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Biochemical Society Transactions

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https://www.readbyqxmd.com/read/30626709/multilayered-control-of-chromosome-replication-in-caulobacter-crescentus
#1
REVIEW
Antonio Frandi, Justine Collier
The environmental Alphaproteobacterium Caulobacter crescentus 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 per cell cycle. Imbalances in chromosomal copy numbers are the most often highly deleterious, if not lethal...
January 9, 2019: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30626708/ghrelin-octanoylation-by-ghrelin-o-acyltransferase-unique-protein-biochemistry-underlying-metabolic-signaling
#2
REVIEW
James L Hougland
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 O -acyltransferase (GOAT), a member of the membrane-bound O -acyltransferase (MBOAT) enzyme family. From the status of ghrelin as the only substrate for GOAT in the human genome to the source and requirement for the octanoyl acyl donor, the ghrelin-GOAT system is defined by multiple unique aspects within both protein biochemistry and endocrinology...
January 9, 2019: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30626707/hereditary-diseases-of-coenzyme-a-thioester-metabolism
#3
REVIEW
Hao Yang, Chen Zhao, Youlin Wang, Shu Pei Wang, Grant A Mitchell
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. These conditions are increasingly detected by newborn screening. There is a renewed interest in CoA metabolism and in developing effective new treatments. Here, we review theories of the pathophysiology in relation to mitochondrial CoA sequestration, toxicity and redistribution (CASTOR)...
January 9, 2019: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30626706/keeping-the-balance-in-nad-metabolism
#4
REVIEW
Øyvind Strømland, Marc Niere, Andrey A Nikiforov, Magali R VanLinden, Ines Heiland, Mathias Ziegler
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...
January 9, 2019: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30626705/breast-tumour-organoids-promising-models-for-the-genomic-and-functional-characterisation-of-breast-cancer
#5
REVIEW
Charlotte Roelofs, Frédéric Hollande, Richard Redvers, Robin L Anderson, Delphine Merino
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...
January 9, 2019: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30626704/the-role-of-metal-ions-in-the-virulence-and-viability-of-bacterial-pathogens
#6
REVIEW
Stephanie L Begg
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. It is therefore unsurprising that components of the immune response target and exploit both the essentiality of metal ions and their potential toxicity toward invading bacteria...
January 9, 2019: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30626703/learning-the-abcs-one-at-a-time-structure-and-mechanism-of-abc-transporters
#7
REVIEW
Robert C Ford, Konstantinos Beis
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. The TMDs dictate what ligands can be recognised, whereas the NBDs are the power engine of the ABC transporter, carrying out ATP binding and hydrolysis...
January 9, 2019: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30626702/history-and-future-of-shotgun-glycomics
#8
REVIEW
David F Smith, Richard D Cummings, Xuezheng Song
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...
January 9, 2019: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30578348/beneficial-effects-of-spermidine-on-cardiovascular-health-and-longevity-suggest-a-cell-type-specific-import-of-polyamines-by-cardiomyocytes
#9
REVIEW
Bengt-Olof Nilsson, Lo Persson
Recent and exciting in vivo 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...
December 21, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30578347/unusual-relatives-of-the-multisubunit-rna-polymerase
#10
REVIEW
David Forrest
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). In-depth bioinformatics has begun to reveal a wealth of unusual proteins distantly related to msRNAP, identified due to their possession of the aspartate triad and DPBB folds...
December 21, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30578346/noise-in-bacterial-gene-expression
#11
REVIEW
Christoph Engl
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. The production of mRNA and proteins therefore occurs in bursts, with alternating episodes of high and low activity during transcription and translation...
December 21, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30578345/the-role-of-lrrk2-in-cell-signalling
#12
REVIEW
Kirsten Harvey, Tiago F Outeiro
Parkinson's disease (PD) is a common late-onset neurodegenerative disorder known primarily for its motor features. Mutations and risk variants in LRRK2 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. This likely results in an overall gain of LRRK2 cell signalling function contributing to PD pathogenesis. This concept supports the development of LRRK2 kinase inhibitors as disease-modifying treatments, at least for a subset of patients...
December 21, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30578344/transporter-oligomerisation-roles-in-structure-and-function
#13
REVIEW
Cristina Cecchetti, Euan Pyle, Bernadette Byrne
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.
December 21, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30578343/assessing-molecular-interactions-with-biophysical-methods-using-the-validation-cross
#14
REVIEW
Alvar D Gossert
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. The aim of such a validation procedure is to exclude as many artifacts as possible to confirm that there is a true molecular interaction that meets the standards for publishing or is worth investing considerable resources for follow-up activities in a drug discovery project...
December 21, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30559275/control-freaks-signals-and-cues-governing-the-regulation-of-virulence-in-attaching-and-effacing-pathogens
#15
REVIEW
Natasha C A Turner, James P R Connolly, Andrew J Roe
Enterohaemorrhagic Escherichia coli (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...
December 17, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30559274/the-molecular-mechanism-of-dhhc-protein-acyltransferases
#16
REVIEW
Mitra S Rana, Chul-Jin Lee, Anirban Banerjee
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. This, in turn, highlights the important roles that S-acylation plays in human physiology and disease...
December 17, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30559273/the-chemistry-of-the-vitamin-b3-metabolome
#17
REVIEW
Mikhail V Makarov, Samuel A J Trammell, Marie E Migaud
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. Since NAD+ seats at the cross-road between cell metabolism and cell signaling, manipulation of NAD+ bioavailability through vitamin B3 supplementation has become a valuable nutritional and therapeutic avenue...
December 17, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30559272/understanding-cellular-glycan-surfaces-in-the-central-nervous-system
#18
REVIEW
Sameera Iqbal, Mina Ghanimi Fard, Arun Everest-Dass, Nicolle H Packer, Lindsay M Parker
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...
December 17, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30559271/learning-rubisco-s-birth-and-subsequent-environmental-adaptation
#19
REVIEW
Hiroki Ashida, Eiichi Mizohata, Akiho Yokota
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 CO2 -fixing enzyme RuBisCO (ribulose 1,5-bisphosphate carboxylase/oxygenase) began to function in primitive methanogenic archaea and has been evolved as a central CO2 -fixing enzyme in response to the large changes in CO2 and O2 concentrations that occurred in the subsequent 4 billion years...
December 17, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30559270/rho-rock-signaling-regulates-tumor-microenvironment-interactions
#20
REVIEW
Mohammad Zahied Johan, Michael S Samuel
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...
December 17, 2018: Biochemical Society Transactions
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