guanine quartets and involves cation coordination and dehydration. Although a number of proteins have been identified that specifically stabilize and destabilize G-quadruplexes, the effect of the protein binding remains unclear. Here, we review the behaviors of proteins binding to G-quadruplexes. We also discuss analyses of the thermodynamic and binding properties of G-quadruplexes in the complexes formed by histones and thrombins. These studies have helped us to understand the essential features of interaction between G-quadruplexes and proteins
非规范g -四重体是一种独特的DNA结构,由于其在体内和体外的潜在功能而受到广泛关注。g -四联体通过鸟嘌呤四合体中Hoogsteen氢键的形成而稳定,并涉及阳离子配位和脱水。虽然已经确定了一些蛋白质可以特异性地稳定和破坏g -四联体,但蛋白质结合的效果仍不清楚。在这里,我们回顾了蛋白质与g -四联体结合的行为。我们还讨论了组蛋白和凝血酶形成的复合物中g -四联体的热力学和结合性质的分析。这些研究帮助我们了解了g -四重复合物和蛋白质之间相互作用的基本特征
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引用次数: 0
Hit identification of anthraquinone based molecules as c-myc G-quadruplex inducers/stabilizers via in silico structural similarity approach 用硅结构相似性方法鉴定蒽醌类分子作为c-myc g -四重诱导剂/稳定剂
Pub Date : 2011-08-30 DOI: 10.15866/IREBIC.V2I4.1521
V. P. Ma, W. Lam, Dik‐Lung Ma, C. Leung
Natural products in Traditional Chinese Medicine (TCM) such as anthraquinone derivatives have a wide variety of pharmacological properties as well as proven record of high efficacy. Previously, our group reported an anthraquinone derivative Fonsecin B as c-myc G-quadruplex stabilizer. We herein report two bioactive anthraquinones with modifiable hydroxyl groups abundant in Chinese Medicine Rheum Palmatum L. (also known as Da Huang) as c-myc G-quadruplex stabilizer, identified by in silico structural similarity approach. Interaction of the anthraquinones with c-myc G-quadruplex was investigated by PCR Stop Assay
蒽醌衍生物等中药天然产物具有多种药理特性,并被证明具有很高的疗效。之前,我们的小组报道了蒽醌衍生物Fonsecin B作为c-myc - g四联稳定剂。本文报道了两种在中药材大黄中含有可修饰羟基的生物活性蒽醌,它们是c-myc g -四联体稳定剂,通过硅结构相似性方法进行了鉴定。用PCR停止法研究蒽醌类与c-myc g -四重体的相互作用
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引用次数: 0
期刊
International Review of Biophysical Chemistry
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