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Biochemical Society Transactions

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https://www.readbyqxmd.com/read/30381341/recent-insights-into-lytic-polysaccharide-monooxygenases-lpmos
#1
REVIEW
Tobias Tandrup, Kristian E H Frandsen, Katja S Johansen, Jean-Guy Berrin, Leila Lo Leggio
Lytic polysaccharide monooxygenases (LPMOs) are copper enzymes discovered within the last 10 years. By degrading recalcitrant substrates oxidatively, these enzymes are major contributors to the recycling of carbon in nature and are being used in the biorefinery industry. Recently, two new families of LPMOs have been defined and structurally characterized, AA14 and AA15, sharing many of previously found structural features. However, unlike most LPMOs to date, AA14 degrades xylan in the context of complex substrates, while AA15 is particularly interesting because they expand the presence of LPMOs from the predominantly microbial to the animal kingdom...
October 31, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30381340/specificity-and-selectivity-in-post-translational-biotin-addition
#2
REVIEW
Dorothy Beckett
Biotin, which serves as a carboxyl group carrier in reactions catalyzed by biotin-dependent carboxylases, is essential for life in most organisms. To function in carboxylate transfer, the vitamin must be post-translationally linked to a specific lysine residue on the biotin carboxyl carrier (BCC) of a carboxylase in a reaction catalyzed by biotin protein ligases. Although biotin addition is highly selective for any single carboxylase substrate, observations of interspecies biotinylation suggested little discrimination among the BCCs derived from the carboxylases of a broad range of organisms...
October 31, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30381339/metallocluster-transactions-dynamic-protein-interactions-guide-the-biosynthesis-of-fe-s-clusters-in-bacteria
#3
REVIEW
Chenkang Zheng, Patricia C Dos Santos
Iron-sulfur (Fe-S) clusters are ubiquitous cofactors present in all domains of life. The chemistries catalyzed by these inorganic cofactors are diverse and their associated enzymes are involved in many cellular processes. Despite the wide range of structures reported for Fe-S clusters inserted into proteins, the biological synthesis of all Fe-S clusters starts with the assembly of simple units of 2Fe-2S and 4Fe-4S clusters. Several systems have been associated with the formation of Fe-S clusters in bacteria with varying phylogenetic origins and number of biosynthetic and regulatory components...
October 31, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30381338/comparisons-of-voltage-gated-sodium-channel-structures-with-open-and-closed-gates-and-implications-for-state-dependent-drug-design
#4
REVIEW
Giulia Montini, Jennifer Booker, Altin Sula, B A Wallace
Voltage-gated sodium channels (Navs) are responsible for the initiation of the action potential in excitable cells. Several prokaryotic sodium channels, most notably NavMs from Magnetococcus marinus and NavAb from Arcobacter butzleri , have been shown to be good models for human sodium channels based on their sequence homologies and high levels of functional similarities, including ion flux, and functional consequences of critical mutations. The complete full-length crystal structures of these prokaryotic sodium channels captured in different functional states have now revealed the molecular natures of changes associated with the gating process...
October 31, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30381337/endosomal-trafficking-of-yeast-membrane-proteins
#5
REVIEW
Kamilla M E Laidlaw, Chris MacDonald
Various membrane trafficking pathways transport molecules through the endosomal system of eukaryotic cells, where trafficking decisions control the localisation and activity of a diverse repertoire of membrane protein cargoes. The budding yeast Saccharomyces cerevisiae has been used to discover and define many mechanisms that regulate conserved features of endosomal trafficking. Internalised surface membrane proteins first localise to endosomes before sorting to other compartments. Ubiquitination of endosomal membrane proteins is a signal for their degradation...
October 31, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30381336/next-generation-flexible-formats-of-vnar-domains-expand-the-drug-platform-s-utility-and-developability
#6
REVIEW
Obinna C Ubah, Magdalena J Buschhaus, Laura Ferguson, Marina Kovaleva, John Steven, Andrew J Porter, Caroline J Barelle
Therapeutic mAbs have delivered several blockbuster drugs in oncology and autoimmune inflammatory disease. Revenue for mAbs continues to rise, even in the face of competition from a growing portfolio of biosimilars. Despite this success, there are still limitations associated with the use of mAbs as therapeutic molecules. With a molecular mass of 150 kDa, a two-chain structure and complex glycosylation these challenges include a high cost of goods, limited delivery options, and poor solid tumour penetration...
October 31, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30381335/membrane-protein-engineering-to-the-rescue
#7
REVIEW
Andrea E Rawlings
The inherent hydrophobicity of membrane proteins is a major barrier to membrane protein research and understanding. Their low stability and solubility in aqueous environments coupled with poor expression levels make them a challenging area of research. For many years, the only way of working with membrane proteins was to optimise the environment to suit the protein, through the use of different detergents, solubilising additives, and other adaptations. However, with innovative protein engineering methodologies, the membrane proteins themselves are now being adapted to suit the environment...
October 31, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30381334/structural-snapshots-of-raf-kinase-interactions
#8
REVIEW
Soheila Rezaei Adariani, Marcel Buchholzer, Mohammad Akbarzadeh, Saeideh Nakhaei-Rad, Radovan Dvorsky, Mohammad Reza Ahmadian
RAF (rapidly accelerated fibrosarcoma) Ser/Thr kinases (ARAF, BRAF, and CRAF) link the RAS (rat sarcoma) protein family with the MAPK (mitogen-activated protein kinase) pathway and control cell growth, differentiation, development, aging, and tumorigenesis. Their activity is specifically modulated by protein-protein interactions, post-translational modifications, and conformational changes in specific spatiotemporal patterns via various upstream regulators, including the kinases, phosphatase, GTPases, and scaffold and modulator proteins...
October 31, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30381333/therapeutic-strategies-to-target-microbial-protein-glycosaminoglycan-interactions
#9
REVIEW
Johannes Almer, Bernd Gesslbauer, Andreas J Kungl
Glycans are involved in a plethora of human pathologies including infectious diseases. Especially, glycosaminoglycans (GAGs), like heparan sulfate and chondroitin sulfate, have been found to be involved in different crucial stages of microbial invasion. Here, we review various therapeutic approaches, which target the interface of host GAGs and microbial proteins and discuss their limitations and challenges for drug development.
October 31, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30242121/cell-cycle-dependent-phosphorylation-and-regulation-of-cellular-differentiation
#10
REVIEW
Laura J A Hardwick, Roberta Azzarelli, Anna Philpott
Embryogenesis requires an exquisite regulation of cell proliferation, cell cycle withdrawal and differentiation into a massively diverse range of cells at the correct time and place. Stem cells also remain to varying extents in different adult tissues, acting in tissue homeostasis and repair. Therefore, regulated proliferation and subsequent differentiation of stem and progenitor cells remains pivotal throughout life. Recent advances have characterised the cell cycle dynamics, epigenetics, transcriptome and proteome accompanying the transition from proliferation to differentiation, revealing multiple bidirectional interactions between the cell cycle machinery and factors driving differentiation...
September 20, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30242120/extracellular-vesicles-translational-challenges-and-opportunities
#11
REVIEW
Hannah Clemmens, Daniel W Lambert
Extracellular vesicles (EVs) are a heterogeneous group of small lipid-enclosed structures with myriad roles in physiology and disease. The recent surge of interest in EVs has led to greater understanding of their biology and appreciation of how they might be utilised as diagnostic and therapeutic tools. There remain, however, a number of challenges that must be overcome before EVs may be used routinely in the clinic. In this review we will discuss the translational potential of EVs and the current technologies available to isolate, purify and analyse EVs and their contents...
September 20, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30242119/the-golgi-architecture-and-cell-sensing
#12
REVIEW
Christian Makhoul, Prajakta Gosavi, Paul A Gleeson
An array of signalling molecules are located at the Golgi apparatus, including phosphoinositides, small GTPases, kinases, and phosphatases, which are linked to multiple signalling pathways. Initially considered to be associated predominantly with membrane trafficking, signalling pathways at the Golgi are now recognised to regulate a diverse range of higher-order functions. Many of these signalling pathways are influenced by the architecture of the Golgi. In vertebrate cells, the Golgi consists of individual stacks fused together into a compact ribbon structure and the function of this ribbon structure has been enigmatic...
September 20, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30242118/emerging-role-of-extracellular-vesicles-in-mediating-cancer-cachexia
#13
REVIEW
Sai V Chitti, Pamali Fonseka, Suresh Mathivanan
Cancer cachexia is a multifactorial metabolic syndrome characterized by the rapid loss of skeletal muscle mass with or without the loss of fat mass. Nearly 50-80% of all cancer patients' experience rapid weight loss results in ∼20% of cancer-related deaths. The levels of pro-inflammatory and pro-cachectic factors were significantly up-regulated in cachexia patients when compared with the patients who were without cachexia. It is becoming evident that these factors work synergistically to induce cancer cachexia...
September 20, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30242117/protein-structure-and-computational-drug-discovery
#14
REVIEW
Tracy L Nero, Michael W Parker, Craig J Morton
The first protein structures revealed a complex web of weak interactions stabilising the three-dimensional shape of the molecule. Small molecule ligands were then found to exploit these same weak binding events to modulate protein function or act as substrates in enzymatic reactions. As the understanding of ligand-protein binding grew, it became possible to firstly predict how and where a particular small molecule might interact with a protein, and then to identify putative ligands for a specific protein site...
September 20, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30242116/lipids-and-lipid-domains-of-the-yeast-vacuole
#15
REVIEW
Takuma Tsuji, Toyoshi Fujimoto
The membrane raft has been a focus of intensive research for the past two decades. Liquid-ordered domains form in artificial liposomes containing sterol and saturated lipids, but their presence in living cell membranes has been controversial. The yeast vacuole is exceptional in that micron-sized raft-like domains form in the stationary phase and under several other conditions. The sterol content of the vacuole in the log phase is much lower than that of liposomes showing liquid-ordered domains, suggesting that sterols may need to be supplied to the vacuole for the raft-like domain formation...
September 20, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30190329/lipids-modulate-the-insertion-and-folding-of-the-nascent-chains-of-alpha-helical-membrane-proteins
#16
REVIEW
Nicola J Harris, Kalypso Charalambous, Heather E Findlay, Paula J Booth
Membrane proteins must be inserted into a membrane and folded into their correct structure to function correctly. This insertion occurs during translation and synthesis by the ribosome for most α-helical membrane proteins. Precisely how this co-translational insertion and folding occurs, and the role played by the surrounding lipids, is still not understood. Most of the work on the influence of the lipid environment on folding and insertion has focussed on denatured, fully translated proteins, and thus does not replicate folding during unidirectional elongation of nascent chains that occurs in the cell...
September 6, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30154099/flavin-transferase-the-maturation-factor-of-flavin-containing-oxidoreductases
#17
REVIEW
Alexander V Bogachev, Alexander A Baykov, Yulia V Bertsova
Flavins, cofactors of many enzymes, are often covalently linked to these enzymes; for instance, flavin adenine mononucleotide (FMN) can form a covalent bond through either its phosphate or isoalloxazine group. The prevailing view had long been that all types of covalent attachment of flavins occur as autocatalytic reactions; however, in 2013, the first flavin transferase was identified, which catalyzes phosphoester bond formation between FMN and Na+ -translocating NADH:quinone oxidoreductase in certain bacteria...
August 28, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30154098/the-structural-basis-of-cystic-fibrosis
#18
REVIEW
Xin Meng, Jack Clews, Eleanor R Martin, Anca D Ciuta, Robert C Ford
CFTR (ABCC7) is a phospho-regulated chloride channel that is found in the apical membranes of epithelial cells, is gated by ATP and the activity of the protein is crucial in the homeostasis of the extracellular liquid layer in many organs [ Annu. Rev. Biochem. (2008) 77 , 701-726; Science (1989) 245 , 1066-1073]. Mutations in CFTR cause the inherited disease cystic fibrosis (CF), the most common inherited condition in humans of European descent [ Science (1989) 245 , 1066-1073; Pflugers Arch. (2007) 453 , 555-567]...
August 28, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30154097/the-molecular-clock-and-evolutionary-timescales
#19
REVIEW
Arong Luo, Simon Y W Ho
The molecular clock provides a valuable means of estimating evolutionary timescales from genetic and biochemical data. Proposed in the early 1960s, it was first applied to amino acid sequences and immunological measures of genetic distances between species. The molecular clock has undergone considerable development over the years, and it retains profound relevance in the genomic era. In this mini-review, we describe the history of the molecular clock, its impact on evolutionary theory, the challenges brought by evidence of evolutionary rate variation among species, and the statistical models that have been developed to account for these heterogeneous rates of genetic change...
August 28, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30154094/inside-job-how-the-escrts-release-hiv-1-from-infected-cells
#20
REVIEW
James H Hurley, A King Cada
Human immunodeficiency virus type 1 (HIV-1) hijacks the host endosomal sorting complex required for transport (ESCRT) proteins in order to release infectious viral particles from the cell. ESCRT recruitment is virtually essential for the production of infectious virus, despite that the main structural protein of HIV-1, Gag, is capable of self-assembling and eventually budding from membranes on its own. Recent data have reinforced the paradigm of ESCRT-dependent particle release while clarifying why this rapid release is so critical...
August 28, 2018: Biochemical Society Transactions
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