Open Access Published by De Gruyter

Volume 4 Issue 6

Issue of Biomolecular Concepts

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Contents
Journal Overview

Masthead

Publicly Available November 23, 2013

Masthead

Page range: i-iii

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Reviews

Open Access October 29, 2013

MurD enzymes: some recent developments

Roman Šink, Hélène Barreteau, Delphine Patin, Dominique Mengin-Lecreulx, Stanislav Gobec, Didier Blanot

Page range: 539-556

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Abstract

The synthesis of the peptide stem of bacterial peptidoglycan involves four enzymes, the Mur ligases (MurC, D, E and F). Among them, MurD is responsible for the ATP-dependent addition of d -glutamic acid to UDP-MurNAc- l -Ala, a reaction which involves acyl-phosphate and tetrahedral intermediates. Like most enzymes of peptidoglycan biosynthesis, MurD constitutes an attractive target for the design and synthesis of new antibacterial agents. Escherichia coli MurD has been the first Mur ligase for which the tridimensional (3D) structure was solved. Thereafter, several co-crystal structures with different ligands or inhibitors were released. In the present review, we will deal with work performed on substrate specificity, reaction mechanism and 3D structure of E. coli MurD. Then, a part of the review will be devoted to recent work on MurD orthologs from species other than E. coli and to cellular organization of Mur ligases and in vivo regulation of the MurD activity. Finally, we will review the different classes of MurD inhibitors that have been designed and assayed to date with the hope of obtaining new antibacterial compounds.

Open Access November 23, 2013

Viroid-induced DNA methylation in plants

Athanasios Dalakouras, Elena Dadami, Michael Wassenegger

Page range: 557-565

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Abstract

In eukaryotes, DNA methylation refers to the addition of a methyl group to the fifth atom in the six-atom ring of cytosine residues. At least in plants, DNA regions that become de novo methylated can be defined by homologous RNA molecules in a process termed RNA-directed DNA methylation (RdDM). RdDM was first discovered in viroid-infected plants. Viroids are pathogenic circular, non-coding, single-stranded RNA molecules. Members of the Pospiviroidae family replicate in the nucleus through double-stranded RNA intermediates, attracting the host RNA silencing machinery. The recruitment of this machinery results in the production of viroid-derived small RNAs (vd-sRNAs) that mediate RNA degradation and DNA methylation of cognate sequences. Here, we provide an overview of the cumulative data on the field of viroid-induced RdDM and discuss three possible scenarios concerning the mechanistic details of its establishment.

Publicly Available October 22, 2013

Gene amplification: mechanisms and involvement in cancer

Atsuka Matsui, Tatsuya Ihara, Hiraku Suda, Hirofumi Mikami, Kentaro Semba

Page range: 567-582

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Abstract

Gene amplification was recognized as a physiological process during the development of Drosophila melanogaster . Intriguingly, mammalian cells use this mechanism to overexpress particular genes for survival under stress, such as during exposure to cytotoxic drugs. One well-known example is the amplification of the dihydrofolate reductase gene observed in methotrexate-resistant cells. Four models have been proposed for the generation of amplifications: extrareplication and recombination, the breakage-fusion-bridge cycle, double rolling-circle replication, and replication fork stalling and template switching. Gene amplification is a typical genetic alteration in cancer, and historically many oncogenes have been identified in the amplified regions. In this regard, novel cancer-associated genes may remain to be identified in the amplified regions. Recent comprehensive approaches have further revealed that co-amplified genes also contribute to tumorigenesis in concert with known oncogenes in the same amplicons. Considering that cancer develops through the alteration of multiple genes, gene amplification is an effective acceleration machinery to promote tumorigenesis. Identification of cancer-associated genes could provide novel and effective therapeutic targets.

Open Access November 7, 2013

Small heat shock proteins: recent developments

Benjamin Dennis Eisenhardt

Page range: 583-595

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Abstract

Small heat shock proteins (sHSPs) are abundantly present in many different organisms at elevated temperatures. Members of the subgroup of alpha crystallin domain (ACD)-type sHSPs belong to the large family of protein chaperones. They bind non-native proteins in an ATP-independent manner, thereby holding the incorporated clients soluble for subsequent refolding by other molecular chaperoning systems. sHSPs do not actively refold incorporated peptides therefore they are sometimes referred to as holdases. Varying numbers of sHSPs have been documented in the different domains of life and dependent on the analyzed organism. Generally, diverse sHSPs possess more sequence similarities in the conserved ACD, whereas the N- and C-terminal extensions are less conserved. Despite their designation as sHSPs, they are not solely present during heat stress. sHSPs presumably help to protect cells under various stresses, but they were also found during development, e.g., in embryonic development of higher plants which is associated with ongoing seed desiccation. The functional and physiological relevance of several different sHSPs in one organism remains still unclear, especially in plants where several highly similar sHSPs are present in the same compartment. The wide range of biotic and abiotic stresses that induce the expression of multiple sHSP genes makes it challenging to define the physiological relevance of each of these versatile proteins.

Open Access October 14, 2013

Folding of peptides and proteins: role of disulfide bonds, recent developments

Yuji Hidaka, Shigeru Shimamoto

Page range: 597-604

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Abstract

Disulfide-containing proteins are ideal models for studies of protein folding as the folding intermediates can be observed, trapped, and separated by HPLC during the folding reaction. However, regulating or analyzing the structures of folding intermediates of peptides and proteins continues to be a difficult problem. Recently, the development of several techniques in peptide chemistry and biotechnology has resulted in the availability of some powerful tools for studying protein folding in the context of the structural analysis of native, mutant proteins, and folding intermediates. In this review, recent developments in the field of disulfide-coupled peptide and protein folding are discussed, from the viewpoint of chemical and biotechnological methods, such as analytical methods for the detection of disulfide pairings, chemical methods for disulfide bond formation between the defined Cys residues, and applications of diselenide bonds for the regulation of disulfide-coupled peptide and protein folding.

Short Conceptual Overviews

Open Access October 22, 2013

The role of chromogranins in the secretory pathway

Judith Estevez-Herrera, Marta R. Pardo, Natalia Dominguez, Daniel Pereda, Jose D. Machado, Ricardo Borges

Page range: 605-609

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Abstract

Chromogranins (Cgs) are acidic proteins implicated in several physiological processes, including the biogenesis and sorting of secretory vesicles, the generation of bioactive peptides, and the accumulation of soluble species inside large dense core vesicles (LDCV). Indeed, Cgs are the main protein component of the vesicular matrix in LDCV, and they are involved in the concentration of soluble species like neurotransmitters and calcium. Experiments using electrochemical techniques such amperometry, patch amperometry, and intracellular electrochemistry have clarified the functional roles of Cgs in the accumulation and release of catecholamines. We have focused this review at a single event of exocytosis of chromaffin cells from three mouse strains lacking Cgs. Accordingly, in this brief review, we will focus on the role of Cgs in maintaining the intravesicular environment of secretory vesicles and in exocytosis, bringing together the most recent findings from studies on adrenal chromaffin cells.

Open Access November 23, 2013

Selenomethionine metabolism and its toxicity in yeast

Toshihiko Kitajima, Yasunori Chiba

Page range: 611-616

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Abstract

The importance of selenium for organisms can be explained by its existence as selenocysteine in the catalytic centers of glutathione peroxidase and thioredoxin reductase. Another selenoamino acid, selenomethionine, is the major form of selenium in foods, and organisms that require selenium as a nutrient directly metabolize selenomethionine to a reactive form of selenium or store it in general proteins. Selenium is recognized as an essential nutrient for human and animal health; however, its excessive uptake harms mammals and the cytotoxic mechanism of selenium remains unclear. Recent progress in the development of selenium-enriched yeast and selenomethionine-resistant mutant to produce selenomethionine-containing proteins for X-ray crystallography has provided new insights into the molecular mechanism of selenomethionine toxicity. In this review, we describe the metabolism of seleno-compounds in yeast and discuss the cytotoxicity caused by selenomethionine against yeast from a metabolic viewpoint.

About this journal

BioMolecular Concepts is a peer-reviewed open access journal fostering the integration of different fields of biomolecular research. Researchers from all countries are welcome to publish review articles, short conceptual overviews, and original research articles on topics in molecular and cell biology.

History

Founded in 2010, BioMolecular Concepts intends to fill a gap in the current literature in biological research by providing a conceptual platform favoring the development of novel ideas and cross-discipline scientific views, with a focus on research resulting in paradigm changes. Reviews cover novel and original concepts arising from recent findings in forefront fields of biology, summaries of research within these fields, and conclusive extensions resulting in new, testable hypotheses. Of special interest are aspects that can promote related biomolecular and biomedical fields, and how they can lead to more biological insight or potential medical applications.

From 2010 to 2017, the journal was available in the printed version (ISSN: 1868-5021). Since 2018 Biomolecular Concepts has switched to the online version exclusively.

Aims and Scope

The journal aims to provide expert summaries from prominent researchers, and conclusive extensions of research data leading to new and original, testable hypotheses. Aspects of research that can promote related fields, and lead to novel insight into biological mechanisms or potential medical applications are of special interest. Original research articles reporting new data of broad significance are also welcome.

The journal publishes research results in the following fields:

cellular and molecular biology
genetics and epigenetics
biochemistry
structural biology
neurosciences
developmental biology
molecular medicine
pharmacology
microbiology
plant biology and biotechnology.