The origin of life

The theory of the evolution of the species, which is today widely accepted, requires a starting point. It is postulated that the biological starting point could have emerged only if chemical evolution had preceded it. Experiments are described which show the formation of organic substances from inorganic gases under conditions which prevailed on earth in the prebiotic era; also demonstrated is the polymerization of such organic substances into biological macromolecules. Hypotheses are discussed whereby these macromolecules could be transformed into dynamic structures which might finally lead to self-reproduction.     

Biochemistry and Molecular Biology of Snake Neurotoxin

A review of research on snake neurotoxin is presented, with emphasis on the chemical modification studies and molecular cloning of postsynaptic and presynaptic neurotoxins from Naja naja atra (Taiwan cobra) (Fig. 1a) and Bungarus multicinctus (Taiwan banded krait) (Fig. 1b). Cobrotoxin and α-bungarotoxin are the primary postsynaptic neurotoxins isolated from the venom of N. naja atra and B. multicinctus, respectively. Although they share a common three-dimensional structure, the functional elements essential for the manifestation of their toxicity are different. Selective and stepwise chemical modification of cobrotoxin indicate that at least two cationic groups, an ?-amino group of Lys-47 and a guanidino group of Arg-33 common to all known postsynaptic neurotoxins, are functionally important for its neuromuscular blocking activity. However, for α-bungarotoxin, the side chains of several basic amino acid residues are involved in the multipoint contact between the toxin and acetylcholine receptor. Moreover, the conserved Trp residue is essential for the neurotoxicity of cobrotoxin, but not for α-bungarotoxin. The cDNAs encoding cobrotoxin and α-bungarotoxin was constructed from the cellular RNA isolated from the venom glands of N. naja atra and B. multicinctus by polymerase chain reaction. The sequence of their 3′-untranslational region, signal peptide and 5′-untranslational region share a high degree of homology, suggesting that they are evolutionarily related. Expression of both neurotoxic protein in E. coli generated polypeptide chains for reactions with the antisera against the native neurotoxins. Presynaptic neurotoxins constitute a different group of neurotoxic proteins in snake venom proteins. These presynaptic neurotoxins are either basic phospholipase A₂ (PLA₂) per se or contain basic PLA₂ as an indispensible part of their structures. Thus, the presynaptic neurotoxins usually show both PLA₂ activity and presynaptic neurotoxicity. β-Bungarotoxin (β-Bgt), the main presynaptic PLA₂ neurotoxin isolated from the venom of B. multicinctus (Taiwan banded krait), consists of two dissimilar polypeptide chains, a PLA₂ subunit (A chain) and potassium channel recognition subunit (B chain). Chemical modification studies show that the toxin might possess two functional sites, one responsible for the catalytic activity and the other for its pharmacological properties. Molecular cloning and expression of the A chain and B chain of β-Bgt reveal that the A chain of β-Bgt is an active subunit with PLA₂ activity, and that the B chain is involved in voltage-gated potassium channel blocking action observed with β-Bgt.     

化学生物学中识别与组装的若干问题

化学与生物学的交叉与融合产生了新学科——化学生物学,开拓了化学和生物学研究的新领域,使人类得以从分子水平来阐释生命过程,揭示生命的奥秘。分子识别和组装是体系的构筑与功能集成的基础,也是自然界生物进行信息存贮、复制和传递的基础,以此来研究构筑具有特定生物学功能的超分子体系,对揭示生命现象和过程具有重要意义。本文结合我们的研究工作从（1）谷胱甘肽过氧化物酶(GPX)模拟与底物识别;（2）医用再生材料与活性支架;（3）类病毒颗粒的组装与解组装3个方面讨论了化学生物学中的识别与组装的意义。     

Molecular evolution of the plant ECERIFERUM1 and ECERIFERUM3 genes involved in aliphatic hydrocarbon production

The Arabidopsis ECERIFERUM1 (CER1) protein is a decarbonylase that converts fatty acid metabolites into alkanes. Alkanes are components of waxes in the plant cuticle, a waterproof barrier serving to protect land plants from both biotic and abiotic stimuli. CER1 enzymes can be used to produce alternative and sustainable hydrocarbons in eukaryotic systems. In this report we identified 193 CER1 and 128 CER3 sequences from 56 land plants respectively. CER1 and CER3 proteins have high amino acid similarity and both are involved in alkane synthesis in Arabidopsis. The common homologues of CER1 and CER3 genes were identified in three species of chlorophytes, which may be one of the earliest plant taxa that possess CER1 and CER3 genes. To facilitate potential applications, the 3-dimensional structure and conserved motifs of CER1 proteins were also characterized. CER1 and CER3 proteins are structurally similar, but CER1 proteins have more conserved histidine-containing motifs common to fatty acid hydroxylases and stearoyl-CoA desaturases. There was no significant loss or gain of protein motifs after ancient and recent duplications, suggesting that varied properties of CER1 proteins may be associated with less-conserved regions. Among 56 land plants, the codon-based assessments of selection modes revealed that neither entire proteins nor individual amino acids of CER1 proteins were significantly subjected to positive selection, indicating that CER1 proteins are highly conserved throughout evolution.     

Chemistry and Molecular Biology of Transmissible Spongiform Encephalopathies

Prion diseases are currently in the spotlight. Among them, the Creutzfeldt–Jakob disease in humans, scrapie in sheep, and bovine spongiform encephalopathy, or mad cow disease, are most commonly known. The term “spongiform” refers to the characteristic appearance of the lesions found in affected brains. It is likely that prion diseases originate from a causative agent that replicates independently of nucleic acids. Current research assumes that a structural isoform of prion protein, the scrapie form PrP^Sc, is the responsible pathogen. The three-dimensional structure, but not the amino acid sequence of the isoform differs from that of the normal cellular isoform, PrP^c. According to a widely accepted hypothesis, the normal isoform of the protein is converted by an autocatalytic process into the scrapie form upon contact with the latter. This hypothesis has not yet been proven. However, considerable progress has been made in the last few years, which might provide answers to many open questions about prion diseases, the subject of this review.     

Molecular Chirality in Chemistry and Biology: Historical Milestones

Beginning early in the 19th century, developments in crystallography, optics, and chemistry in France set the stage for the discovery of molecular chirality by Louis Pasteur in 1848. He found that the crystallization of the sodium ammonium salt of ‘paratartaric acid’, a mysterious ‘isomer’ of natural (+)‐tartaric acid (TA), produced two different crystal types that were non‐superimposable mirror‐image forms of each other. He separated the two types and found their optical rotations in solution opposite in direction and equal in absolute magnitude. This led him to conclude that paratartaric acid is a combination of two mirror‐image molecule types of TA that are ‘dissymmetric’, an existing term he adapted to the connotation of today's ‘chiral’. In 1857, he found that the two enantiomers of TA were metabolized by a microorganism at drastically different rates, and thereby discovered biological enantioselectivity. In 1886, Italian chemist Arnaldo Piutti discovered D ‐asparagine and found that it tasted intensely sweet, in contrast to the known L ‐asparagine which had no taste. This was the discovery of stereoselectivity at biological receptors. As a result of advances in stereoselective synthesis and enantioselective chromatography during the last decades of the 20th century, in the 1990s the importance of molecular chirality in drug action and disposition began to receive serious attention from drug‐regulatory authorities and the pharmaceutical industry, the overall result of which has been the near‐complete disappearance of racemic drugs as newly introduced pharmaceuticals.     

Replication and Evolution in Inorganic Systems

Using layer silicates as models, the principle of replication, i.e. the spontaneous self-multiplication of a carrier of information, can be shown to be a general property of certain macromolecular systems. Errors in replication and feedback together with environmental influences may lead to mutants with higher or lower replication rates, thus enabling evolution. In the light of these findings, the question of whether or not chemical evolution resulted directly in the nucleic acid/protein system, i.e. the genetic principle common to all living systems known up to now, has to be answered. It seems conceivable that as a first step a much simpler replicating system was formed: such a system might then have undergone an evolution of replicating systems, resulting in the final nucleic acid/protein system.     

Asymmetry in the Multiprotein Systems of Molecular Biology

Signaling in living systems needs to achieve high specificity, to be reversible, and to achieve high signal to noise. Signaling mediated by multiprotein systems has evolved that avoids the requirement for high-affinity binary complexes that would be difficult to reverse and which, in the overcrowded cell, would lead to excessive noise in the system. Symmetrical structures are only occasionally formed. When they are, it is principally to colocate components, for example, the tyrosyl kinases of growth factors, where dimers form. Symmetry is, however, often broken, presumably to create more sensitivity and specificity in the signaling system by assembling other components, into higher-order multiprotein systems. The binding of a single heparin to two 1:1 FGF:FGFR complexes is an example, as is the binding of a single ligase to the Xrcc4 dimer, perhaps so creating a further DNA-binding site.     

硒蛋白的分子生物学及与疾病的关系*

硒蛋白是微量元素硒在体内存在和发挥生物功能的主要形式。因硒蛋白的活性中心硒代半胱氨酸由传统终止码TGA编码,故从基因组中预测硒蛋白以及用基因工程技术表达硒蛋白均很困难。有关硒抗氧化、对癌症、神经退行性疾病和病毒作用的报导较多,但结论并不一致。本文综述了硒蛋白基因预测、蛋白质表达调控以及硒和硒蛋白对癌症、神经退行性疾病和病毒的作用及机制等方面的近期进展,研究提高硒蛋白生物信息学预测准确率和基因工程表达量的方法,分析了解硒蛋白与疾病发生发展的关系和机制,探索不同硒蛋白作为预防药物开发、作为癌症治疗和药物筛选靶标的可能性。     

Chemistry and Molecular Biology in the Search for New LHRH Antagonists

Hormones—and in particular, the sex hormones—were the first growth factors discovered to be involuntary helpers of cancer. Female breast cancer and male prostate cancer are the best known examples of tumors acknowledged to be hormone-dependent. A look at cancer statistics shows that breast cancer is still the most frequent cancer in women; in men, prostate cancer plays a similarly dominant role with increasing age. Shutting down the main production site of the sex hormones estrogen and testosterone either by removing the ovaries or by castration is a well-known and often effective therapy; however, these procedures can be problematic due to the concomittant psychological stress. Modern hormone therapy for advanced breast cancer and prostate cancer attempts to spare the patient such irreversible operative procedures for as long as possible, by using hormone antagonists, such as the LHRH antagonists, which hinder deployment of the hormone itself and thus its growth-promoting activity.     

Chemical Biology Studies on Molecular Diversity of Annonaceous Acetogenins

Annonaceous acetogenins, isolated from the Annonaceae plants, have been attracting worldwide attention in recent years due to their biological activities, especially as growth inhibitors of certain tumor ceils [ 1 ]. They have been shown to function by blocking complex I in mitochondria [2] as well as ubiquinone-linked NADPH oxidase in the cells of specific tumor cell lines, including some multidrug-resistant ones [3]. These features make these acetogenins excellent leads for the new antitumor agents. In our previous work, the compounds 1a to 1d (Figure 1), which relies on structure simplification while maintaining all essential functionalities of the acetogenins, was in vitro tested against several human solid tumor cell lines and showed interesting cell selectivity [4]. All four analogues show remarkable activity against the HCT-8 and HT-29 cell lines, while compound 1c was found the best [4bi. In order to further investigate the effects of key structural features, a convergent parallel fragments assembly strategy was developed [4e]. In addition, the biological relevancies of typical annonaceous acetogenin mimetics were also studied [4f].     

Self-Healing Molecular Biology for Microbial Concrete: A Review

The most extensively utilized material in construction is concrete, decreasing life of structure pointing toward loses in structural health. The crack is the major problem faced in the concrete construction. This causes the corrosion in the steel reinforcement. The structure gets deteriorated with the developing cracks; therefore need the proper attention toward this problem. The present work consists of the different self-healing techniques used by the researchers to inhibit the crack and prevent further deterioration in the structure. The self-healing mechanism proves advantageous in use of natural fibers to inhibit the corrosion process, to increase compressive strength, and to decrease water absorption is present in this study. The maximum strength increased and the width of crack get healed with the help of these techniques is also mentioned in the study.     

Glycosylated Nanoscale Surfaces: Preparation and Applications in Medicine and Molecular Biology

Carbohydrates on cell surfaces are critical components of the extracellular landscape and contribute to cell signalling, motility, adhesion and recognition. Multivalent effects are essential to these interactions that are inherently weak. Carbohydrate‐functionalised surfaces meet an important need for studying the multivalent interactions between carbohydrates and other biomolecules. Innovations in nanomaterials are revolutionising how these carbohydrate interfaces are studied and underscore their importance in the cosmos of biochemical interactions.     

利用微生物直接生产羟基丁酸单体

利用重组大肠杆菌E.coli HB101来进行直接生产羟基丁酸(HB)手性单体,研究了含pUCAB质粒的重组体E.coli HB101在各种条件下生长及积累HB单体的情况,研究了HB单体的积累随pH值变化的规律。结果表明,pH=6.8时,48 h内细菌可生产0.5 g/L以上的HB单体。     

Atomic-Resolution Experimental Structural Biology and Molecular Dynamics Simulations of Hyaluronan and Its Complexes

This review summarizes the atomic-resolution structural biology of hyaluronan and its complexes available in the Protein Data Bank, as well as published studies of atomic-resolution explicit-solvent molecular dynamics simulations on these and other hyaluronan and hyaluronan-containing systems. Advances in accurate molecular mechanics force fields, simulation methods and software, and computer hardware have supported a recent flourish in such simulations, such that the simulation publications now outnumber the structural biology publications by an order of magnitude. In addition to supplementing the experimental structural biology with computed dynamic and thermodynamic information, the molecular dynamics studies provide a wealth of atomic-resolution information on hyaluronan-containing systems for which there is no atomic-resolution structural biology either available or possible. Examples of these summarized in this review include hyaluronan pairing with other hyaluronan molecules and glycosaminoglycans, with ions, with proteins and peptides, with lipids, and with drugs and drug-like molecules. Despite limitations imposed by present-day computing resources on system size and simulation timescale, atomic-resolution explicit-solvent molecular dynamics simulations have been able to contribute significant insight into hyaluronan’s flexibility and capacity for intra- and intermolecular non-covalent interactions.     

Small Organic Molecular Electrocatalysts for Fuels Production

In recent years, heterocyclic organic compounds have been explored as molecular electrocatalysts in relevant reactions for energy conversion and storage. Merging mimetics of biological systems that perform hydride transfer with rational synthetic chemical design has opened many opportunities for organic molecules to be tuned at the atomic level conferring them interesting reactivities. These molecular electrocatalysts represent an alternative to traditional metallic materials and metal complexes employed for water oxidation, hydrogen production, and carbon dioxide reduction. This minireview describes recent reports concerning design, catalytic activity and the mechanism of synthetic molecular electrocatalysts towards solar fuels production.