3,663 results match your criteria Biological chemistry[Journal]


19F NMR as a versatile tool to study (membrane) protein structure and dynamics.

Biol Chem 2018 Dec 1. Epub 2018 Dec 1.

Institute for Pharmacy and Biochemistry, Johannes Gutenberg University, Johann-Joachim- Becher-Weg 30, D-55128 Mainz, Germany.

To elucidate the structures and dynamics of membrane proteins, highly advanced biophysical methods have been developed that often require significant resources, both for sample preparation and experimental analyses. For very complex systems, such as membrane transporters, ion channels or GPCRs, the incorporation of a single reporter at a select site can significantly simplify the observables and the measurement/analysis requirements. Here we present examples using 19F NMR spectroscopy as a powerful, yet relatively straightforward tool to study (membrane) protein structure, dynamics and ligand interactions. Read More

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http://www.degruyter.com/view/j/bchm.just-accepted/hsz-2018-
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http://dx.doi.org/10.1515/hsz-2018-0473DOI Listing
December 2018
1 Read

Retrograde response by reactive oxygen/nitrogen species in plants involving different cellular organelles.

Biol Chem 2018 Dec 1. Epub 2018 Dec 1.

Department of Metabolic and Structural Biology, Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow226015,India.

During oxidative and nitrosative stress conditions cellular organelles convey information to the nucleus to express specific sets of genes to withstand the stress condition and to reorganize their growth and developmental pattern. This organelle to nucleus communication is termed as retrograde signaling. In plant system chloroplast and peroxisomes are mainly involved with little involvement of mitochondria and other organelles in oxidative stress-mediated retrograde signaling. Read More

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http://dx.doi.org/10.1515/hsz-2018-0463DOI Listing
December 2018

Posttranslational modifications and proteinopathies: how guardians of the proteome are defeated.

Authors:
Heidi Olzscha

Biol Chem 2018 Dec 1. Epub 2018 Dec 1.

Institut für Physiologische Chemie, Medizinische Fakultät, Martin-Luther-Universität Halle- Wittenberg, Hollystr. 1, D-06114 Halle/Saale, Germany.

Protein folding is one of the fundamental processes in life, and therefore needs to be tightly regulated. Many cellular quality control systems are in place to ensure that proteostasis is optimally adjusted for a changing environment, facilitating protein folding, translocation and degradation. These systems include the molecular chaperones and the major protein degradation systems, namely the ubiquitin proteasome system and autophagy. Read More

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http://dx.doi.org/10.1515/hsz-2018-0458DOI Listing
December 2018

Vimentin is required for normal accumulation of body fat.

Biol Chem 2019 Apr 1. Epub 2019 Apr 1.

Laboratory of Astrocyte Biology and CNS Regeneration, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Box 440, S-40530 Gothenburg, Sweden.

Intermediate filaments (nanofilaments) have many functions, especially in response to cellular stress. Mice lacking vimentin (Vim-/-) display phenotypes reflecting reduced levels of cell activation and ability to counteract stress, e.g. Read More

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http://www.degruyter.com/view/j/bchm.just-accepted/hsz-2019-
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http://dx.doi.org/10.1515/hsz-2019-0170DOI Listing
April 2019
1 Read

Mass spectrometry of membrane protein complexes.

Biol Chem 2019 Apr 8. Epub 2019 Apr 8.

Interdisciplinary Research Center HALOmem, Charles Tanford Protein Centre, Martin Luther University Halle-Wittenberg, Institute for Biochemistry and Biotechnology, Kurt-Mothes-Str. 3a, D-06120 Halle, Germany.

Membrane proteins are key players in the cell. Due to their hydrophobic nature they require solubilising agents such as detergents or membrane mimetics during purification and, consequently, are challenging targets in structural biology. In addition, their natural lipid environment is crucial for their structure and function further hampering their analysis. Read More

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http://dx.doi.org/10.1515/hsz-2018-0443DOI Listing

Sub-membranous actin rings in the axon initial segment are resistant to the action of latrunculin.

Biol Chem 2019 Apr 5. Epub 2019 Apr 5.

Minerva Foundation Institute for Medical Research, Biomedicum Helsinki 2U, Tukholmankatu 8, 00290 Helsinki, Finland.

The axon initial segment (AIS) comprises a sub-membranous lattice containing periodic actin rings. The overall AIS structure is insensitive to actin-disrupting drugs, but the effects of actin-disrupting drugs on actin rings lack consensus. We examined the effect of latrunculin A and B on the actin cytoskeleton of neurons in culture and actin rings in the AIS. Read More

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http://dx.doi.org/10.1515/hsz-2019-0111DOI Listing
April 2019
1 Read

S. aureus α-toxin: small pore, large consequences.

Biol Chem 2018 Dec 1. Epub 2018 Dec 1.

Institute for Pharmacy and Biochemistry, Johannes Gutenberg-University Mainz, Johann- Joachim Becher-Weg 30, 55128 Mainz, Germany.

The small β-pore-forming α-toxin, also termed α-hemolysin or Hla is considered to be an important virulence factor of S. aureus. Perforation of the plasma membrane (PM) by Hla leads to uncontrolled flux of ions and water. Read More

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http://dx.doi.org/10.1515/hsz-2018-0472DOI Listing
December 2018
4 Reads

Ageing and sources of transcriptional heterogeneity.

Biol Chem 2019 Apr 22. Epub 2019 Apr 22.

Max Planck Research Group 'Chromatin and Ageing', Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, D-50931 Cologne, Germany.

Cellular heterogeneity is an important contributor to biological function and is employed by cells, tissues and organisms to adapt, compensate, respond, defend and/or regulate specific processes. Research over the last decades has revealed that transcriptional noise is a major driver for cell-to-cell variability. In this review we will discuss sources of transcriptional variability, in particular bursting of gene expression and how it could contribute to cellular states and fate decisions. Read More

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http://dx.doi.org/10.1515/hsz-2018-0449DOI Listing
April 2019
5 Reads

Mg2+ homeostasis and transport in cyanobacteria - at the crossroads of bacterial and chloroplast Mg2+ import.

Biol Chem 2019 Apr 22. Epub 2019 Apr 22.

Institut für Pharmazie und Biochemie, Johannes-Gutenberg-Universität Mainz, Johann-Joachim-Becher-Weg 30, D-55128 Mainz, Germany.

Magnesium cation (Mg2+) is the most abundant divalent cation in living cells, where it is required for various intracellular functions. In chloroplasts and cyanobacteria, established photosynthetic model systems, Mg2+ is the central ion in chlorophylls, and Mg2+ flux across the thylakoid membrane is required for counterbalancing the light-induced generation of a ΔpH across the thylakoid membrane. Yet, not much is known about Mg2+ homoeostasis, transport and distribution within cyanobacteria. Read More

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http://dx.doi.org/10.1515/hsz-2018-0476DOI Listing

Tripterine inhibits proliferation, migration and invasion of breast cancer MDA-MB-231 cells by up-regulating microRNA-15a.

Biol Chem 2019 Apr 22. Epub 2019 Apr 22.

Department of Breast Surgery, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao 266000, China.

Breast cancer is the most commonly diagnosed cancer in women worldwide. Tripterine is an important active component isolated from Triperygium wilfordii Hook F. This study investigated the effects of tripterine on breast cancer cell proliferation, migration, invasion and apoptosis, as well as microRNA-15a (miR-15a) expression. Read More

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http://dx.doi.org/10.1515/hsz-2018-0469DOI Listing
April 2019
2 Reads

The multifaceted roles of tumor-associated proteases and harnessing their activity for prodrug activation.

Biol Chem 2019 Apr 22. Epub 2019 Apr 22.

CytomX Therapeutics Inc., Platform Biology, 151 Oyster Point Blvd, South San Francisco, CA 94080, USA.

The role of proteases in cancer was originally thought to be limited to the breakdown of basement membranes and extracellular matrix (ECM), thereby promoting cancer cell invasion into surrounding normal tissues. It is now well understood that proteases play a much more complicated role in all stages of cancer progression and that not only tumor cells, but also stromal cells are an important source of proteases in the tumor microenvironment. Among all the proteolytic enzymes potentially associated with cancer, some proteases have taken on heightened importance due to their significant up-regulation and ability to participate at multiple stages of cancer progression and metastasis. Read More

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http://dx.doi.org/10.1515/hsz-2018-0451DOI Listing

Aryl hydrocarbon receptor ligands increase ABC transporter activity and protein expression in killifish (Fundulus heteroclitus) renal proximal tubules.

Biol Chem 2019 Apr 22. Epub 2019 Apr 22.

Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-University, D-69120 Heidelberg, Germany.

Many widespread and persistent organic pollutants, for example, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and some polychlorinated biphenyls, activate the aryl hydrocarbon receptor (AhR) causing it to translocate to the cell nucleus where it transactivates target genes, increasing expression of a number of xenobiotic metabolizing enzymes as well as some transporters. AhR's ability to target transporters within the kidney is essentially unexplored. We show here that exposing isolated killifish (Fundulus heteroclitus) renal proximal tubules to micromolar β-naphthoflavone (BNF) or nanomolar TCDD roughly doubled the transport activity of Multidrug resistance-associated proteins Mrp2 and Mrp4, P-glycoprotein (P-gp) and Breast cancer resistance protein (Bcrp), all ATP-driven xenobiotic efflux pumps and critical determinants of renal xenobiotic excretion. Read More

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http://dx.doi.org/10.1515/hsz-2018-0425DOI Listing
April 2019
2 Reads

Nanomedical detection and downstream analysis of circulating tumor cells in head and neck patients.

Biol Chem 2019 Apr 22. Epub 2019 Apr 22.

Nanobiomedicine Department/Department of Otorhinolaryngology-Head and Neck Surgery/ENT, University Medical Center Mainz, Langenbeckstrasse 1, D-55131 Mainz, Germany.

The establishment of novel biomarkers in liquid biopsies of cancer patients has come more into focus in prognostic and diagnostic research efforts. Due to their prognostic relevance disseminated tumor cells or circulating tumor cells are the subject of intensive research and are discussed as early diagnostic indicators for treatment failure and the formation of micrometastases. A potential association of this early-systemic tumor component with poor prognosis of cancer patients could be already demonstrated for various entities including breast, colon, lung, melanoma, ovarian and prostate cancers. Read More

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http://dx.doi.org/10.1515/hsz-2019-0141DOI Listing
April 2019
1 Read

Quinoxalinedione deprotonation is important for glutamate receptor binding.

Biol Chem 2019 Apr 22. Epub 2019 Apr 22.

Department of Biology and Biotechnology, Ruhr University Bochum, Universitätsstrasse 150, D-44801 Bochum, Germany.

Quinoxalinediones are an important class of competitive antagonists at ionotropic glutamate receptors (iGluRs), where they are widely used to block α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptor responses. In this study we utilize two prototypic quinoxalinedione antagonists, namely DNQX and CNQX, which quench the intrinsic fluorescence of the ligand binding domain (LBD), to perform in vitro binding assays. We find that binding of DNQX and CNQX at the AMPA receptor GluA2 LBD is strongly pH dependent, whereas glutamate binding is not affected by pH. Read More

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http://dx.doi.org/10.1515/hsz-2018-0464DOI Listing

LncRNA DYNLRB2-2 inhibits THP-1 macrophage foam cell formation by enhancing autophagy.

Biol Chem 2018 Dec 1. Epub 2018 Dec 1.

Department of Cardiology, Henan Provincial People's Hospital, Fuwai Central China Cardiovascular Hospital, School of Clinical Medicine, Henan University, No. 7 Weiwu Road, Zhengzhou 450003, Henan, China.

The aim of this study was to investigate whether LncRNA DYNLRB2-2 can inhibite foam cell formation by activating autophagy. The location of DYNLRB2-2 in THP-1-derived macrophages was analyzed by fluorescence in situ hybridization. ox-LDL was used to induce the formation of foam cells, Oil Red O staining and HPLC were performed to detect accumulation of lipid dropletsand the level of cholesterol concentration, respectively. Read More

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http://dx.doi.org/10.1515/hsz-2018-0461DOI Listing
December 2018

Geniposide alleviates lipopolysaccharide (LPS)-induced inflammation by downregulation of miR-27a in rat pancreatic acinar cell AR42J.

Biol Chem 2019 Apr 13. Epub 2019 Apr 13.

Department of Critical Care Medicine, Jining No. 1 People's Hospital, No. 6 Jiankang Road, Jining 272000, China.

Pancreatitis is a disease caused by inflammation of pancreatic acinar cells. Geniposide (GEN) possesses anti-inflammation activities. Hence, we investigated the effects of GEN on lipopolysaccharide (LPS)-stimulated AR42J cells. Read More

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http://dx.doi.org/10.1515/hsz-2018-0422DOI Listing

The Gid-complex: an emerging player in the ubiquitin ligase league.

Biol Chem 2019 Mar 20. Epub 2019 Mar 20.

Martin Luther University Halle-Wittenberg, Institute of Physiological Chemistry, Hollystr. 1, D-06114 Halle, Germany.

The Saccharomyces cerevisiae Gid-complex is a highly evolutionary conserved ubiquitin ligase with at least seven protein subunits. Here, we review our knowledge about the yeast Gid-complex as an important regulator of glucose metabolism, specifically targeting key enzymes of gluconeogenesis for degradation. Furthermore, we summarize existing data about the individual subunits, the topology and possible substrate recognition mechanisms and compare the striking similarities, but also differences, between the yeast complex and its vertebrate counterpart. Read More

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http://dx.doi.org/10.1515/hsz-2019-0139DOI Listing
March 2019
1 Read

Benefits of stable isotope labeling in RNA analysis.

Biol Chem 2019 Apr 8. Epub 2019 Apr 8.

Department of Chemistry, Ludwig-Maximilians-University Munich, Butenandtstr. 5-13, D-81377 Munich, Germany.

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. Read More

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http://dx.doi.org/10.1515/hsz-2018-0447DOI Listing

The effects of oxidative stress on the development of atherosclerosis.

Biol Chem 2019 Apr 9. Epub 2019 Apr 9.

Microbial Biotechnology Research Center, Biochemistry Department, Firoozabadi Hospital, Iran University of Medical Sciences, Tehran, Iran.

Atherosclerosis is a cardiovascular disease (CVD) known widely world wide. 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 the most investigated. Read More

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http://www.degruyter.com/view/j/bchm.just-accepted/hsz-2018-
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http://dx.doi.org/10.1515/hsz-2018-0397DOI Listing
April 2019
4 Reads

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 1. Epub 2018 Dec 1.

Department of Medical Genetics and Applied Genomics, University of Tübingen, Calwerstr. 7, D-72076 Tübingen, Germany.

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 substrates in vivo. Read More

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http://dx.doi.org/10.1515/hsz-2018-0438DOI Listing
December 2018

Complexity of type IV collagens: from network assembly to function.

Biol Chem 2019 Apr;400(5):565-574

State Key Laboratory of Cell Biology, CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, People's Republic of China.

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. Read More

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http://dx.doi.org/10.1515/hsz-2018-0317DOI Listing
April 2019
1 Read

Mitochondria, Apoptosis and Cancer (MAC) 2017.

Authors:
Boris Turk

Biol Chem 2019 Jan 11. Epub 2019 Jan 11.

J. Stefan Institute, Department of Biochemistry and Molecular and Structural Biology, SI-1000 Ljubljana, Slovenia.

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http://dx.doi.org/10.1515/hsz-2018-0462DOI Listing
January 2019

Characterization and engineering of photoactivated adenylyl cyclases.

Biol Chem 2019 Jan 9. Epub 2019 Jan 9.

Lehrstuhl für Biochemie, Universität Bayreuth, D-95447 Bayreuth, Germany.

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. Read More

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http://dx.doi.org/10.1515/hsz-2018-0375DOI Listing
January 2019

Sequence selection by FitSS4ASR alleviates ancestral sequence reconstruction as exemplified for geranylgeranylglyceryl phosphate synthase.

Biol Chem 2019 Jan 9. Epub 2019 Jan 9.

Institute of Biophysics and Physical Biochemistry, University of Regensburg, Universitätsstraße 31, D-93040 Regensburg, Germany.

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. Read More

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http://dx.doi.org/10.1515/hsz-2018-0344DOI Listing
January 2019
1 Read

Highly flexible, IgG-shaped, trivalent antibodies effectively target tumor cells and induce T cell-mediated killing.

Biol Chem 2019 Jan 9. Epub 2019 Jan 9.

Roche Pharma Research and Early Development, Large Molecule Research, Roche Innovation Center Munich, Nonnenwald 2, D-82377 Penzberg, Germany.

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. Read More

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http://dx.doi.org/10.1515/hsz-2018-0338DOI Listing
January 2019

Indigoid dyes by group E monooxygenases: mechanism and biocatalysis.

Biol Chem 2019 Mar 20. Epub 2019 Mar 20.

Institute of Biosciences, Environmental Microbiology, TU Bergakademie Freiberg, Leipziger Str. 29, D-09599 Freiberg, Germany.

Since ancient times, people have been attracted by dyes and they were a symbol of power. Some of the oldest dyes are indigo and its derivative Tyrian purple, which were extracted from plants and snails, respectively. These 'indigoid dyes' were and still are used for coloration of textiles and as a food additive. Read More

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http://www.degruyter.com/view/j/bchm.just-accepted/hsz-2019-
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http://dx.doi.org/10.1515/hsz-2019-0109DOI Listing
March 2019
8 Reads

Transient receptor potential channels in the context of nociception and pain - recent insights into TRPM3 properties and function.

Authors:
Marc Behrendt

Biol Chem 2019 Mar 23. Epub 2019 Mar 23.

Experimental Pain Research, Heidelberg University, Medical Faculty Mannheim, CBTM, Tridomus, Building C, Ludolf-Krehl-Straße 13-17, D-68167 Mannheim, Germany.

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. Read More

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http://dx.doi.org/10.1515/hsz-2018-0455DOI Listing

Long non-coding RNA CHRF promotes proliferation and mesenchymal transition (EMT) in prostate cancer cell line PC3 requiring up-regulating microRNA-10b.

Biol Chem 2018 Dec 1. Epub 2018 Dec 1.

School of Pharmacy (School of Enology), Binzhou Medical University, No. 346 Guanhai Road, Yantai264003,China.

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. Read More

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http://dx.doi.org/10.1515/hsz-2018-0380DOI Listing
December 2018
2 Reads

Regulation and related mechanism of GSN mRNA level by hnRNPK in lung adenocarcinoma cells.

Biol Chem 2019 Mar 8. Epub 2019 Mar 8.

Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China.

Gelsolin (GSN) is an actin filament-capping protein that plays a key role in cell migration. Here we show 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 a positive role of hnRNPK in the regulation of GSN expression. Read More

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http://dx.doi.org/10.1515/hsz-2018-0417DOI Listing
March 2019
2 Reads

Nm23-H1 inhibits hypoxia induced epithelial-mesenchymal transition and stemness in non-small cell lung cancer cells.

Biol Chem 2019 Feb 14. Epub 2019 Feb 14.

Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu, China.

The Nm23 gene has been acknowledged to play a crucial role in lung cancer metastasis inhibitory cascades controlled by multiple factors. Low expression or allelic deletion of nm23-H1 is strongly linked to widespread metastasis and poor differentiation of non-small cell lung cancer (NSCLC). 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. Read More

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http://dx.doi.org/10.1515/hsz-2018-0351DOI Listing
February 2019
1 Read

Characterization and engineering of photoactivated adenylyl cyclases.

Biol Chem 2019 Feb;400(3):429-441

Lehrstuhl für Biochemie, Universität Bayreuth, D-95447 Bayreuth, Germany.

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. Read More

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http://dx.doi.org/10.1515/hsz-2018-0375DOI Listing
February 2019

Sequence selection by FitSS4ASR alleviates ancestral sequence reconstruction as exemplified for geranylgeranylglyceryl phosphate synthase.

Biol Chem 2019 Feb;400(3):367-381

Institute of Biophysics and Physical Biochemistry, University of Regensburg, Universitätsstraße 31, D-93040 Regensburg, Germany.

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. Read More

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http://dx.doi.org/10.1515/hsz-2018-0344DOI Listing
February 2019

Highly flexible, IgG-shaped, trivalent antibodies effectively target tumor cells and induce T cell-mediated killing.

Biol Chem 2019 Feb;400(3):343-350

Roche Pharma Research and Early Development, Large Molecule Research, Roche Innovation Center Munich, Nonnenwald 2, D-82377 Penzberg, Germany.

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. Read More

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http://dx.doi.org/10.1515/hsz-2018-0338DOI Listing
February 2019
2 Reads

CFTR structure, stability, function and regulation.

Biol Chem 2019 Feb 23. Epub 2019 Feb 23.

School of Biological Sciences, Faculty of Biology Medicine and Health, Michael Smith Building, The University of Manchester, Oxford Road, Manchester M13 9PL, UK.

Cystic fibrosis transmembrane conductance regulator (CFTR) 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 origin. 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 three-dimensional (3D) folded state. Read More

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http://dx.doi.org/10.1515/hsz-2018-0470DOI Listing
February 2019
4 Reads

LncRNA HOTAIR targets miR-126-5p to promote the progression of Parkinson's disease through RAB3IP.

Biol Chem 2018 Dec 1. Epub 2018 Dec 1.

Department of Organic Chemistry, College of Chemistry, Jilin University, No. 2699 Qianjin Street, Changchun 130012, Jilin, China.

Parkinson's disease (PD) is a common neurological disorder characterized by dopaminergic (DA) neuron degeneration and death in the midbrain, and the long noncoding RNA HOTAIR has been shown to affect disease progression in PD. 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. Read More

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http://dx.doi.org/10.1515/hsz-2018-0431DOI Listing
December 2018
1 Read

Metalloprotease inhibitor profiles of human ADAM8 in vitro and in cell-based assays.

Biol Chem 2019 Mar 4. Epub 2019 Mar 4.

Department of Neurosurgery, University of Marburg, Baldingerstrasse, D-35033 Marburg, Germany.

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. Read More

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http://www.degruyter.com/view/j/bchm.ahead-of-print/hsz-2018
Publisher Site
http://dx.doi.org/10.1515/hsz-2018-0396DOI Listing
March 2019
1 Read

Zinc-induced activation of GPR39 regulates glucose homeostasis through glucose-dependent insulinotropic polypeptide secretion from enteroendocrine K-cells.

Biol Chem 2018 Dec 1. Epub 2018 Dec 1.

School of Biomedical Sciences, Ulster University, Cromore Road, ColeraineBT52 1SA, NorthernIreland.

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<0. Read More

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http://dx.doi.org/10.1515/hsz-2018-0393DOI Listing
December 2018
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Molecular effects of dietary fatty acids on brain insulin action and mitochondrial function.

Biol Chem 2019 Feb 28. Epub 2019 Feb 28.

Central Regulation of Metabolism, German Institute of Human Nutrition (DIfE), Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal, Germany.

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 (FAs) and affects adaptive metabolic response, which is connected to mitochondrial function and insulin signaling. This review will address the effect of dietary FAs on brain insulin and mitochondrial function with a special emphasis on the impact of different FAs on brain function and metabolism. Read More

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http://dx.doi.org/10.1515/hsz-2018-0477DOI Listing
February 2019

ABCB4/MDR3 in health and disease - at the crossroads of biochemistry and medicine.

Biol Chem 2019 Mar 27. Epub 2019 Mar 27.

Institute of Biochemistry, Heinrich Heine University Düsseldorf, Universitätsstraße 1, D-40225 Düsseldorf, Germany.

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 (PC) lipids from the inner to the outer leaflet of the canalicular membrane of hepatocytes. Read More

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http://dx.doi.org/10.1515/hsz-2018-0441DOI Listing
March 2019
2 Reads

Protein engineering comes of age.

Authors:
Harald Kolmar

Biol Chem 2019 Feb;400(3):255-256

Applied Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Str.-4, D-64287 Darmstadt, Germany.

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http://dx.doi.org/10.1515/hsz-2019-0108DOI Listing
February 2019

MCT1, MCT4 and CD147 expression and 3-bromopyruvate toxicity in colorectal cancer cells are modulated by the extracellular conditions.

Biol Chem 2019 Feb 14. Epub 2019 Feb 14.

CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra, 1317, 4585-116, Gandra, PRD, Portugal.

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 anti-tumor agent, whose uptake occurs via MCTs. It was the aim of this work to unravel the importance of extracellular conditions on the regulation of MCTs and in 3BP activity. Read More

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http://dx.doi.org/10.1515/hsz-2018-0411DOI Listing
February 2019

Nodal promotes the malignancy of non-small cell lung cancer (NSCLC) cells via activation of NF-κB/IL-6 signals.

Biol Chem 2019 Mar 23. Epub 2019 Mar 23.

Department of Thoracic Surgery, Peking Union Medical College Hospital, Shuaifuyuan No. 1, Dongcheng District, Beijing 100730, China.

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 cells is important for therapy and drug development. Nodal, an important embryonic morphogen, has been reported to modulate tumorigenesis. Read More

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http://dx.doi.org/10.1515/hsz-2018-0392DOI Listing

Computational design of structured loops for new protein functions.

Biol Chem 2019 Feb;400(3):275-288

Graduate Group in Biophysics, University of California San Francisco, San Francisco, CA 94158, USA.

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. Read More

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http://dx.doi.org/10.1515/hsz-2018-0348DOI Listing
February 2019

Hit evaluation of an α-helical peptide: Ala-scan, truncation and sidechain-to-sidechain macrocyclization of an RNA polymerase Inhibitor.

Biol Chem 2019 Feb;400(3):333-342

Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), Department of Drug Design and Optimization, Campus E8.1, D-66123 Saarbrücken, Germany.

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 a novel mode of action. In this work, we investigated the impact of several systematic modifications including sidechain-to-sidechain macrocylization in the α-helical content and biological activity of a previously identified inhibitory sigma factor fragment. Read More

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http://dx.doi.org/10.1515/hsz-2018-0333DOI Listing
February 2019
2 Reads

Organic anion transporters 1 and 3 influence cellular energy metabolism in renal proximal tubule cells.

Biol Chem 2019 Jan 29. Epub 2019 Jan 29.

Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, NL-6500HB, Nijmegen, The Netherlands.

Organic anion transporters (OATs) 1 and 3 are, besides being uptake transporters, key in several cellular metabolic pathways. The underlying mechanisms are largely unknown. Hence, we used human conditionally immortalized proximal tubule epithelial cells (ciPTEC) overexpressing OAT1 or OAT3 to gain insight into these mechanisms. Read More

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http://dx.doi.org/10.1515/hsz-2018-0446DOI Listing
January 2019
6 Reads

The conserved theme of ribosome hibernation: from bacteria to chloroplasts of plants.

Biol Chem 2019 Feb 1. Epub 2019 Feb 1.

Department of Biology, Molecular Genetics of Eukaryotes, University of Kaiserslautern, Paul-Ehrlich-Straße 23, D-67663 Kaiserslautern, Germany.

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, remodeling of metabolic pathways and morphological changes of the cell shape. Nutrient starvation can lead to limited energy supply and consequently, remodeling of protein synthesis is one of the key steps of regulation since the translation of the genetic code into functional polypeptides may consume up to 40% of a cell's energy during proliferation. Read More

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http://dx.doi.org/10.1515/hsz-2018-0436DOI Listing
February 2019
25 Reads

Chemical modification of neuropeptide Y for human Y1 receptor targeting in health and disease.

Biol Chem 2019 Feb;400(3):299-311

Institute of Biochemistry, Faculty of Life Sciences, Leipzig University, Brüderstr. 34, D-04103 Leipzig, Germany.

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 well as in obesity, mood disorders and cancer. Read More

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http://dx.doi.org/10.1515/hsz-2018-0364DOI Listing
February 2019
6 Reads

Changqin NO. 1 inhibits neuronal apoptosis via suppressing GAS5 expression in traumatic brain injury mice model.

Biol Chem 2018 Dec 1. Epub 2018 Dec 1.

Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410078, Hunan, China.

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. Read More

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http://dx.doi.org/10.1515/hsz-2018-0340DOI Listing
December 2018
11 Reads

Kinetically selective and potent inhibitors of HDAC8.

Biol Chem 2018 Dec 1. Epub 2018 Dec 1.

Department of Chemical Engineering and Biotechnology, University of Applied Sciences Darmstadt, 64295 Darmstadt, Germany.

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. Read More

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http://dx.doi.org/10.1515/hsz-2018-0363DOI Listing
December 2018
7 Reads

Directed evolution of the 3C protease from coxsackievirus using a novel fluorescence-assisted intracellular method.

Biol Chem 2019 Feb;400(3):405-415

Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, SE-106 91 Stockholm, Sweden.

Proteases are crucial for regulating biological processes in organisms through hydrolysis of peptide bonds. Recombinant proteases have moreover become important tools in biotechnological, and biomedical research and as therapeutics. We have developed a label-free high-throughput method for quantitative assessment of proteolytic activity in Escherichia coli. Read More

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http://dx.doi.org/10.1515/hsz-2018-0362DOI Listing
February 2019
21 Reads