Molecular mimicry--hypothesis or reality?

A number of observations support molecular mimicry as a possible pathogenetic mechanism in diseases such as acute rheumatic fever, reactive arthritis after enteric infection or associated with Reiter''s syndrome, myasthenia gravis, or even in rheumatoid arthritis. Molecular mimicry can be defined as a sharing of epitopes in linear or 3-dimensional presentation on disparate proteins from entirely different sources--for instance, group A streptococcal membranes and human cardiac myosin. How exposure to or infection with organisms sharing molecular similarity with antigens of the human host can evade tolerance and actually induce a self-reacting humoral or cellular immune response is still not clear; however, a large body of evidence has now been accumulated that documents apparent molecular mimicry mechanisms in these disorders. In some diseases, the molecular mimicry appears to involve human target organs and specific components of the infectious organism, whereas in others the host HLA cell surface molecules appear to share antigens with presumed bacterial or viral initiators of disease.     

Molecular Farming – OECD Workshop

Transgenic Research -     

Conformations of Higher Gangliosides and Their Binding with Cholera Toxin—Investigation by Molecular Modeling,Molecular Mechanics,and Molecular Dynamics

Abstract

Molecular mechanics and molecular dynamics studies are performed to investigate the conformational preference of cell surface higher gangliosides (GT1A and GT1B) and their interaction with Cholera Toxin. The water mediated hydrogen bonding network exists between sugar residues in gangliosides. An integrated molecular modeling, molecular mechanics, and molecular dynamics calculation of cholera toxin complexed with GT1A and GT1B reveal that, the active site of cholera toxin can accommodate these higher gangliosides. Direct and water mediated hydrogen bonding interactions stabilize these binding modes and play an essential role in defining the order of specificity for different higher ganglioside towards cholera toxin. This study identifies that the binding site of cholera toxin is shallow and can accommodate a maximum of two NeuNAc residues. The NeuNAc binding site of cholera toxin may be crucial for the design of inhibitors that can prevent the infection of cholera.     

Monosialogangliosides and Their Interaction with Cholera Toxin—Investigation by Molecular Modeling and Molecular Mechanics

Abstract

Molecular mechanics and molecular dynamics studies are performed to investigate the conformational preference of cell surface monosialogangliosides (GM3, GM2 and GM1) in aqueous environment. Water mediated hydrogen bonding network plays a significant role in the structural stabilization of GM3, GM2 and GM1. The spatial flexibility of NeuNAc of gangliosides at the binding site of cholera toxin reveals a limited allowed eulerian space of 2.4% with a much less allowed eulerian space (1.4%) for external galactose of GM1. The molecular mechanics of monosialoganglioside-cholera toxin complex reveals that cholera toxin can accommodate the monosialogangliosides in three different modes. Direct and water mediated hydrogen bonding interactions stabilize these binding modes and play an essential role in defining the order of specificity for different monosialogangliosides towards cholera toxin. This study identifies the NeuNAc binding site as a site for design of inhibitors that can restrict the pathogenic activity of cholera toxin.     

Molecular mechanisms of α-synuclein neurodegeneration

α-Synuclein is an abundant highly charged protein that is normally predominantly localized around synaptic vesicles in presynaptic terminals. Although the function of this protein is still ill-defined, genetic studies have demonstrated that point mutations or genetic alteration (duplications or triplications) that increase the number of copies of the α-synuclein (SCNA) gene can cause Parkinson's disease or the related disorder dementia with Lewy bodies. α-Synuclein can aberrantly polymerize into fibrils with typical amyloid properties, and these fibrils are the major component of many types of pathological inclusions, including Lewy bodies, which are associated with neurodegenerative diseases, such as Parkinson's disease. Although there is substantial evidence supporting the toxic nature of α-synuclein inclusions, other modes of toxicity such as oligomers have been proposed. In this review, some of the evidence for the different mechanisms of α-synuclein toxicity is presented and discussed.     

Molecular biology of β-lactam acylases

-Lactam acylases such as penicillin G acylases, penicillin V acylases and glutaryl 7-aminocephalosporanic acid acylases are used in the manufacture of 6-aminopenicillanic acid, 7-aminodesacetoxycephalosporanic acid and 7-aminocephalosporanic acid (7-ACA). Genetically-engineered strains producing 1050 U/g, 3200 U/g and 7000 to 10,000 U/I of penicillin G acylase, penicillin V acylase and glutaryl-7-ACA acylase, respectively, have been developed. The penicillin G acylase studied to date and the glutaryl-7-ACA acylase from Pseudomonas sp. share some common features: the active enzyme molecules are composed of two dissimilar subunits that are generated from respective precursor polypeptide; the proteolytic processing is a post-translational modification which is regulated by temperature; and the Ser residue at the N-terminus of the -sub-unit (Ser²⁹⁰; penicillin G acylase numbering) is implicated as the active site residue. Protein engineering, to generate penicillin G acylase molecules and their precursors with altered sequences, and the structure-function correlation of the engineered molecules are discussed.The authors are with Research and Development, Hindustan Antibiotics Ltd, Pimpri, Pune 411 018, India;     

Molecular parity violation via comets?

Recent theoretical and experimental investigations referring to the origin of homochirality are reviewed and integrated into the hitherto known state of the art. Attention is directed to an extraterrestrial scenario, which describes the interaction of circularly polarized synchrotron radiation with interstellar organic matter. Following this Bonner‐Rubenstein hypothesis, optically active molecules could be transferred to Earth via comets. We plan to identify any enantiomeric enhancement in organic molecules of the cometary matter in situ. The present preliminary experimental study intends to optimize gas‐chromatographic conditions for the separation of racemates into their enantiomer constituents on the surface of the comet 46P/Wirtanen. Underivatized racemic pairs of alcohols, diols, and phenyl‐substituted amines have been separated with the help of a stationary trifluoroacetyl‐cyclodextrin phase. We are still developing a technique that will enable us to detect any enantiomeric enhancement of specific simple organic molecules both in cometary or Martian matter in situ and in meteorites found on Earth. Chirality 11:575–582, 1999. © 1999 Wiley‐Liss, Inc.     

Molecular biology of Ri-plasmid—A review

Agrobacterium rhizogenes transfers a segment of its plasmid to the plant genome. The transferred DNA contains genes which are involved in the synthesis of plant hormones. These genes express in the plant cell and give rise to rooty-tumors at the infection site. Transgenic plants can be readily regenerated from the rooty-tumors and the transferred DNA is transmitted to progeny plants. High regeneration potential and sustained maintenance of transferred DNA makes the bacterium a suitable vector for plant genetic engineering. DNA sequences homologous to the transferred DNA ofAgrobacterium rhizogenes were detected in some untransformed plant species suggesting a past infection byAgrobacterium rhizogenes during evolution of some genera, notably Nicotiana.     

《Molecular Plant》文章中文摘要

2010年第3卷第3期 题目：缩小目标——迈向成功的耐旱作物基因工程（综述） 摘要：干旱是影响全球农业的最严重的环境胁迫。为保证世界上越来越多的人口的粮食供应，开发潜在产量及在水资源有限的环境下保持作物产量的稳定是必须主动采取的紧急任务。利用模式植物拟南芥通过遗传、分子与生化研究寻找植物抗旱响应关键调控子，已作出了巨大努力。     

Molecular genetics of Parkinson’s disease

The current views on the role of genetic factors in the pathogenesis of Parkinson’s disease are considered. The review is focused on monogenic forms of the disease, for which 11 loci are mapped and seven genes whose mutations cause the disease are identified. In addition, a number of candidate genes for sporadic Parkinson’s disease are described. The further development of studying genetic bases of Parkinson’s disease will follow two main directions: in-depth analysis of genes related to the monogenic form of the disease and more large-scale associative investigation of candidate genes for the sporadic form of Parkinson’s disease.     

《Molecular Plant》文章中文摘要

2011年第4卷第1期（http：//mplant.oxfordjournals.org/content/vol4/issue1/index.dtl）1 Armbruster U,Pesaresi P,Pribil M,Hertle A,Leister D（2011）.Update on chloroplast research：new tools,new topics,and new trends.Mol Plant,4（1）：1-16题目：叶绿体研究前沿——新工具、新主题、新趋势（综述）摘要：叶绿体,质体的绿色分化类型,是光合作用和其他重要植物功能进行的场所。过去十年,遗传学和基因组学的技术极大地促进了叶绿体蛋白的发现和功能研究。实际上,目前通过高通量方法学,特别是蛋白质组学和转录组学,获得的数据通常被用于确定叶绿体蛋白的功能。对叶绿体许多生理过程的认识,特别是与光合作用和光呼吸相关的知识获得了极大的拓展,使得利用生物技术方法改进作物生长成为可能。同时,鉴定叶绿体蛋白的全体互补蛋白并且研究它们相互作用的工作进展迅速,使得这个细胞器成为植物系统生物学研究的重要目标。     

《Molecular Plant》文章中文摘要

1 Kong S-G, Wada M （2011）. New insights into dynamic actin-based chloroplast photorelocation movement. Mol Plant, 4 （5）： 771-781 题目：肌动蛋白介导的叶绿体光再定位运动（综述） 摘要：叶绿体运动是植物在不同光环境下生存的基础。向光色素（植物特异的蓝光活化受体激酶）通过感受光的强度和方向介导反应。近来，研究发现新的叶绿体肌动蛋白（cp—actin）纤丝在定向性的叶绿体光再定位运动中有重要作用。通过分子遗传学和细胞生物学分析，近来在这个领域取得了突出的进展。这篇综述叙述了参与叶绿体运动的因子以及它们对叶绿体肌动蛋白纤丝的调节作用，为进一步研究其生化活性和功能提供了基础。