降血糖中药及有效成分的研究进展

本文通过PrloQuest Medical Library和中国学术期刊教据库,对降血糖中药有效成分等设置关键词检索,综述了1994年以来国内外降血糖中药有效成分及研究现状.具有降血糖作用的中药化学成分主要包括多糖、生物碱、黄酮、皂苷、萜及含硫化合物等六大类,虽然各类中药成分的有效性及其作用机理迥异,但其研究进展,为降血糖的分子中药研究开发奠定了良好基础.降血糖中药有效成分是重要的降血糖中药分子,进一步研究和探讨这些中药分子的中药药性和组方配伍规律,对于创制高效低毒的降血糖分子中药,推进中药现代化具有重要理论和实践指导意义.     

黏附分子在肿瘤发生及发展中的作用

细胞黏附分子是以配体和受体相结合的形式,介导细胞与细胞间或细胞与基质间相互作用的一类分子,参与机体的多种重要生理和病理过程.近年来,在对肿瘤发生和发展的研究中发现,黏附分子可通过多种途径影响肿瘤的生长、浸润及转移过程.因此.对黏附分子在肿瘤发生和发展中作用及机制的深入研究,可为肿瘤早期诊断提供重要的分子指标和发现新的治疗靶标.并为进而形成临床诊疗新策略提供重要理论支持.现就几种重要黏附分子在肿瘤生长与转移中的作用进行综述.     

科学快讯

200年度中国基础研究十大新闻评选揭晓;十一五期间将新建30个国家实验室;你的大脑如何知道时间;细胞内微管利用蛋白贡作为分子发动机和刹车片以组建他们正确的结构;《Science》根据再生能力有望重划身体器官分类。     

蜘蛛分子系统学研究进展

蜘蛛是地球上最古老和物种最丰富的生物类群之一,有化石记录最早可追溯至泥盆纪(距今约三亿八百万年).对蜘蛛的系统学研究长期以传统的形态分类为主,随着分子生物学技术的发展,蜘蛛分子系统学研究也取得了长足进展:部分类群依据分子数据或分子结合形态的系统发育关系得以解决,并建立了相应的系统发育树; 所选择的分子标记除来自于线粒体DNA外(如:COI、12S rDNA和16S rDNA等)还有核DNA(如:18S rDNA、28S rDNA和Hitone 3等); 最新的分析方法和分析软件也得到运用.这些工作为蜘蛛的生命之树研究奠定了重要基础.本文对蜘蛛分子系统学研究所涉及到的问题进行了分析讨论,以期为蜘蛛分子系统学的深入开展提供基础资料.     

植物分子系统学近五年的研究进展概况

本文综述了与分子系统学发展密切相关的4个因素：1.分子生物学方法的不断改进;2.基因组的全序列测定;3.用于分子系统学研究的基因种类不断增加,对这些基因进化规律的认识不断深入;4.化石DNA的研究。本文还阐述了核基因及叶绿体基因在系统学研究中的应用,例举了rbcL、matk、18s rDNA和ITS序列分析在植物系统发育研究中取得的重要成果,同时提出了分子系统学研究中应注意的一些问题。     

生物分子自组装

分子自组装是一种普遍存在于生命体系中的现象,是生命科学最本质的内容之一。开展分子自组装的研究具有重要意义,有助于人们从分子水平上认识自然界中生命形成和演变的过程,并为人们提供新的思路,开展生物医学基础研究、新材料合成及分子器件研制等。该文介绍了自组装的基本含义,对分子自组装技术在生物材料、生物分子器件研究方面的进展作了综述。     

分子动态模拟及其在生物大分子研究中的应用

生物分子动念模拟技术是运用计算机对生物大分子的结构、功能、质子运动轨迹以及生物分子间的相互作用进行预测,是研究生物分子结构和功能的重要手段.该文介绍分子动态技术的原理及其在生命科学研究中的应用和研究进展,分析目前存在的问题,并提出对未来工作的展望.     

分子伴侣及其在蛋白质折叠中的作用研究进展

蛋白质折叠是一个复杂的、动态的过程,蛋白质的折叠不是自发的,需要其他物质的帮助.了解分子伴侣在蛋白质折叠过程中的的作用,有助于进一步研究蛋白质折叠机制.本文介绍了分子伴侣及其分类,重点综述了各类分子伴侣在蛋白质折叠中的机制,并提出了研究分子伴侣在蛋白质折叠中的作用的重要意义.     

分子伴侣HdeA与底物蛋白SurA作用机制的模拟研究

分子伴侣HdeA与底物蛋白间的相互作用可帮助底物蛋白复性,这是肠道致病菌得以在酸性环境中幸存的重要原因之一.为探究HdeA发挥伴侣活性的作用机制,本研究采用分子对接和分子动力学的方法,模拟了HdeA与底物蛋白SurA间的相互作用,计算了二者的结合自由能.通过分析HdeA-SurA复合物体系的作用模式、氢键作用以及能量分解的结果,确定了HdeA与底物蛋白SurA结合时发挥重要作用的关键氨基酸残基.该研究结果为以后采用实验手段探究HdeA与底物蛋白之间的作用提供了重要的理论参考,同时为今后设计与开发HdeA的抑制剂提供了理论指导依据.     

蛋白质分子表面高质量网格构建技术的研究进展

分子表面即分子边界,在一定程度上蕴含了分子的生物化学属性信息,对分子表面进行分析将有助于理解分子对接、识别和相互作用等问题。由于蛋白质分子表面的构造相对复杂,尤其是分子表面的网格化,因此寻求高效的算法构建高质量的蛋白质分子表面网格对生成光滑的分子表面、分子可视化及分子模拟都有着重要的意义。本文主要根据现有定义的蛋白质分子表面,针对近年来几种高质量分子表面网格构建的新技术进行了阐述,同时介绍了几款蛋白质分子表面可视化软件,并对它们的性能进行了简单的分析。     

Rotary DNA motors.

Many molecular motors move unidirectionally along a DNA strand powered by nucleotide hydrolysis. These motors are multimeric ATPases with more than one hydrolysis site. We present here a model for how these motors generate the requisite force to process along their DNA track. This novel mechanism for force generation is based on a fluctuating electrostatic field driven by nucleotide hydrolysis. We apply the principle to explain the motion of certain DNA helicases and the portal protein, the motor that bacteriophages use to pump the genome into their capsids. The motor can reverse its direction without reversing the polarity of its electrostatic field, that is, without major structural modifications of the protein. We also show that the motor can be driven by an ion gradient; thus the mechanism may apply as well to the bacterial flagellar motor and to ATP synthase.     

Mitotic dynamics

A new model for mitotic dynamics of eukaryotic cells is proposed. In the kinetochore mo-tor-midzone motor model two kinds of motors, the kinetochore motors and the midzone motors, play important roles in chromosome movement. Using this model the chromosome congression during prometaphase, the chromosome oscillation during metaphase and the chromatid segregation during anaphase are described in a unified way.     

Common mechanisms of DNA translocation motors in bacteria and viruses using one-way revolution mechanism without rotation

Biomotors were once described into two categories: linear motor and rotation motor. Recently, a third type of biomotor with revolution mechanism without rotation has been discovered. By analogy, rotation resembles the Earth rotating on its axis in a complete cycle every 24 h, while revolution resembles the Earth revolving around the Sun one circle per 365 days (see animations http://nanobio.uky.edu/movie.html). The action of revolution that enables a motor free of coiling and torque has solved many puzzles and debates that have occurred throughout the history of viral DNA packaging motor studies. It also settles the discrepancies concerning the structure, stoichiometry, and functioning of DNA translocation motors. This review uses bacteriophages Phi29, HK97, SPP1, P22, T4, and T7 as well as bacterial DNA translocase FtsK and SpoIIIE or the large eukaryotic dsDNA viruses such as mimivirus and vaccinia virus as examples to elucidate the puzzles. These motors use ATPase, some of which have been confirmed to be a hexamer, to revolve around the dsDNA sequentially. ATP binding induces conformational change and possibly an entropy alteration in ATPase to a high affinity toward dsDNA; but ATP hydrolysis triggers another entropic and conformational change in ATPase to a low affinity for DNA, by which dsDNA is pushed toward an adjacent ATPase subunit. The rotation and revolution mechanisms can be distinguished by the size of channel: the channels of rotation motors are equal to or smaller than 2 nm, that is the size of dsDNA, whereas channels of revolution motors are larger than 3 nm. Rotation motors use parallel threads to operate with a right-handed channel, while revolution motors use a left-handed channel to drive the right-handed DNA in an anti-chiral arrangement. Coordination of several vector factors in the same direction makes viral DNA-packaging motors unusually powerful and effective. Revolution mechanism that avoids DNA coiling in translocating the lengthy genomic dsDNA helix could be advantageous for cell replication such as bacterial binary fission and cell mitosis without the need for topoisomerase or helicase to consume additional energy.     

Grip it and rip it: Structural mechanisms of DNA helicase substrate binding and unwinding

Maintenance and faithful transmission of genomic information depends on the efficient execution of numerous DNA replication, recombination, and repair pathways. Many of the enzymes that catalyze steps within these pathways require access to sequence information that is buried in the interior of the DNA double helix, which makes DNA unwinding an essential cellular reaction. The unwinding process is mediated by specialized molecular motors called DNA helicases that couple the chemical energy derived from nucleoside triphosphate hydrolysis to the otherwise non‐spontaneous unwinding reaction. An impressive number of high‐resolution helicase structures are now available that, together with equally important mechanistic studies, have begun to define the features that allow this class of enzymes to function as molecular motors. In this review, we explore the structural features within DNA helicases that are used to bind and unwind DNA. We focus in particular on “aromatic‐rich loops” that allow some helicases to couple single‐stranded DNA binding to ATP hydrolysis and “wedge/pin” elements that provide mechanical tools for DNA strand separation when connected to translocating motor domains.     

Single-molecule studies of nucleic acid motors

Nucleic acid motors comprise a variety of structurally, mechanistically and functionally very different enzymes. These motor proteins have in common the ability to directionally move DNA or RNA, or to move along DNA or RNA using a chemical energy source such as ATP. Recently, it became possible to study the action of a single motor on single DNA or RNA molecules in real time; this has provided unprecedented insight into the behavior and mechanism of these motors. As a result, the past few years have witnessed an enormous increase in such single-molecule studies of a variety of different motor systems. Particular highlights have included the investigation of the sequence-dependent behavior and helical tracking of motors, and the attainment of the ultimate (i.e. single base pair) resolution, which enables the detection of individual single base motor steps.     

Characterization of the Mycobacterial AdnAB DNA Motor Provides Insights into the Evolution of Bacterial Motor-Nuclease Machines

Mycobacterial AdnAB exemplifies a family of heterodimeric motor-nucleases involved in processing DNA double strand breaks (DSBs). The AdnA and AdnB subunits are each composed of an N-terminal UvrD-like motor domain and a C-terminal RecB-like nuclease module. Here we conducted a biochemical characterization of the AdnAB motor, using a nuclease-inactivated heterodimer. AdnAB is a vigorous single strand DNA (ssDNA)-dependent ATPase (k_cat 415 s⁻¹), and the affinity of the motor for the ssDNA cofactor increases 140-fold as DNA length is extended from 12 to 44 nucleotides. Using a streptavidin displacement assay, we demonstrate that AdnAB is a 3′ → 5′ translocase on ssDNA. AdnAB binds stably to DSB ends. In the presence of ATP, the motor unwinds the DNA duplex without requiring an ssDNA loading strand. We integrate these findings into a model of DSB unwinding in which the “leading” AdnB and “lagging” AdnA motor domains track in tandem, 3′ to 5′, along the same DNA single strand. This contrasts with RecBCD, in which the RecB and RecD motors track in parallel along the two separated DNA single strands. The effects of 5′ and 3′ terminal obstacles on ssDNA cleavage by wild-type AdnAB suggest that the AdnA nuclease receives and processes the displaced 5′ strand, while the AdnB nuclease cleaves the displaced 3′ strand. We present evidence that the distinctive “molecular ruler” function of the ATP-dependent single strand DNase, whereby AdnAB measures the distance from the 5′-end to the sites of incision, reflects directional pumping of the ssDNA through the AdnAB motor into the AdnB nuclease. These and other findings suggest a scenario for the descent of the RecBCD- and AddAB-type DSB-processing machines from an ancestral AdnAB-like enzyme.     

Measurements of single DNA molecule packaging dynamics in bacteriophage lambda reveal high forces, high motor processivity, and capsid transformations

Molecular motors drive genome packaging into preformed procapsids in many double-stranded (ds)DNA viruses. Here, we present optical tweezers measurements of single DNA molecule packaging in bacteriophage lambda. DNA-gpA-gpNu1 complexes were assembled with recombinant gpA and gpNu1 proteins and tethered to microspheres, and procapsids were attached to separate microspheres. DNA binding and initiation of packaging were observed within a few seconds of bringing these microspheres into proximity in the presence of ATP. The motor was observed to generate greater than 50 picoNewtons (pN) of force, in the same range as observed with bacteriophage phi29, suggesting that high force generation is a common property of viral packaging motors. However, at low capsid filling the packaging rate averaged approximately 600 bp/s, which is 3.5-fold higher than phi29, and the motor processivity was also threefold higher, with less than one slip per genome length translocated. The packaging rate slowed significantly with increasing capsid filling, indicating a buildup of internal force reaching 14 pN at 86% packaging, in good agreement with the force driving DNA ejection measured in osmotic pressure experiments and calculated theoretically. Taken together, these experiments show that the internal force that builds during packaging is largely available to drive subsequent DNA ejection. In addition, we observed an 80 bp/s dip in the average packaging rate at 30% packaging, suggesting that procapsid expansion occurs at this point following the buildup of an average of 4 pN of internal force. In experiments with a DNA construct longer than the wild-type genome, a sudden acceleration in packaging rate was observed above 90% packaging, and much greater than 100% of the genome length was translocated, suggesting that internal force can rupture the immature procapsid, which lacks an accessory protein (gpD).     

Na+-driven bacterial flagellar motors

Bacterial flagellar motors are the reversible rotary engine which propels the cell by rotating a helical flagellar filament as a screw propeller. The motors are embedded in the cytoplasmic membrane, and the energy for rotation is supplied by the electrochemical potential of specific ions across the membrane. Thus, the analysis of motor rotation at the molecular level is linked to an understanding of how the living system converts chemical energy into mechanical work. Based on the coupling ions, the motors are divided into two types; one is the H⁺-driven type found in neutrophiles such asBacillus subtilis andEscherichia coli and the other is the Na⁺-driven type found in alkalophilicBacillus and marineVibrio. In this review, we summarize the current status of research on the rotation mechanism of the Na⁺-driven flagellar motors, which introduces several new aspects in the analysis.     

The nonlinear chemo-mechanic coupled dynamics of the F 1 -ATPase molecular motor

The ATP synthase consists of two opposing rotary motors, F₀ and F₁, coupled to each other. When the F₁ motor is not coupled to the F₀ motor, it can work in the direction hydrolyzing ATP, as a nanomotor called F₁-ATPase. It has been reported that the stiffness of the protein varies nonlinearly with increasing load. The nonlinearity has an important effect on the rotating rate of the F₁-ATPase. Here, considering the nonlinearity of the γ shaft stiffness for the F₁-ATPase, a nonlinear chemo-mechanical coupled dynamic model of F₁ motor is proposed. Nonlinear vibration frequencies of the γ shaft and their changes along with the system parameters are investigated. The nonlinear stochastic response of the elastic γ shaft to thermal excitation is analyzed. The results show that the stiffness nonlinearity of the γ shaft causes an increase of the vibration frequency for the F₁ motor, which increases the motor’s rotation rate. When the concentration of ATP is relatively high and the load torque is small, the effects of the stiffness nonlinearity on the rotating rates of the F₁ motor are obvious and should be considered. These results are useful for improving calculation of the rotating rate for the F₁ motor and provide insight about the stochastic wave mechanics of F₁-ATPase.