16,442 results match your criteria Biochemical Society Transactions[Journal]


Twenty years of Mediator complex structural studies.

Biochem Soc Trans 2019 Feb 7. Epub 2019 Feb 7.

UMR 8576, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), CNRS, Univ. Lille, F-59000 Lille, France.

Mediator is a large multiprotein complex conserved in all eukaryotes that plays an essential role in transcriptional regulation. Mediator comprises 25 subunits in yeast and 30 subunits in humans that form three main modules and a separable four-subunit kinase module. For nearly 20 years, because of its size and complexity, Mediator has posed a formidable challenge to structural biologists. Read More

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http://dx.doi.org/10.1042/BST20180608DOI Listing
February 2019

The role of chromosome segregation and nuclear organisation in human subfertility.

Biochem Soc Trans 2019 Feb 7. Epub 2019 Feb 7.

School of Biosciences, University of Kent, Canterbury, U.K.

Spermatogenesis is central to successful sexual reproduction, producing large numbers of haploid motile male gametes. Throughout this process, a series of equational and reductional chromosome segregation precedes radical repackaging of the haploid genome. Faithful chromosome segregation is thus crucial, as is an ordered spatio-temporal 'dance' of packing a large amount of chromatin into a very small space. Read More

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http://dx.doi.org/10.1042/BST20180231DOI Listing
February 2019

Towards functional characterization of archaeal genomic dark matter.

Biochem Soc Trans 2019 Feb 1. Epub 2019 Feb 1.

National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD 20894, U.S.A.

A substantial fraction of archaeal genes, from ∼30% to as much as 80%, encode 'hypothetical' proteins or genomic 'dark matter'. Archaeal genomes typically contain a higher fraction of dark matter compared with bacterial genomes, primarily, because isolation and cultivation of most archaea in the laboratory, and accordingly, experimental characterization of archaeal genes, are difficult. In the present study, we present quantitative characteristics of the archaeal genomic dark matter and discuss comparative genomic approaches for functional prediction for 'hypothetical' proteins. Read More

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http://dx.doi.org/10.1042/BST20180560DOI Listing
February 2019

Emerging paradigms for PilZ domain-mediated C-di-GMP signaling.

Biochem Soc Trans 2019 Feb 1. Epub 2019 Feb 1.

School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, S637551 Singapore

PilZ domain-containing proteins constitute a large family of bacterial signaling proteins. As a widely distributed protein domain for the binding of the second messenger c-di-GMP, the canonical PilZ domain contains a set of motifs that define the binding site for c-di-GMP and an allosteric switch for propagating local conformational changes. Here, we summarize some new insights gathered from recent studies on the commonly occurring single-domain PilZ proteins, YcgR-like proteins and PilZ domain-containing cellulose synthases. Read More

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http://dx.doi.org/10.1042/BST20180543DOI Listing
February 2019

The demise of catalysis, but new functions arise: pseudoenzymes as the phoenixes of the protein world.

Biochem Soc Trans 2019 Feb 1. Epub 2019 Feb 1.

Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, U.S.A.

Pseudoenzymes are noncatalytic homologues of enzymes and are found in most enzyme families. Although lacking catalytic activity and sometimes referred to as 'dead' enzymes, they instead resemble phoenixes because the loss of a catalytic function during evolution was associated with the development of vital new functions. They are important in regulating the activity and location of catalytically active homologues, scaffolding the assembly of signaling complexes, and regulating transcription or translation. Read More

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http://dx.doi.org/10.1042/BST20180473DOI Listing
February 2019

ADP-ribosylation and intracellular traffic: an emerging role for PARP enzymes.

Biochem Soc Trans 2019 Feb 1. Epub 2019 Feb 1.

Institute of Protein Biochemistry, National Research Council, Via Pietro Castellino 111, 80131 Naples, Italy

ADP-ribosylation is an ancient and reversible post-translational modification (PTM) of proteins, in which the ADP-ribose moiety is transferred from NAD to target proteins by members of poly-ADP-ribosyl polymerase (PARP) family. The 17 members of this family have been involved in a variety of cellular functions, where their regulatory roles are exerted through the modification of specific substrates, whose identification is crucial to fully define the contribution of this PTM. Evidence of the role of the PARPs is now available both in the context of physiological processes and of cell responses to stress or starvation. Read More

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http://dx.doi.org/10.1042/BST20180416DOI Listing
February 2019

Transcription initiation factor TBP: old friend new questions.

Biochem Soc Trans 2019 Feb 1. Epub 2019 Feb 1.

Institute of Biochemistry, Genetics and Microbiology, University of Regensburg, Universitätsstraße 31, 93053 Regensburg, Germany

In all domains of life, the regulation of transcription by DNA-dependent RNA polymerases (RNAPs) is achieved at the level of initiation to a large extent. Whereas bacterial promoters are recognized by a σ-factor bound to the RNAP, a complex set of transcription factors that recognize specific promoter elements is employed by archaeal and eukaryotic RNAPs. These initiation factors are of particular interest since the regulation of transcription critically relies on initiation rates and thus formation of pre-initiation complexes. Read More

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http://dx.doi.org/10.1042/BST20180623DOI Listing
February 2019

Dissecting metabolism using zebrafish models of disease.

Biochem Soc Trans 2019 Jan 30. Epub 2019 Jan 30.

Peter MacCallum Cancer Centre, 305 Grattan St., Melbourne, Victoria 3000, Australia

Zebrafish () are becoming an increasingly powerful model organism to study the role of metabolism in disease. Since its inception, the zebrafish model has relied on unique attributes such as the transparency of embryos, high fecundity and conservation with higher vertebrates, to perform phenotype-driven chemical and genetic screens. In this review, we describe how zebrafish have been used to reveal novel mechanisms by which metabolism regulates embryonic development, obesity, fatty liver disease and cancer. Read More

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http://dx.doi.org/10.1042/BST20180335DOI Listing
January 2019
1 Read

Detecting ovarian cancer using extracellular vesicles: progress and possibilities.

Biochem Soc Trans 2019 Jan 30. Epub 2019 Jan 30.

Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Gipsy Lane, Headington, Oxford OX3 0BP, U.K.

Ovarian cancer (OC) is the deadliest gynecological malignancy. Most patients are diagnosed when they are already in the later stages of the disease. Earlier detection of OC dramatically improves the overall survival, but this is rarely achieved as there is a lack of clinically implemented biomarkers of early disease. Read More

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http://biochemsoctrans.org/lookup/doi/10.1042/BST20180286
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http://dx.doi.org/10.1042/BST20180286DOI Listing
January 2019
1 Read

Adenine nucleotides as paracrine mediators and intracellular second messengers in immunity and inflammation.

Biochem Soc Trans 2019 Jan 23. Epub 2019 Jan 23.

Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany

Adenine nucleotides (AdNs) play important roles in immunity and inflammation. Extracellular AdNs, such as adenosine triphosphate (ATP) or nicotinamide adenine dinucleotide (NAD) and their metabolites, act as paracrine messengers by fine-tuning both pro- and anti-inflammatory processes. Moreover, intracellular AdNs derived from ATP or NAD play important roles in many cells of the immune system, including T lymphocytes, macrophages, neutrophils and others. Read More

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http://dx.doi.org/10.1042/BST20180419DOI Listing
January 2019

H2 influenza viruses: designing vaccines against future H2 pandemics.

Biochem Soc Trans 2019 Jan 15. Epub 2019 Jan 15.

Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, U.S.A.

Influenza-related pathologies affect millions of people each year and the impact of influenza on the global economy and in our everyday lives has been well documented. Influenza viruses not only infect humans but also are zoonotic pathogens that infect various avian and mammalian species, which serve as viral reservoirs. While there are several strains of influenza currently circulating in animal species, H2 influenza viruses have a unique history and are of particular concern. Read More

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http://biochemsoctrans.org/lookup/doi/10.1042/BST20180602
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http://dx.doi.org/10.1042/BST20180602DOI Listing
January 2019
11 Reads

Initiating DNA replication: a matter of prime importance.

Authors:
Stephen D Bell

Biochem Soc Trans 2019 Jan 15. Epub 2019 Jan 15.

Department of Molecular and Cellular Biochemistry, Indiana University, Simon Hall MSB, 212 S Hawthorne Dr., Bloomington, IN 47405, U.S.A.

It has been known for decades that the principal replicative DNA polymerases that effect genome replication are incapable of starting DNA synthesis Rather, they require a 3'-OH group from which to extend a DNA chain. Cellular DNA replication systems exploit a dedicated, limited processivity RNA polymerase, termed primase, that synthesizes a short oligoribonucleotide primer which is then extended by a DNA polymerase. Thus, primases can initiate synthesis, proceed with primer elongation for a short distance then transfer the primer to a DNA polymerase. Read More

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http://dx.doi.org/10.1042/BST20180627DOI Listing
January 2019
1 Read

An updated structural classification of replicative DNA polymerases.

Biochem Soc Trans 2019 Jan 15. Epub 2019 Jan 15.

Unit of Structural Dynamics of Macromolecules, CNRS UMR 3528, Pasteur Institute, 75015 Paris, France

Replicative DNA polymerases are nano-machines essential to life, which have evolved the ability to copy the genome with high fidelity and high processivity. In contrast with cellular transcriptases and ribosome machines, which evolved by accretion of complexity from a conserved catalytic core, no replicative DNA polymerase is universally conserved. Strikingly, four different families of DNA polymerases have evolved to perform DNA replication in the three domains of life. Read More

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http://dx.doi.org/10.1042/BST20180579DOI Listing
January 2019
1 Read

Mechanisms of antibiotics inhibiting bacterial RNA polymerase.

Biochem Soc Trans 2019 Jan 15. Epub 2019 Jan 15.

Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle Upon Tyne NE2 4AX, U.K.

Transcription, the first phase of gene expression, is performed by the multi-subunit RNA polymerase (RNAP). Bacterial RNAP is a validated target for clinical antibiotics. Many natural and synthetic compounds are now known to target RNAP, inhibiting various stages of the transcription cycle. Read More

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http://dx.doi.org/10.1042/BST20180499DOI Listing
January 2019
1 Read

Structural mass spectrometry comes of age: new insight into protein structure, function and interactions.

Biochem Soc Trans 2019 Jan 15. Epub 2019 Jan 15.

Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, Montpellier, France

Mass spectrometry (MS) provides an impressive array of information about the structure, function and interactions of proteins. In recent years, many new developments have been in the field of native MS and these exemplify a new coming of age of this field. In this mini review, we connect the latest methodological and instrumental developments in native MS to the new insights these have enabled. Read More

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http://dx.doi.org/10.1042/BST20180356DOI Listing
January 2019
1 Read

Cryo-EM in drug discovery.

Biochem Soc Trans 2019 Jan 15. Epub 2019 Jan 15.

Astex Pharmaceuticals, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, U.K.

The impact of structural biology on drug discovery is well documented, and the workhorse technique for the past 30 years or so has been X-ray crystallography. With the advent of several technological improvements, including direct electron detectors, automation, better microscope vacuums and lenses, phase plates and improvements in computing power enabled by GPUs, it is now possible to record and analyse images of protein structures containing high-resolution information. This review, from a pharmaceutical perspective, highlights some of the most relevant and interesting protein structures for the pharmaceutical industry and shows examples of how ligand-binding sites, membrane proteins, both big and small, pseudo symmetry and complexes are being addressed by this technique. Read More

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http://dx.doi.org/10.1042/BST20180267DOI Listing
January 2019
1 Read

Structure and mechanism of the ESCRT pathway AAA+ ATPase Vps4.

Biochem Soc Trans 2019 Jan 15. Epub 2019 Jan 15.

Department of Biochemistry, University of Utah, Salt Lake City, UT 84112-5650, U.S.A.

The progression of ESCRT (Endosomal Sorting Complexes Required for Transport) pathways, which mediate numerous cellular membrane fission events, is driven by the enzyme Vps4. Understanding of Vps4 mechanism is, therefore, of fundamental importance in its own right and, moreover, it is highly relevant to the understanding of many related AAA+ ATPases that function in multiple facets of cell biology. Vps4 unfolds its ESCRT-III protein substrates by translocating them through its central hexameric pore, thereby driving membrane fission and recycling of ESCRT-III subunits. Read More

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http://dx.doi.org/10.1042/BST20180260DOI Listing
January 2019
1 Read

The role of extracellular vesicles in cancer microenvironment and metastasis: myths and challenges.

Biochem Soc Trans 2019 Jan 15. Epub 2019 Jan 15.

Department of Urology, Mayo Clinic, Rochester, MN, U.S.A.

The concept of vesicles or cell debris released by cancer cells to promote metastasis is not new, but the mechanisms used to currently ascribe their impact in metastasis are of intense debate. A significant increase in reports describing the role of cancer-derived EVs in cancer metastasis has been followed by a growing amount of uncertainty behind these claims. This review will delve into the role of EVs in promoting cancer metastasis by relying on a balanced perspective that looks at challenges faced previously by extracellular vesicle biologists, current technical limitations in the field, and overlooked physiologic mechanisms that may play a confounding role. Read More

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http://dx.doi.org/10.1042/BST20180253DOI Listing
January 2019
1 Read

Multilayered control of chromosome replication in .

Biochem Soc Trans 2019 Jan 9. Epub 2019 Jan 9.

Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Quartier UNIL/Sorge, Lausanne CH 1015, Switzerland

The environmental is a classical model to study the regulation of the bacterial cell cycle. It divides asymmetrically, giving a stalked cell that immediately enters S phase and a swarmer cell that stays in the G1 phase until it differentiates into a stalked cell. Its genome consists in a single circular chromosome whose replication is tightly regulated so that it happens only in stalked cells and only once cell cycle. Read More

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http://dx.doi.org/10.1042/BST20180460DOI Listing
January 2019
1 Read

Ghrelin octanoylation by ghrelin -acyltransferase: Unique protein biochemistry underlying metabolic signaling.

Authors:
James L Hougland

Biochem Soc Trans 2019 Jan 9. Epub 2019 Jan 9.

Department of Chemistry, Syracuse University, Syracuse, NY, U.S.A.

Ghrelin is a small peptide hormone that requires a unique post-translational modification, serine octanoylation, to bind and activate the GHS-R1a receptor. Ghrelin signaling is implicated in a variety of neurological and physiological processes, but is most well known for its roles in controlling hunger and metabolic regulation. Ghrelin octanoylation is catalyzed by ghrelin -acyltransferase (GOAT), a member of the membrane-bound -acyltransferase (MBOAT) enzyme family. Read More

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http://dx.doi.org/10.1042/BST20180436DOI Listing
January 2019
2 Reads

Hereditary diseases of coenzyme A thioester metabolism.

Biochem Soc Trans 2019 Jan 9. Epub 2019 Jan 9.

Division of Medical Genetics, Department of Pediatrics, CHU Sainte-Justine and Université de Montréal, Montréal, QC, Canada

Coenzyme A (CoA) thioesters (acyl-CoAs) are essential intermediates of metabolism. Inborn errors of acyl-CoA metabolism include a large fraction of the classical organic acidemias. These conditions can involve liver, muscle, heart and brain, and can be fatal. Read More

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http://dx.doi.org/10.1042/BST20180423DOI Listing
January 2019
1 Read

Keeping the balance in NAD metabolism.

Biochem Soc Trans 2019 Jan 9. Epub 2019 Jan 9.

Department of Biomedicine, University of Bergen, 5009 Bergen, Norway

Research over the last few decades has extended our understanding of nicotinamide adenine dinucleotide (NAD) from a vital redox carrier to an important signalling molecule that is involved in the regulation of a multitude of fundamental cellular processes. This includes DNA repair, cell cycle regulation, gene expression and calcium signalling, in which NAD is a substrate for several families of regulatory proteins, such as sirtuins and ADP-ribosyltransferases. At the molecular level, NAD-dependent signalling events differ from hydride transfer by cleavage of the dinucleotide into an ADP-ribosyl moiety and nicotinamide. Read More

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http://dx.doi.org/10.1042/BST20180417DOI Listing
January 2019
2 Reads

Breast tumour organoids: promising models for the genomic and functional characterisation of breast cancer.

Biochem Soc Trans 2019 Jan 9. Epub 2019 Jan 9.

Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria 3084, Australia

Until recently, established cancer cell lines have been used extensively in breast cancer research, due largely to the difficulties associated with the manipulation and long-term maintenance in culture of primary tumour cells from patients. The recent development of organoid cultures has provided new opportunities to model and analyse patient samples, allowing the propagation of malignant cells under conditions that resemble the three-dimensional growth of breast tumours. They have proved efficacious in preserving the heterogeneity of primary samples and are emerging as a new model to further characterise the molecular features of breast cancer. Read More

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http://dx.doi.org/10.1042/BST20180375DOI Listing
January 2019
1 Read

The role of metal ions in the virulence and viability of bacterial pathogens.

Authors:
Stephanie L Begg

Biochem Soc Trans 2019 Jan 9. Epub 2019 Jan 9.

Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia

Metal ions fulfil a plethora of essential roles within bacterial pathogens. In addition to acting as necessary cofactors for cellular proteins, making them indispensable for both protein structure and function, they also fulfil roles in signalling and regulation of virulence. Consequently, the maintenance of cellular metal ion homeostasis is crucial for bacterial viability and pathogenicity. Read More

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http://biochemsoctrans.org/lookup/doi/10.1042/BST20180275
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http://dx.doi.org/10.1042/BST20180275DOI Listing
January 2019
9 Reads

Learning the ABCs one at a time: structure and mechanism of ABC transporters.

Biochem Soc Trans 2019 Jan 9. Epub 2019 Jan 9.

Department of Life Sciences, Imperial College London, Exhibition Road, London, South Kensington SW7 2AZ, U.K.

ATP-binding cassette (ABC) transporters are essential proteins that are found across all kingdoms of life. ABC transporters harness the energy of ATP hydrolysis to drive the import of nutrients inside bacterial cells or the export of toxic compounds or essential lipids across bacteria and eukaryotic membranes. Typically, ABC transporters consist of transmembrane domains (TMDs) and nucleotide-binding domains (NBDs) to bind their substrate and ATP, respectively. Read More

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http://dx.doi.org/10.1042/BST20180147DOI Listing
January 2019
1 Read

History and future of shotgun glycomics.

Biochem Soc Trans 2019 Jan 9. Epub 2019 Jan 9.

Emory Comprehensive Glycomics Center, Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, U.S.A.

Glycans in polysaccharides and glycoconjugates of the hydrophilic exterior of all animal cells participate in signal transduction, cellular adhesion, intercellular signaling, and sites for binding of pathogens largely through protein-glycan interactions. Microarrays of defined glycans have been used to study the binding specificities of biologically relevant glycan-binding proteins (GBP), but such arrays are limited by their lack of diversity or relevance to the GBP being investigated. Shotgun glycan microarrays are made up of structurally undefined glycans that were released from natural sources, labeled with bifunctional reagents so that they can be monitored during their purification using multidimensional chromatographic procedures, stored as a tagged glycan library (TGL) and subsequently printed onto microarrays at equal molar concentrations. Read More

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http://dx.doi.org/10.1042/BST20170487DOI Listing
January 2019
1 Read

Beneficial effects of spermidine on cardiovascular health and longevity suggest a cell type-specific import of polyamines by cardiomyocytes.

Biochem Soc Trans 2018 Dec 21. Epub 2018 Dec 21.

Department of Experimental Medical Science, Lund University, BMC D12, SE-22184 Lund, Sweden.

Recent and exciting studies show that supplementation with the polyamine spermidine (Spd) is cardioprotective and prolongs lifespan in both mice and humans. The mechanisms behind Spd-induced cardioprotection are supposed to involve Spd-evoked stimulation of autophagy, mitophagy and mitochondrial respiration and improved the mechano-elastical function of cardiomyocytes. Although cellular uptake of Spd was not characterized, these results suggest that Spd is imported by the cardiomyocytes and acts intracellularly. Read More

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http://biochemsoctrans.org/lookup/doi/10.1042/BST20180622
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http://dx.doi.org/10.1042/BST20180622DOI Listing
December 2018
2 Reads

Unusual relatives of the multisubunit RNA polymerase.

Authors:
David Forrest

Biochem Soc Trans 2018 Dec 21. Epub 2018 Dec 21.

Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Baddiley-Clark Building, Richardson Road, Newcastle upon Tyne NE2 4AX, U.K.

Transcription, the first step of gene expression, is accomplished in all domains of life by the multisubunit RNA polymerase (msRNAP). Accordingly, the msRNAP is an ancient enzyme that is ubiquitous across all cellular organisms. Conserved in absolutely all msRNAPs is the catalytic magnesium-binding aspartate triad and the structural fold it is present on, the double ψ β barrel (DPBB). Read More

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http://biochemsoctrans.org/lookup/doi/10.1042/BST20180505
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http://dx.doi.org/10.1042/BST20180505DOI Listing
December 2018
3 Reads

Noise in bacterial gene expression.

Authors:
Christoph Engl

Biochem Soc Trans 2018 Dec 21. Epub 2018 Dec 21.

School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, U.K.

The expression level of a gene can fluctuate significantly between individuals within a population of genetically identical cells. The resultant phenotypic heterogeneity could be exploited by bacteria to adapt to changing environmental conditions. Noise is hence a genome-wide phenomenon that arises from the stochastic nature of the biochemical reactions that take place during gene expression and the relatively low abundance of the molecules involved. Read More

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http://dx.doi.org/10.1042/BST20180500DOI Listing
December 2018
1 Read

The role of LRRK2 in cell signalling.

Biochem Soc Trans 2018 Dec 21. Epub 2018 Dec 21.

Department of Experimental Neurodegeneration, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany.

Parkinson's disease (PD) is a common late-onset neurodegenerative disorder known primarily for its motor features. Mutations and risk variants in cause familial and idiopathic forms of PD. Mutations segregating with disease are found in the LRRK2 GTPase and kinase domains, affecting catalytic activity and protein-protein interactions. Read More

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http://biochemsoctrans.org/lookup/doi/10.1042/BST20180464
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http://dx.doi.org/10.1042/BST20180464DOI Listing
December 2018
6 Reads

Transporter oligomerisation: roles in structure and function.

Biochem Soc Trans 2018 Dec 21. Epub 2018 Dec 21.

Department of Life Sciences, Imperial College London, London SW7 2AZ, U.K.

Oligomerisation is a key feature of integral membrane transporters with roles in structure, function and stability. In this review, we cover some very recent advances in our understanding of how oligomerisation affects these key transporter features, with emphasis on a few groups of transporters, including the nucleobase ascorbate transporters, neurotransmitter sodium symporters and major facilitator superfamily members. Read More

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http://biochemsoctrans.org/lookup/doi/10.1042/BST20180316
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http://dx.doi.org/10.1042/BST20180316DOI Listing
December 2018
5 Reads

Assessing molecular interactions with biophysical methods using the validation cross.

Authors:
Alvar D Gossert

Biochem Soc Trans 2018 Dec 21. Epub 2018 Dec 21.

Institute of Molecular Biology and Biophysics, ETH Zürich, 8093 Zürich, Switzerland

There are numerous methods for studying molecular interactions. However, each method gives rise to false negative- or false positive binding results, stemming from artifacts of the scientific equipment or from shortcomings of the experimental format. To validate an initial positive binding result, additional methods need to be applied to cover the shortcomings of the primary experiment. Read More

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http://biochemsoctrans.org/lookup/doi/10.1042/BST20180271
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http://dx.doi.org/10.1042/BST20180271DOI Listing
December 2018
2 Reads

Control freaks-signals and cues governing the regulation of virulence in attaching and effacing pathogens.

Biochem Soc Trans 2018 Dec 17. Epub 2018 Dec 17.

Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, U.K.

Enterohaemorrhagic (EHEC) mediates disease using a type 3 secretion system (T3SS), which is encoded on the locus of enterocyte effacement (LEE) and is tightly controlled by master regulators. This system is further modulated by a number of signals that help to fine-tune virulence, including metabolic, environmental and chemical signals. Since the LEE and its master regulator, Ler, were established, there have been numerous scientific advancements in understanding the regulation and expression of virulence factors in EHEC. Read More

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http://dx.doi.org/10.1042/BST20180546DOI Listing
December 2018
2 Reads

The molecular mechanism of DHHC protein acyltransferases.

Biochem Soc Trans 2018 Dec 17. Epub 2018 Dec 17.

Cell Biology and Neurobiology Branch, National Institutes of Child Health and Human, Development, National Institutes of Health, Bethesda, MD 20892, U.S.A.

Protein S-acylation is a reversible lipidic posttranslational modification where a fatty acid chain is covalently linked to cysteine residues by a thioester linkage. A family of integral membrane enzymes known as DHHC protein acyltransferases (DHHC-PATs) catalyze this reaction. With the rapid development of the techniques used for identifying lipidated proteins, the repertoire of S-acylated proteins continues to increase. Read More

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http://dx.doi.org/10.1042/BST20180429DOI Listing
December 2018
1 Read

The chemistry of the vitamin B3 metabolome.

Biochem Soc Trans 2018 Dec 17. Epub 2018 Dec 17.

Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Ave, Mobile 36604, AL, U.S.A.

The functional cofactors derived from vitamin B3 are nicotinamide adenine dinucleotide (NAD), its phosphorylated form, nicotinamide adenine dinucleotide phosphate (NADP) and their reduced forms (NAD(P)H). These cofactors, together referred as the NAD(P)(H) pool, are intimately implicated in all essential bioenergetics, anabolic and catabolic pathways in all forms of life. This pool also contributes to post-translational protein modifications and second messenger generation. Read More

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http://dx.doi.org/10.1042/BST20180420DOI Listing
December 2018
1 Read

Understanding cellular glycan surfaces in the central nervous system.

Biochem Soc Trans 2018 Dec 17. Epub 2018 Dec 17.

Department of Molecular Sciences, ARC Centre of Excellence for Nanoscale BioPhotonics, Macquarie University, Sydney, NSW 2109, Australia

Glycosylation, the enzymatic process by which glycans are attached to proteins and lipids, is the most abundant and functionally important type of post-translational modification associated with brain development, neurodegenerative disorders, psychopathologies and brain cancers. Glycan structures are diverse and complex; however, they have been detected and targeted in the central nervous system (CNS) by various immunohistochemical detection methods using glycan-binding proteins such as anti-glycan antibodies or lectins and/or characterized with analytical techniques such as chromatography and mass spectrometry. The glycan structures on glycoproteins and glycolipids expressed in neural stem cells play key roles in neural development, biological processes and CNS maintenance, such as cell adhesion, signal transduction, molecular trafficking and differentiation. Read More

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http://dx.doi.org/10.1042/BST20180330DOI Listing
December 2018
2 Reads

Learning RuBisCO's birth and subsequent environmental adaptation.

Biochem Soc Trans 2018 Dec 17. Epub 2018 Dec 17.

Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan

It is believed that organisms that first appeared after the formation of the earth lived in a very limited environment, making full use of the limited number of genes. From these early organisms' genes, more were created by replication, mutation, recombination, translocation, and transmission of other organisms' DNA; thus, it became possible for ancient organisms to grow in various environments. The photosynthetic CO-fixing enzyme RuBisCO (ribulose 1,5-bisphosphate carboxylase/oxygenase) began to function in primitive methanogenic archaea and has been evolved as a central CO-fixing enzyme in response to the large changes in CO and O concentrations that occurred in the subsequent 4 billion years. Read More

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http://dx.doi.org/10.1042/BST20180449DOI Listing
December 2018
1 Read

Rho-ROCK signaling regulates tumor-microenvironment interactions.

Biochem Soc Trans 2018 Dec 17. Epub 2018 Dec 17.

Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, South Australia, Australia

Reciprocal biochemical and biophysical interactions between tumor cells, stromal cells and the extracellular matrix (ECM) result in a unique tumor microenvironment that determines disease outcome. The cellular component of the tumor microenvironment contributes to tumor growth by providing nutrients, assisting in the infiltration of immune cells and regulating the production and remodeling of the ECM. The ECM is a noncellular component of the tumor microenvironment and provides both physical and biochemical support to the tumor cells. Read More

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http://dx.doi.org/10.1042/BST20180334DOI Listing
December 2018
1 Read

Structural biology and structure-function relationships of membrane proteins.

Biochem Soc Trans 2018 Dec 17. Epub 2018 Dec 17.

National Physical Laboratory, Hampton Road, Teddington TW11 0LW, U.K.

The study of structure-function relationships of membrane proteins (MPs) has been one of the major goals in the field of structural biology. Many Noble Prizes regarding remarkable accomplishments in MP structure determination and biochemistry have been awarded over the last few decades. Mutations or improper folding of these proteins are associated with numerous serious illnesses. Read More

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http://dx.doi.org/10.1042/BST20180269DOI Listing
December 2018
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Small GTPase peripheral binding to membranes: molecular determinants and supramolecular organization.

Biochem Soc Trans 2018 Dec 17. Epub 2018 Dec 17.

CNRS and Ecole Normale Supérieure Paris-Saclay, Cachan, France

Small GTPases regulate many aspects of cell logistics by alternating between an inactive, GDP-bound form and an active, GTP-bound form. This nucleotide switch is coupled to a cytosol/membrane cycle, such that GTP-bound small GTPases carry out their functions at the periphery of endomembranes. A global understanding of the molecular determinants of the interaction of small GTPases with membranes and of the resulting supramolecular organization is beginning to emerge from studies of model systems. Read More

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http://dx.doi.org/10.1042/BST20170525DOI Listing
December 2018
19 Reads

Structure, activation and dysregulation of fibroblast growth factor receptor kinases: perspectives for clinical targeting.

Biochem Soc Trans 2018 12 13;46(6):1753-1770. Epub 2018 Dec 13.

Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.

The receptor tyrosine kinase family of fibroblast growth factor receptors (FGFRs) play crucial roles in embryonic development, metabolism, tissue homeostasis and wound repair via stimulation of intracellular signalling cascades. As a consequence of FGFRs' influence on cell growth, proliferation and differentiation, FGFR signalling is frequently dysregulated in a host of human cancers, variously by means of overexpression, somatic point mutations and gene fusion events. Dysregulation of FGFRs is also the underlying cause of many developmental dysplasias such as hypochondroplasia and achondroplasia. Read More

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http://dx.doi.org/10.1042/BST20180004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299260PMC
December 2018
2 Reads

Correction: Fine details in complex environments: the power of cryo-electron tomography.

Biochem Soc Trans 2018 12 4;46(6):1771. Epub 2018 Dec 4.

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http://dx.doi.org/10.1042/BST20170351_CORDOI Listing
December 2018
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New insights into the adaptive transcriptional response to nitrogen starvation in .

Biochem Soc Trans 2018 12 4;46(6):1721-1728. Epub 2018 Dec 4.

MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, U.K.

Bacterial adaptive responses to biotic and abiotic stresses often involve large-scale reprogramming of the transcriptome. Since nitrogen is an essential component of the bacterial cell, the transcriptional basis of the adaptive response to nitrogen starvation has been well studied. The adaptive response to N starvation in is primarily a 'scavenging response', which results in the transcription of genes required for the transport and catabolism of nitrogenous compounds. Read More

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http://biochemsoctrans.org/lookup/doi/10.1042/BST20180502
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http://dx.doi.org/10.1042/BST20180502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299236PMC
December 2018
5 Reads

PseudoGTPase domains in p190RhoGAP proteins: a mini-review.

Biochem Soc Trans 2018 12 4;46(6):1713-1720. Epub 2018 Dec 4.

Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, U.S.A.

Pseudoenzymes generally lack detectable catalytic activity despite adopting the overall protein fold of their catalytically competent counterparts, indeed 'pseudo' family members seem to be incorporated in all enzyme classes. The small GTPase enzymes are important signaling proteins, and recent studies have identified many new family members with noncanonical residues within the catalytic cleft, termed pseudoGTPases. To illustrate recent discoveries in the field, we use the p190RhoGAP proteins as an example. Read More

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http://biochemsoctrans.org/lookup/doi/10.1042/BST20180481
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http://dx.doi.org/10.1042/BST20180481DOI Listing
December 2018
8 Reads

Functional and behavioral consequences of Parkinson's disease-associated G2019S mutation.

Biochem Soc Trans 2018 12 4;46(6):1697-1705. Epub 2018 Dec 4.

Department of Neuroscience, Friedman Brain Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029, U.S.A.

mutation is the most common inherited, autosomal dominant cause of Parkinson's disease (PD) and has also been observed in sporadic cases. Most mutations result in increased LRRK2 kinase activity. LRRK2 is highly expressed in brain regions that receive dense, convergent innervation by dopaminergic and glutamatergic axons, and its levels rise developmentally coincident with glutamatergic synapse formation. Read More

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http://dx.doi.org/10.1042/BST20180468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311993PMC
December 2018
6 Reads

The precise molecular signals that control endothelial cell-cell adhesion within the vessel wall.

Biochem Soc Trans 2018 12 4;46(6):1673-1680. Epub 2018 Dec 4.

Institute for Molecular Bioscience, Genomics of Development and Disease Division, The University of Queensland, 306 Carmody Road, St Lucia, QLD 4072, Australia

Endothelial cell-cell adhesion within the wall of the vasculature controls a range of physiological processes, such as growth, integrity and barrier function. The adhesive properties of endothelial cells are tightly controlled by a complex cascade of signals transmitted from the surrounding environment or from within the cells themselves, with the dynamic nature of cellular adhesion and the regulating signalling networks now beginning to be appreciated. Here, we summarise the current knowledge of the mechanisms controlling endothelial cell-cell adhesion in the developing and mature blood vasculature. Read More

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http://dx.doi.org/10.1042/BST20180377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299237PMC
December 2018
1 Read

A tough row to hoe: when replication forks encounter DNA damage.

Biochem Soc Trans 2018 12 4;46(6):1643-1651. Epub 2018 Dec 4.

Department of Biomedical Sciences, Cornell University, T2-006C Veterinary Research Tower, Ithaca, NY 14853, U.S.A.

Eukaryotic cells continuously experience DNA damage that can perturb key molecular processes like DNA replication. DNA replication forks that encounter DNA lesions typically slow and may stall, which can lead to highly detrimental fork collapse if appropriate protective measures are not executed. Stabilization and protection of stalled replication forks ensures the possibility of effective fork restart and prevents genomic instability. Read More

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http://dx.doi.org/10.1042/BST20180308DOI Listing
December 2018
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Characterisation of sensor kinase by CD spectroscopy: golden rules and tips.

Biochem Soc Trans 2018 12 4;46(6):1627-1642. Epub 2018 Dec 4.

Diamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, Oxfordshire, U.K.

This is a review that describes the golden rules and tips on how to characterise the molecular interactions of membrane sensor kinase proteins with ligands using mainly circular dichroism (CD) spectroscopy. CD spectroscopy is essential for this task as any conformational change observed in the far-UV (secondary structures (α-helix, β-strands, poly-proline of type II, β-turns, irregular and folding) and near-UV regions [local environment of the aromatic side-chains of amino acid residues (Phe, Tyr and Trp) and ligands (drugs) and prosthetic groups (porphyrins, cofactors and coenzymes (FMN, FAD, NAD))] upon ligand addition to the protein can be used to determine qualitatively and quantitatively ligand-binding interactions. Advantages of using CD versus other techniques will be discussed. Read More

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http://biochemsoctrans.org/lookup/doi/10.1042/BST20180222
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http://dx.doi.org/10.1042/BST20180222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299240PMC
December 2018
8 Reads

Phage-based biocontrol strategies and their application in agriculture and aquaculture.

Biochem Soc Trans 2018 12 4;46(6):1605-1613. Epub 2018 Dec 4.

Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin 9054, New Zealand

Meeting global food demands for a growing human population with finite natural resources is a major challenge. Aquaculture and agriculture are critical to satisfy food requirements, yet suffer significant losses from bacterial diseases. Therefore, there is an urgent need to develop novel antimicrobial strategies, which is heightened by increasing antibiotic resistance. Read More

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http://biochemsoctrans.org/lookup/doi/10.1042/BST20180178
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http://dx.doi.org/10.1042/BST20180178DOI Listing
December 2018
14 Reads

Substrate polyspecificity and conformational relevance in ABC transporters: new insights from structural studies.

Biochem Soc Trans 2018 12 4;46(6):1475-1484. Epub 2018 Dec 4.

Astbury Centre for Structural Molecular Biology, School of Biomedical Science, University of Leeds, Leeds LS2 9JT, U.K.

Transport of molecules and ions across biological membranes is an essential process in all organisms. It is carried out by a range of evolutionarily conserved primary and secondary transporters. A significant portion of the primary transporters belong to the ATP-binding cassette (ABC) superfamily, which utilise the free-energy from ATP hydrolysis to shuttle many different substrates across various biological membranes, and consequently, are involved in both normal and abnormal physiology. Read More

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http://dx.doi.org/10.1042/BST20180146DOI Listing
December 2018
1 Read