Benefits of stable isotope labeling in RNA analysis.
Authors: Asadi-Atoi P, Barraud P, Tisne C, Kellner S Abstract RNAs are key players in life as they connect the genetic code (DNA) with all cellular processes dominated by proteins. They contain a variety of chemical modifications and many RNAs fold into complex structures. Here, we review recent progress in the analysis of RNA modification and structure on the basis of stable isotope labeling techniques. Mass spectrometry (MS) and NMR spectroscopy are the key tools and many break-through developments were made possible by analysis of stable isotope labeled RNA. Therefore, we discuss current stable isotope labeling ...
Source: Biological Chemistry - March 21, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

The Gid-complex: an emerging player in the ubiquitin ligase league.
In conclusion, the vertebrate GID-complex evolved as a versatile ubiquitin ligase complex with functions beyond the regulation of glucose metabolism. PMID: 30893051 [PubMed - as supplied by publisher] (Source: Biological Chemistry)
Source: Biological Chemistry - March 21, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Highly flexible, IgG-shaped, trivalent antibodies effectively target tumor cells and induce T cell-mediated killing.
Authors: Dickopf S, Lauer ME, Ringler P, Spick C, Kern P, Brinkmann U Abstract A novel bispecific antibody format was applied to generate T cell-engaging antibodies. The TriFab format is a trivalent IgG-shaped entity composed of two Fab arms that bind to antigens on the surface of tumor cells, which are linked via flexible peptides to a CD3 binding moiety that replaces the CH2 domains of conventional IgGs. The distinctive feature of these T cell recruiting bispecifics is that their CD3 variable regions are incorporated between domains, rather than N- or C-terminally fused to an Fc or antibody fragments. T cell recr...
Source: Biological Chemistry - March 14, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Sequence selection by FitSS4ASR alleviates ancestral sequence reconstruction as exemplified for geranylgeranylglyceryl phosphate synthase.
Authors: Straub K, Linde M, Kropp C, Blanquart S, Babinger P, Merkl R Abstract For evolutionary studies, but also for protein engineering, ancestral sequence reconstruction (ASR) has become an indispensable tool. The first step of every ASR protocol is the preparation of a representative sequence set containing at most a few hundred recent homologs whose composition determines decisively the outcome of a reconstruction. A common approach for sequence selection consists of several rounds of manual recompilation that is driven by embedded phylogenetic analyses of the varied sequence sets. For ASR of a geranylgeranylg...
Source: Biological Chemistry - March 14, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Characterization and engineering of photoactivated adenylyl cyclases.
Authors: Stüven B, Stabel R, Ohlendorf R, Beck J, Schubert R, Möglich A Abstract Cyclic nucleoside monophosphates (cNMP) serve as universal second messengers in signal transduction across prokaryotes and eukaryotes. As signaling often relies on transiently formed microdomains of elevated second messenger concentration, means to precisely perturb the spatiotemporal dynamics of cNMPs are uniquely poised for the interrogation of the underlying physiological processes. Optogenetics appears particularly suited as it affords light-dependent, accurate control in time and space of diverse cellular processes. Seve...
Source: Biological Chemistry - March 14, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Mitochondria, Apoptosis and Cancer (MAC) 2017.
Authors: Turk B PMID: 30864402 [PubMed - as supplied by publisher] (Source: Biological Chemistry)
Source: Biological Chemistry - March 14, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Complexity of type IV collagens: from network assembly to function.
Authors: Wu Y, Ge G Abstract Collagens form complex networks in the extracellular space that provide structural support and signaling cues to cells. Network-forming type IV collagens are the key structural components of basement membranes. In this review, we discuss how the complexity of type IV collagen networks is established, focusing on collagen α chain selection in type IV collagen protomer and network formation; covalent crosslinking in type IV collagen network stabilization; and the differences between solid-state type IV collagen in the extracellular matrix and soluble type IV collagen fragments. We f...
Source: Biological Chemistry - March 14, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Assay of β-glucosidase 2 (GBA2) activity using lithocholic acid β-3-O-glucoside substrate for cultured fibroblasts and glucosylceramide for brain tissue.
Assay of β-glucosidase 2 (GBA2) activity using lithocholic acid β-3-O-glucoside substrate for cultured fibroblasts and glucosylceramide for brain tissue. Biol Chem. 2018 Dec 01;: Authors: Harzer K, Yildiz Y, Beck-Wödl S Abstract Beta-glucosidase 2 (GBA2) is deficient in a form of human spastic paraplegia due to defects in the GBA2 (SPG46) gene. GBA2 was proposed as a modifier of Gaucher disease (lysosomal storage disease by deficient β-glucosidase 1; GBA1). Described assays of GBA2 activity mostly used artificial substrates incompletely modelling the situation with natural substrate...
Source: Biological Chemistry - March 14, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

The effects of oxidative stress on the development of atherosclerosis.
Authors: Khosravi M, Poursaleh A, Ghasempour G, Farhad S, Najafi M Abstract Atherosclerosis is a cardiovascular disease known widely in the world. Several hypothesizes are suggested to be involved in the narrowing of arteries during process of atherogenesis. The oxidative modification hypothesis is related to oxidative and anti-oxidative imbalance and is most investigated. The aim of this study was to review the role of oxidative stress in atherosclerosis. Furthermore, it describes the roles of oxidative/anti-oxidative enzymes and compounds in the macromolecular and lipoprotein modifications and triggering the infl...
Source: Biological Chemistry - March 14, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Long non-coding RNA CHRF promotes proliferation and mesenchymal transition (EMT) in prostate cancer cell line PC3 requiring up-regulating microRNA-10b.
Authors: Liu C, Wang L, Li Y, Cui Y, Wang Y, Liu S Abstract Despite the advance of diagnosis and treatment for prostate cancer, the prognosis of metastatic prostate cancer is poor. We aimed to explore the functional role of long non-coding RNA cardiac hypertrophy-related factor (lncRNA CHRF) in prostate cancer cells (PC3) as well as the molecular mechanisms. LncRNA CHRF silence repressed cell number (%), downregulated expression of cyclinD1, CDK4 and CDK6, and promoted apoptosis along with activation of the casapse-3 and caspase-9. LncRNA CHRF promoted mesenchymal transition (EMT), showing down-regulation of E-cadh...
Source: Biological Chemistry - March 8, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Transient receptor potential channels in the context of nociception and pain - recent insights into TRPM3 properties and function.
Authors: Behrendt M Abstract Potential harmful stimuli like heat, mechanical pressure or chemicals are detected by specialized cutaneous nerve fiber endings of nociceptor neurons in a process called nociception. Acute stimulation results in immediate protective reflexes and pain sensation as a normal, physiological behavior. However, ongoing (chronic) pain is a severe pathophysiological condition with diverse pathogeneses that is clinically challenging because of limited therapeutic options. Therefore, an urgent need exists for new potent and specific analgesics without afflicting adverse effects. Recently, TRPM3, ...
Source: Biological Chemistry - March 8, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Indigoid dyes by group E monooxygenases: mechanism and biocatalysis.
In this study, group E monooxygenases (styrene monooxygenase and indole monooxygenase) were used for the selective oxygenation of indole (derivatives). It was possible for the first time to show that the product of the enzymatic reaction is an epoxide. Further, we synthesized and extracted indigoid dyes and could show that there is only minor by-product formation (e.g. indirubin or isoindigo). Thus, group E monooxygenase can be an alternative biocatalyst for the biosynthesis of indigoid dyes. PMID: 30844759 [PubMed - as supplied by publisher] (Source: Biological Chemistry)
Source: Biological Chemistry - March 8, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Regulation and related mechanism of GSN mRNA level by hnRNPK in lung adenocarcinoma cells.
Authors: Liu XH, Ma J, Feng JX, Zhang YF, Liu L Abstract Gelsolin (GSN) is an actin filament-capping protein that plays a key role in cell migration. Here we showed that heterogeneous nuclear ribonucleoprotein K (hnRNPK) regulates GSN expression level by binding to the 3'-untranslated region (3'UTR) of GSN mRNA in non-small cell lung cancers (NSCLC) H1299 cells which are highly metastatic and express high level of GSN. We found that hnRNPK overexpression increased the mRNA and protein level of GSN, whereas hnRNPK knockdown by siRNA decreased the mRNA and protein level of GSN in both H1299 and A549 cells, indicating...
Source: Biological Chemistry - February 18, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Highly flexible, IgG-shaped, trivalent antibodies effectively target tumor cells and induce T cell-mediated killing.
Authors: Dickopf S, Lauer ME, Ringler P, Spick C, Kern P, Brinkmann U Abstract A novel bispecific antibody format was applied to generate T cell-engaging antibodies. The TriFab format is a trivalent IgG-shaped entity composed of two Fab arms that bind to antigens on the surface of tumor cells, which are linked via flexible peptides to a CD3 binding moiety that replaces the CH2 domains of conventional IgGs. The distinctive feature of these T cell recruiting bispecifics is that their CD3 variable regions are incorporated between domains, rather than N- or C-terminally fused to an Fc or antibody fragments. T cell recr...
Source: Biological Chemistry - February 15, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Sequence selection by FitSS4ASR alleviates ancestral sequence reconstruction as exemplified for geranylgeranylglyceryl phosphate synthase.
Authors: Straub K, Linde M, Kropp C, Blanquart S, Babinger P, Merkl R Abstract For evolutionary studies, but also for protein engineering, ancestral sequence reconstruction (ASR) has become an indispensable tool. The first step of every ASR protocol is the preparation of a representative sequence set containing at most a few hundred recent homologs whose composition determines decisively the outcome of a reconstruction. A common approach for sequence selection consists of several rounds of manual recompilation that is driven by embedded phylogenetic analyses of the varied sequence sets. For ASR of a geranylgeranylg...
Source: Biological Chemistry - February 15, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Characterization and engineering of photoactivated adenylyl cyclases.
Authors: Stüven B, Stabel R, Ohlendorf R, Beck J, Schubert R, Möglich A Abstract Cyclic nucleoside monophosphates (cNMP) serve as universal second messengers in signal transduction across prokaryotes and eukaryotes. As signaling often relies on transiently formed microdomains of elevated second messenger concentration, means to precisely perturb the spatiotemporal dynamics of cNMPs are uniquely poised for the interrogation of the underlying physiological processes. Optogenetics appears particularly suited as it affords light-dependent, accurate control in time and space of diverse cellular processes. Seve...
Source: Biological Chemistry - February 15, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Nm23-H1 inhibits hypoxia induced epithelial-mesenchymal transition and stemness in non-small cell lung cancer cells.
In this study, nm23-H1 was down regulated in epithelial-mesenchymal transition (EMT) and stemness enhancement under cobalt chloride (CoCl2)-induced hypoxia in NSCLC cells. Moreover, knocking down of nm23-H1 by shRNA apparently promoted hypoxia induced EMT and stemness, which was entirely suppressed via over expression of nm23-H1. Mechanistically, the Wnt/β-catenin signaling pathway was found to participate in the nm23-H1-mediated process. Besides, XAV939 prohibited cell EMT and stemness which could be impaired by knocking down of nm23-H1, while stable transfection of nm23-H1 attenuated hypoxia phonotype induced by lit...
Source: Biological Chemistry - February 15, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Zinc-induced activation of GPR39 regulates glucose homeostasis through glucose-dependent insulinotropic polypeptide secretion from enteroendocrine K-cells.
Authors: Moran BM, Miskelly MG, Abdel-Wahab YHA, Flatt PR, McKillop AM Abstract The role of Zn2+-sensing receptor GPR39 on glucose homeostasis and incretin regulation was assessed in enteroendocrine L- and K-cells. Anti-hyperglycaemic, insulinotropic and incretin secreting properties of Zn2+ were explored in normal, diabetic and incretin receptor knockout mice. Compared to intraperitoneal injection, oral administration of Zn2+ (50 μmol/kg body weight) with glucose (18 mmol/kg) in lean mice reduced the glycaemic excursion by 25-34% (p
Source: Biological Chemistry - February 11, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Metalloprotease inhibitor profiles of human ADAM8 in vitro and in cell-based assays.
Authors: Schlomann U, Dorzweiler K, Nuti E, Tuccinardi T, Rossello A, Bartsch JW Abstract ADAM8 as a membrane-anchored metalloproteinase-disintegrin is upregulated under pathological conditions such as inflammation and cancer. As active sheddase, ADAM8 can cleave several membrane proteins, among them the low-affinity receptor FcεRII CD23. Hydroxamate-based inhibitors are routinely used to define relevant proteinases involved in ectodomain shedding of membrane proteins. However, for ADAM proteinases, common hydroxamates have variable profiles in their inhibition properties, commonly known for ADAM proteinase...
Source: Biological Chemistry - February 11, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

LncRNA HOTAIR targets miR-126-5p to promote the progression of Parkinson's disease through RAB3IP.
In this study, we aimed to further illustrate the molecular mechanism of HOTAIR in PD. Bioinformatics analysis was utilized to determine the potential downstream targets of HOTAIR in PD. Luciferase assay and RNA Binding Protein Immunoprecipitation (RIP) assay were used to validate the existence of binding sites between competing endogenous RNAs (ceRNAs). Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting indicated that HOTAIR and RAB3IP increased while miR-126-5p decreased in PD cells and PD mice. Additionally, CCK- 8 assay and flow cytometric analysis indicated that the knockdown of HOTAIR and...
Source: Biological Chemistry - February 11, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

CFTR structure, stability, function and regulation.
Authors: Meng X, Clews J, Cuitaa AD, Martin ER, Ford RC Abstract CFTR (Cystic Fibrosis transmembrane conductance regulator) is a unique member of the ATP-binding cassette family of proteins because it has evolved into a channel. Mutations in CFTR cause cystic fibrosis, the most common genetic disease in people of European origins. The F508del mutation is found in about 90% of patients and here we present data that suggest its main effect is on CFTR stability rather than on the 3D folded state. A survey of recent cryo-electron microscopy studies was carried out and this highlighted differences in terms of CFTR confo...
Source: Biological Chemistry - February 11, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

ABCB4 / MDR3 in health and disease - at the crossroads of biochemistry and medicine.
Authors: Prescher M, Kroll T, Schmitt L Abstract Several ABC transporters of the human liver are responsible for the secretion of bile salts, lipids and cholesterol. Their interplay protects the biliary tree from the harsh detergent activity of bile salts. Among these transporters, ABCB4 is essential for the translocation of phosphatidylcholine lipids from the inner to the outer leaflet of the canalicular membrane of hepatocytes. ABCB4 deficiency can result in altered phosphatidylcholine to bile salt ratios, which led to intrahepatic cholestasis of pregnancy, low phospholipid associated cholelithiasis, drug induced...
Source: Biological Chemistry - February 10, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Molecular effects of dietary fatty acids on brain insulin action and mitochondrial function.
Authors: Chudoba C, Wardelmann K, Kleinridders A Abstract The prevalence of obesity and its co-morbidities such as insulin resistance and type 2 diabetes are tightly linked to increased ingestion of palatable fat enriched food. Thus, it seems intuitive that the brain senses elevated amounts of fatty acids and affects adaptive metabolic response, which is connected to mitochondrial function and insulin signaling. This review will address the effect of dietary fatty acids on brain insulin and mitochondrial function with a special emphasis on the impact of different fatty acids on brain function and metabolism. PM...
Source: Biological Chemistry - February 10, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Nodal promotes the malignancy of non-small cell lung cancer (NSCLC) cells via activation of NF- κB/IL-6 signals.
Nodal promotes the malignancy of non-small cell lung cancer (NSCLC) cells via activation of NF-κB/IL-6 signals. Biol Chem. 2018 Dec 01;: Authors: Xu X, Zhou X, Gao C, Cao L, Zhang Y, Hu X, Cui Y Abstract Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer deaths worldwide. Understanding the mechanisms responsible for the malignancy of NSCLC cell is important for therapy and drug development. Nodal, an important embryonic morphogen, has been reported to modulate tumorigenesis. We found that Nodal can trigger the proliferation of NSCLC cells and decrease the sensitivity to dox...
Source: Biological Chemistry - February 1, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

MCT1, MCT4 and CD147 expression and 3-bromopyruvate toxicity in colorectal cancer cells are modulated by the extracellular conditions.
Authors: Pereira-Vieira J, Azevedo-Silva J, Preto A, Casal M, Queirós O Abstract Monocarboxylate transporters (MCTs) inhibition leads to disruption in glycolysis, induces cell death and decreases cell invasion, revealing the importance of MCT activity in intracellular pH homeostasis and tumor aggressiveness. 3-bromopyruvate (3BP) is an antitumor agent, whose uptake occurs via MCTs. It was aim of this work to unravel the importance of extracellular conditions on MCTs regulation and in 3BP activity. HCT-15 was found to be the most sensitive cell line and also the one that presented the highest basal expression...
Source: Biological Chemistry - February 1, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Protein engineering comes of age.
Authors: Kolmar H Abstract No abstract available. PMID: 30703059 [PubMed - as supplied by publisher] (Source: Biological Chemistry)
Source: Biological Chemistry - February 1, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Computational design of structured loops for new protein functions.
Authors: Kundert K, Kortemme T Abstract The ability to engineer the precise geometries, fine-tuned energetics and subtle dynamics that are characteristic of functional proteins is a major unsolved challenge in the field of computational protein design. In natural proteins, functional sites exhibiting these properties often feature structured loops. However, unlike the elements of secondary structures that comprise idealized protein folds, structured loops have been difficult to design computationally. Addressing this shortcoming in a general way is a necessary first step towards the routine design of protein functi...
Source: Biological Chemistry - January 26, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Changqin NO. 1 inhibits neuronal apoptosis via suppressing GAS5 expression in traumatic brain injury mice model.
Authors: Dai X, Yi M, Wang D, Chen Y, Xu X Abstract The present study was designed to investigate the mechanism of traditional Chinese medicine Changqin NO. 1 on amelioration of traumatic brain injury (TBI). Adult male C57BL/6J mice and newborn mice were used to generate a mouse TBI model and harvest primary neurons, respectively. The localizations of specific neural markers neuropilin-1 (Nrp-1), growthassociated protein-43 (GAP-43) and microtubule-associated protein Tau (Tau) were examined in brain tissues by immunohistochemistry. TUNEL apoptotic cell detection in tissue sections and CCK-8 cell viability assay wer...
Source: Biological Chemistry - January 19, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Chemical modification of neuropeptide Y for human Y1 receptor targeting in health and disease.
Authors: Hofmann S, Bellmann-Sickert K, Beck-Sickinger AG Abstract As a very abundant neuropeptide in the brain and widely distributed peptide hormone in the periphery, neuropeptide Y (NPY) appears to be a multisignaling key peptide. Together with peptide YY, pancreatic polypeptide and the four human G protein-coupled receptor subtypes hY1R, hY2R, hY4R and hY5R it forms the NPY/hYR multiligand/multireceptor system, which is involved in essential physiological processes as well as in human diseases. In particular, NPY-induced hY1R signaling plays a central role in the regulation of food intake and stress response as...
Source: Biological Chemistry - January 19, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

The conserved theme of ribosome hibernation: from bacteria to chloroplasts of plants.
Authors: Trösch R, Willmund F Abstract Cells are highly adaptive systems that respond and adapt to changing environmental conditions such as temperature fluctuations or altered nutrient availability. Such acclimation processes involve reprogramming of the cellular gene-expression profile, tuning of protein synthesis, remodelling of metabolic pathways and morphological changes of the cell shape. Nutrient starvation can lead to limited energy supply and consequently, remodelling of protein synthesis is one of the key steps of regulation since the translation of the genetic code into functional polypeptides may c...
Source: Biological Chemistry - January 19, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Organic anion transporter 1 and 3 influence cellular energy metabolism in renal proximal tubule cells.
In conclusion, our results indicate an increased α-ketoglutarate efflux by OAT1 and OAT3, resulting in a metabolic shift towards an oxidative phenotype. PMID: 30653465 [PubMed - as supplied by publisher] (Source: Biological Chemistry)
Source: Biological Chemistry - January 19, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

Hit evaluation of an α-helical peptide: Ala-scan, truncation, and sidechain-to-sidechain macrocyclization of an RNA polymerase Inhibitor.
Hit evaluation of an α-helical peptide: Ala-scan, truncation, and sidechain-to-sidechain macrocyclization of an RNA polymerase Inhibitor. Biol Chem. 2018 Dec 01;: Authors: Kamal AAM, Habib M, Haupenthal J, Hartmann RW, Empting M Abstract RNA polymerase (RNAP) remains a relatively underexplored target with only rifampicin and fidaxomicin in clinical use. Hence, the concurrent rise in bacterial resistance rate urges the search for novel RNAP inhibitors with novel mode of action. In this work, we investigated the impact of several systematic modifications including sidechain-to-sidechain macrocyliza...
Source: Biological Chemistry - January 19, 2019 Category: Chemistry Tags: Biol Chem Source Type: research

An engineered lipocalin that tightly complexes the plant poison colchicine for use as antidote as well as bioanalytical applications.
Authors: Skerra A, Barkovskiy M, Ilyukhina E, Dauner M, Eichinger A Abstract Colchicine is a toxic alkaloid prevalent in autumn crocus (Colchicum autumnale) that binds to tubulin and inhibits polymerization of microtubules. Using combinatorial and rational protein design, we have developed an artificial binding protein based on the human lipocalin 2 that binds colchicine with a dissociation constant of 120 pM, i.e. 10 000-fold stronger than tubulin. Crystallographic analysis of the engineered lipocalin, dubbed Colchicalin, revealed major structural changes in the flexible loop region that forms the ligand pocket at...
Source: Biological Chemistry - December 7, 2018 Category: Chemistry Tags: Biol Chem Source Type: research

Differential expression of DLG1 as a common trait in different human diseases: an encouraging issue in molecular pathology.
Authors: Gardiol D, Marziali F, Dizanzo MP, Cavatorta AL Abstract Human Disc large (DLG1) is a scaffolding protein that through the interaction with diverse cell partners participates in the control of key cellular processes such as polarity, proliferation and migration. Experimental data have mainly identified DLG1 as a tumor suppressor. An outstanding point for DLG1 protein is that altered DLG1 expression and DLG1 gene mutations were observed in different pathologies, including cancer and neurological and immunological disorders. Evident changes in DLG1 abundance and/or cell localization were identified in a numb...
Source: Biological Chemistry - December 7, 2018 Category: Chemistry Tags: Biol Chem Source Type: research

Peptide binding affinity redistributes preassembled repeat protein fragments.
Authors: Michel E, Zerbe O, Plückthun A Abstract Designed armadillo repeat proteins (dArmRPs) are modular peptide binders composed of N- and C-terminal capping repeats Y and A and a variable number of internal modules M that each specifically recognize two amino acids of the target peptide. Complementary fragments of dArmRPs obtained by splitting the protein between helices H1 and H2 of an internal module show conditional and specific assembly only in presence of a target peptide (Michel et al., 2018). Here, we investigate dArmRP fragments that already spontaneously assemble with high affinity, e.g. those obta...
Source: Biological Chemistry - December 7, 2018 Category: Chemistry Tags: Biol Chem Source Type: research

The comparative biochemistry of viruses and humans: an evolutionary path towards autoimmunity.
Authors: Kanduc D Abstract Analyses of the peptide sharing between five common human viruses (Borna disease virus, influenza A virus, measles virus, mumps virus and rubella virus) and the human proteome highlight a massive viral vs. human peptide overlap that is mathematically unexpected. Evolutionarily, the data underscore a strict relationship between viruses and the origin of eukaryotic cells. Indeed, according to the viral eukaryogenesis hypothesis and in light of the endosymbiotic theory, the first eukaryotic cell (our lineage) originated as a consortium consisting of an archaeal ancestor of the eukaryotic cyt...
Source: Biological Chemistry - December 7, 2018 Category: Chemistry Tags: Biol Chem Source Type: research

LncRNA TINCR / microRNA-107 / CD36 regulates cell proliferation and apoptosis in colorectal cancer via PPAR signaling pathway based on bioinformatics analysis.
Authors: Zhang X, Yao J, Shi H, Gao B, Zhang L Abstract Present study aims to determine the potential biomarkers and uncover the regulatory mechanisms of lncRNA TINCR / miR-107 / CD36 axis in CRC. Aberrantly expressed lncRNAs and differential-expressed genes were identified by analyzing the dataset GSE40967. Gene set enrichment analysis were employed, and Cytoscape software helps establishing the co-expression network between lncRNAs and genes. Quantitative RT-PCR analysis contributes to examining the expression levels of lncRNA TINCR, miR-107 and CD36. Dual luciferase assay was used to validate the association bet...
Source: Biological Chemistry - December 7, 2018 Category: Chemistry Tags: Biol Chem Source Type: research

Directed evolution of the 3C protease from Coxsackievirus using a novel fluorescence-assisted intracellular method.
This reporter consists of an aggregation-prone peptide fused to a fluorescent protein via a linker that contains the corresponding substrate sequence. Cleavage of the substrate rescues the fluorescent protein from aggregation, resulting in increased fluorescence that correlates to proteolytic activity, which can be monitored using flow cytometry. In one round of flow-cytometric cell sorting, we isolated an efficiently cleaved TEV substrate from a 1:100,000 background of non-cleavable sequences, with around 6000- fold enrichment. We then engineered the 3C protease from Coxsackievirus B3 (CVB3 3Cpro) towards improved proteol...
Source: Biological Chemistry - December 7, 2018 Category: Chemistry Tags: Biol Chem Source Type: research

Kinetically selective and potent inhibitors of HDAC8.
Authors: Schweipert M, Jänsch N, Sugiarto WO, Meyer-Almes FJ Abstract HDAC8 is an established and validated target for T-cell lymphoma and childhood neuroblastoma. The active site binding pocket of HDAC8 is highly conserved among all zinccontaining representatives of the histone deacetylase family. This explains that most HDACs are unselectively recognized by similar inhibitors featuring a zinc binding group (ZBG), a hydrophobic linker and a head group. In the light of this difficulty, the creation of isoenzymeselectivity is one of the major challenges in the development of HDAC inhibitors. In a series of trif...
Source: Biological Chemistry - December 7, 2018 Category: Chemistry Tags: Biol Chem Source Type: research

Shining light on plant hormones with genetically encoded biosensors.
Authors: Martin-Arevalillo R, Vernoux T Abstract Signalling molecules are produced, degraded, modified and transported throughout the development of higher organisms. Understanding their mode of action implies understanding these dynamics in vivo and in real time. Genetically encoded biosensors are being more and more used as tools to 'follow' signalling molecules and their responses inside an organism. This is the case for plants, where important progresses have been made in the development of such biosensors. Here, we summarize the main genetically encoded biosensors built for plant hormones, constructed using di...
Source: Biological Chemistry - December 6, 2018 Category: Chemistry Tags: Biol Chem Source Type: research

Synthetic biology of B cell activation: understanding signal amplification at the B cell antigen receptor using a rebuilding approach.
Authors: Kulathu Y, Zuern C, Yang J, Reth M Abstract Upon activation of the B cell antigen receptor (BCR), the spleen tyrosine kinase (Syk) and the Src family kinase Lyn phosphorylate tyrosines of the immunoreceptor tyrosine-based activation motif (ITAM) of Igα and Igβ which further serve as binding sites for the SH2 domains of these kinases. Using a synthetic biology approach, we dissect the roles of different ITAM residues of Igα in Syk activation. We find that a leucine to glycine mutation at the Y+3 position after the first ITAM tyrosine prevents Syk binding and activation. However, a preactiva...
Source: Biological Chemistry - November 23, 2018 Category: Chemistry Tags: Biol Chem Source Type: research

Unforgettable force - crosstalk and memory of mechanosensitive structures.
Authors: Kanoldt V, Fischer L, Grashoff C Abstract The ability of cells to sense and respond to mechanical stimuli is crucial for many developmental and homeostatic processes, while mechanical dysfunction of cells has been associated with numerous pathologies including muscular dystrophies, cardiovascular defects, and epithelial disorders. Yet, how cells detect and process mechanical information is still unclear. In this review, we outline major mechanisms underlying cellular mechanotransduction and we summarize the current understanding of how cells integrate information from distinct mechanosensitive structures t...
Source: Biological Chemistry - November 23, 2018 Category: Chemistry Tags: Biol Chem Source Type: research

Facile generation of antibody heavy and light chain diversities for yeast surface display by Golden Gate Cloning.
Authors: Roth L, Grzeschik J, Hinz SC, Becker S, Toleikis L, Busch M, Kolmar H, Krah S, Zielonka S Abstract Antibodies can be successfully engineered and isolated by yeast or phage display of combinatorial libraries. Still, generation of libraries comprising heavy chain as well as light chain diversities is a cumbersome process involving multiple steps. Within this study, we set out to compare the output of yeast display screening of antibody Fab libraries from immunized rodents that were generated by Golden Gate Cloning with the conventional three step method of individual heavy- and light chain sub-library constr...
Source: Biological Chemistry - November 23, 2018 Category: Chemistry Tags: Biol Chem Source Type: research

Conversion of chenodeoxycholic acid to cholic acid by human CYP8B1.
In this study we demonstrate that CYP8B1 can also convert CDCA itself to CA. We also show that five derivatives of luciferin are metabolized by CYP8B1 and established a rapid and convenient inhibitor test system. In this way we were able to identify four new CYP8B1 inhibitors, which are aminobenzotriazole, exemestane, ketoconazole, and letrozole. PMID: 30465713 [PubMed - as supplied by publisher] (Source: Biological Chemistry)
Source: Biological Chemistry - November 23, 2018 Category: Chemistry Tags: Biol Chem Source Type: research

Stimulation of Melanin Synthesis in Melanoma Cells by Cold Plasma.
This study investigated melanin biosynthesis of human melanoma cell lines with different endogenous melanin contents (SK-Mel 28, G-361, FM55 and MNT-1) in response to cold plasma-derived reactive species. Initially, the distribution of melanosomes, via immunofluorescence, and the influence of microphthalmia-associated transcription factor (MiTF), as a key transcription factor, was investigated. In our experimental setup, all of the tested cell lines had an elevated melanin content after exposure to cold plasma. These promising results suggest a novel potential application of cold plasma for the regulation of melanogenesis ...
Source: Biological Chemistry - November 9, 2018 Category: Chemistry Tags: Biol Chem Source Type: research

Chemistry and Biochemistry of Cold Physical Plasma Derived Reactive Species in Liquids.
Authors: Wende K, Woedtke TV, Weltmann KD, Bekeschus S Abstract Reactive oxygen and nitrogen species deposited by cold physical plasma are proposed as predominant effectors in the interaction between discharge and biomedical application. Most reactive species found in plasma sources are known in biology for inter- and intracellular communication (redox signaling) and mammalian cells are equipped to interpret the plasma derived redox signal. Such, considerable effort has been put on the investigation of potential clinical applications and the underlying mechanism, with a special emphasis on conditions orchestrated s...
Source: Biological Chemistry - November 9, 2018 Category: Chemistry Tags: Biol Chem Source Type: research

Rational Design of an Improved Photo-Activatable Intein for the Production of Head-To-Tail Cyclized Peptides.
Authors: Böcker JK, Dörner W, Mootz HD Abstract Head-to-tail cyclization of genetically encoded peptides and proteins can be achieved with the SICLOPPS method by inserting the desired polypeptide between the C- and N-terminal fragments of a split intein. To prevent the intramolecular protein splicing reaction from spontaneously occurring upon folding of the intein domain, we have previously rendered this process light-dependent in a photo-controllable variant of the M86 intein, using genetically encoded ortho-nitrobenzyltyrosine at a structurally important position. Here we report improvements on this pho...
Source: Biological Chemistry - November 9, 2018 Category: Chemistry Tags: Biol Chem Source Type: research

Highlight Issue: Plasma Medicine.
Authors: Schmidt A, Woedtke TV Abstract No abstract available. PMID: 30403652 [PubMed - as supplied by publisher] (Source: Biological Chemistry)
Source: Biological Chemistry - November 9, 2018 Category: Chemistry Tags: Biol Chem Source Type: research

Regulatory effect of hsa-miR-5590-3P on TGF β signaling through targeting of TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 transcripts.
Regulatory effect of hsa-miR-5590-3P on TGFβ signaling through targeting of TGFβ-R1, TGFβ-R2, SMAD3 and SMAD4 transcripts. Biol Chem. 2018 Nov 01;: Authors: Bakhshmand EA, Soltani BM Abstract Transforming growth factor-β (TGFβ) signaling acts as suppressor and inducer of tumor progression during early and late stages of cancer, respectively. Some miRNAs have shown regulatory effect on TGFβ signaling and here, we have used combination of bioinformatics and experimental tools to show that hsa-miR-5590-3p is a regulator of multiple genes expression in TGFβ signaling path...
Source: Biological Chemistry - November 6, 2018 Category: Chemistry Tags: Biol Chem Source Type: research

Differential involvement of TAK1, RIPK1 and NF- κB signaling in Smac mimetic-induced cell death in breast cancer cells.
In conclusion, TAK1, receptor-interacting kinase 1 (RIPK1) as well as canonical and non-canonical NF-κB signaling are differentially involved in SM-induced cell death in breast cancer cells. These findings contribute to a better understanding of SM-induced signaling pathways. PMID: 30391931 [PubMed - as supplied by publisher] (Source: Biological Chemistry)
Source: Biological Chemistry - November 6, 2018 Category: Chemistry Tags: Biol Chem Source Type: research