55,701 results match your criteria Biochemical Journal[Journal]


Structure-based enzyme engineering improves donor-substrate recognition of Arabidopsis thaliana Glycosyltransferases.

Biochem J 2020 Jul 13. Epub 2020 Jul 13.

University College London, London, United Kingdom.

Glycosylation of secondary metabolites involves plant UDP-dependent glycosyltransferases (UGTs). UGTs have shown promise as catalysts in the synthesis of glycosides for medical treatment. However, limited understanding at the molecular level due to insufficient biochemical and structural information has hindered potential applications of most of these UGTs. Read More

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http://dx.doi.org/10.1042/BCJ20200477DOI Listing

Identification and characterization of adipose surface epitopes.

Biochem J 2020 Jul;477(13):2509-2541

RG Adipocytes and Metabolism, Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany.

Adipose tissue is a central regulator of metabolism and an important pharmacological target to treat the metabolic consequences of obesity, such as insulin resistance and dyslipidemia. Among the various cellular compartments, the adipocyte cell surface is especially appealing as a drug target as it contains various proteins that when activated or inhibited promote adipocyte health, change its endocrine function and eventually maintain or restore whole-body insulin sensitivity. In addition, cell surface proteins are readily accessible by various drug classes. Read More

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http://dx.doi.org/10.1042/BCJ20190462DOI Listing

The autocrine role of FGF21 in cultured adipocytes.

Biochem J 2020 Jul;477(13):2477-2487

Global Drug Discovery, Novo Nordisk A/S, Måløv, Denmark.

Exposure to cold alters glucose and lipid metabolism of white and brown adipose tissue via activation of β-adrenergic receptor (ADRB). Fibroblast growth factor 21 (FGF21) has been shown to be locally released from adipose tissue upon activation of ADRBs and FGF21 increases glucose uptake in adipocytes. Therefore, FGF21 may play an autocrine role in inducing glucose uptake after β-adrenergic stimulation. Read More

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http://dx.doi.org/10.1042/BCJ20200220DOI Listing

MAPK-interacting kinase 2 (MNK2) regulates adipocyte metabolism independently of its catalytic activity.

Biochem J 2020 Jul 10. Epub 2020 Jul 10.

South Australian Health & Medical Research Insitute, Adelaide, Australia.

The mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are serine/threonine protein kinases that are activated by the ERK1/2 (extracellular-regulated kinase) and p38α/β MAPK pathways. The MNKs have previously been implicated in metabolic disease and shown to mediate diet-induced obesity. In particular, knockout of MNK2 in mice protects from the weight gain induced by a high-fat diet. Read More

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http://dx.doi.org/10.1042/BCJ20200433DOI Listing

Enantioseparation, in vitro testing, and structural characterization of triple-binding reactivators of organophosphate-inhibited cholinesterases.

Biochem J 2020 Jul 8. Epub 2020 Jul 8.

Institute for Medical Research and Occupational Health, Zagreb, Croatia.

The enantiomers of racemic 2-hydroxyimino-N-(azidophenylpropyl)acetamide-derived triple-binding oxime reactivators were separated, and tested for inhibition and reactivation of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibited with tabun (GA), cyclosarin (GF), sarin (GB), and VX. Both enzymes showed the greatest affinity toward the methylimidazole derivative (III) of 2-hydroxyimino-N-(azidophenylpropyl)acetamide (I). The crystal structure was determined for the complex of oxime III within human BChE, confirming that all three binding groups interacted with active site residues. Read More

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http://dx.doi.org/10.1042/BCJ20200192DOI Listing

Merkel Cell Polyomavirus Small Tumour Antigen Activates the p38 MAPK Pathway to Enhance Cellular Motility.

Biochem J 2020 Jul 8. Epub 2020 Jul 8.

University of Leeds, Leeds, United Kingdom.

Merkel cell carcinoma (MCC) is an aggressive skin cancer with high rates of recurrence and metastasis. Merkel cell polyomavirus (MCPyV) is associated with the majority of MCC cases. MCPyV-induced tumourigenesis is largely dependent on the expression of the small tumour antigen (ST). Read More

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http://dx.doi.org/10.1042/BCJ20200399DOI Listing

Dissecting capture and twisting of aureolysin and pseudolysin: functional amino acids of the Dispase autolysis-inducing protein.

Biochem J 2020 Jun 30. Epub 2020 Jun 30.

Hochschule Darmstadt, Darmstadt, Germany.

The Dispase autolysis-inducing protein (DAIP) from Streptomyces mobaraensis attracts M4 metalloproteases, which results in inhibition and autolysis of bacillolysin (BL) and thermolysin (TL). The present study shows that aureolysin (AL) from Staphylococcus aureus and pseudolysin (LasB) from Pseudomonas aeruginosa are likewise impaired by DAIP. Complete inhibition occurred when DAIP significantly exceeded the amount of the target protease. Read More

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http://dx.doi.org/10.1042/BCJ20200407DOI Listing

Cr(VI)-induced overactive mitophagy contributes to mitochondrial loss and cytotoxicity in L02 hepatocytes.

Biochem J 2020 Jun 29. Epub 2020 Jun 29.

Xiangya School of Public Health, Central South University, Changsha, China.

Hexavalent chromium [Cr(VI)] has aroused the main interest of environmental health researchers due to its high toxicity. Liver is the main target organ of Cr(VI), and the purpose of this study was to explore whether mitophagy contributes to Cr(VI)-induced hepatotoxicity and to demonstrate the potential mechanisms. Cr(VI) exposure induced mitochondrial loss, energy metabolism disorders and cell apoptosis, which were associated with the occurrence of excessive mitophagy characterized by the increased number of green fluorescent protein-microtubule-associated protein light chain 3 (GFP-LC3) puncta and lysosomal colocalization with mitochondria. Read More

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http://dx.doi.org/10.1042/BCJ20200262DOI Listing

Molecular mechanism of Fast Endophilin-Mediated Endocytosis.

Biochem J 2020 Jun;477(12):2327-2345

Institute of Structural and Molecular Biology, University College London, Gower Street, London WC1E 6BT, U.K.

Endocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Clathrin-mediated endocytosis (CME) is the housekeeping pathway in resting cells but additional Clathrin-independent endocytic (CIE) routes, including Fast Endophilin-Mediated Endocytosis (FEME), internalize specific cargoes and support diverse cellular functions. FEME is part of the Dynamin-dependent subgroup of CIE pathways. Read More

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http://dx.doi.org/10.1042/BCJ20190342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319585PMC

Cytoskeleton regulators CAPZA2 and INF2 associate with CFTR to control its plasma membrane levels under EPAC1 activation.

Biochem J 2020 Jul;477(13):2561-2580

Faculty of Sciences, BioISI-Biosystems and Integrative Sciences Institute, University of Lisboa, Campo Grande, 1749-016 Lisboa, Portugal.

Cystic Fibrosis (CF), the most common lethal autosomic recessive disorder among Caucasians, is caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein, a cAMP-regulated chloride channel expressed at the apical surface of epithelial cells. Cyclic AMP regulates both CFTR channel gating through a protein kinase A (PKA)-dependent process and plasma membane (PM) stability through activation of the exchange protein directly activated by cAMP1 (EPAC1). This cAMP effector, when activated promotes the NHERF1:CFTR interaction leading to an increase in CFTR at the PM by decreasing its endocytosis. Read More

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http://dx.doi.org/10.1042/BCJ20200287DOI Listing

The origin, evolution and diversification of multiple isoforms of light-dependent protochlorophyllide oxidoreductase (LPOR): focus on angiosperms.

Biochem J 2020 Jun;477(12):2221-2236

Department of Plant Physiology and Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland.

Light-dependent protochlorophyllide oxidoreductase (LPOR) catalyzes the reduction of protochlorophyllide to chlorophyllide, which is a key reaction for angiosperm development. Dark operative light-independent protochlorophyllide oxidoreductase (DPOR) is the other enzyme able to catalyze this reaction, however, it is not present in angiosperms. LPOR, which evolved later than DPOR, requires light to trigger the reaction. Read More

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http://dx.doi.org/10.1042/BCJ20200323DOI Listing

High light induces species specific changes in the membrane lipid composition of Chlorella.

Biochem J 2020 Jul;477(13):2543-2559

Institute of Bio- and Geosciences (IBG-2: Plant Sciences), Forschungszentrum Jülich, 52425 Jülich, Germany.

Algae have evolved several mechanisms to adjust to changing environmental conditions. To separate from their surroundings, algal cell membranes form a hydrophobic barrier that is critical for life. Thus, it is important to maintain or adjust the physical and biochemical properties of cell membranes which are exposed to environmental factors. Read More

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http://dx.doi.org/10.1042/BCJ20200160DOI Listing

Thermogenic adipocytes: lineage, function and therapeutic potential.

Biochem J 2020 Jun;477(11):2071-2093

MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital, London W12 0NN, U.K.

Metabolic inflexibility, defined as the inability to respond or adapt to metabolic demand, is now recognised as a driving factor behind many pathologies associated with obesity and the metabolic syndrome. Adipose tissue plays a pivotal role in the ability of an organism to sense, adapt to and counteract environmental changes. It provides a buffer in times of nutrient excess, a fuel reserve during starvation and the ability to resist cold-stress through non-shivering thermogenesis. Read More

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http://dx.doi.org/10.1042/BCJ20200298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293110PMC

Molecular architecture of the acetohydroxyacid synthase holoenzyme.

Biochem J 2020 Jul;477(13):2439-2449

State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Weijin 94, Tianjin 300071, China.

The acetohydroxyacid synthase (AHAS) holoenzyme catalyzes the first step of branch-chain amino acid biosynthesis and is essential for plants and bacteria. It consists of a regulatory subunit (RSU) and a catalytic subunit (CSU). The allosteric mechanism of the AHAS holoenzyme has remained elusive for decades. Read More

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http://dx.doi.org/10.1042/BCJ20200292DOI Listing
July 2020
4.396 Impact Factor

Selective inhibition of Rhizopus eumelanin biosynthesis by novel natural product scaffold-based designs caused significant inhibition of fungal pathogenesis.

Biochem J 2020 Jul;477(13):2489-2507

Division of Infectious Diseases, The Lundquist Institute for Biomedical Innovations, Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, CA 90509, U.S.A.

Melanin is a dark color pigment biosynthesized naturally in most living organisms. Fungal melanin is a major putative virulence factor of Mucorales fungi that allows intracellular persistence by inducing phagosome maturation arrest. Recently, it has been shown that the black pigments of Rhizopus delemar is of eumelanin type, that requires the involvement of tyrosinase (a copper-dependent enzyme) in its biosynthesis. Read More

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http://dx.doi.org/10.1042/BCJ20200310DOI Listing
July 2020
4.396 Impact Factor

Antitoxin autoregulation of M. tuberculosis toxin-antitoxin expression through negative cooperativity arising from multiple inverted repeat sequences.

Biochem J 2020 Jun;477(12):2401-2419

Department of Biosciences, Durham University, Stockton Road, Durham DH1 3LE, U.K.

Toxin-antitoxin systems play key roles in bacterial adaptation, including protection from antibiotic assault and infection by bacteriophages. The type IV toxin-antitoxin system AbiE encodes a DUF1814 nucleotidyltransferase-like toxin, and a two-domain antitoxin. In Streptococcus agalactiae, the antitoxin AbiEi negatively autoregulates abiE expression through positively co-operative binding to inverted repeats within the promoter. Read More

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http://dx.doi.org/10.1042/BCJ20200368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319586PMC

The SGLT2 inhibitor canagliflozin suppresses lipid synthesis and interleukin-1 beta in ApoE deficient mice.

Biochem J 2020 Jun;477(12):2347-2361

Department of Medicine, Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada.

Sodium-glucose cotransporter 2 inhibitors such as canagliflozin lower blood glucose and reduce cardiovascular events in people with type 2 diabetes through mechanisms that are not fully understood. Canagliflozin has been shown to increase the activity of the AMP-activated protein kinase (AMPK), a metabolic energy sensor important for increasing fatty acid oxidation and energy expenditure and suppressing lipogenesis and inflammation, but whether AMPK activation is important for mediating some of the beneficial metabolic effects of canagliflozin has not been determined. We, therefore, evaluated the effects of canagliflozin in female ApoE-/- and ApoE-/-AMPK β1-/- mice fed a western diet. Read More

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http://dx.doi.org/10.1042/BCJ20200278DOI Listing

DhHP-6 ameliorates hepatic oxidative stress and insulin resistance in type 2 diabetes mellitus through the PI3K/AKT and AMPK pathway.

Biochem J 2020 Jun;477(12):2363-2381

School of Life Sciences, Jilin University, Changchun 130012, China.

Insulin resistance is one major features of type 2 diabetes mellitus (T2DM). Deuterohemin-βAla-His-Thr-Val-Glu-Lys (DhHP-6), a novel microperoxidase mimetic designed and synthesized based on microperoxidase 11 (MP-11), can scavenge reactive oxygen species (ROS) in vivo. In our previous studies, we showed that oral DhHP-6 could reduce blood glucose and improve insulin resistance. Read More

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http://dx.doi.org/10.1042/BCJ20200402DOI Listing

Use of the Polo-like kinase 4 (PLK4) inhibitor centrinone to investigate intracellular signalling networks using SILAC-based phosphoproteomics.

Biochem J 2020 Jul;477(13):2451-2475

Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7ZB, U.K.

Polo-like kinase 4 (PLK4) is the master regulator of centriole duplication in metazoan organisms. Catalytic activity and protein turnover of PLK4 are tightly coupled in human cells, since changes in PLK4 concentration and catalysis have profound effects on centriole duplication and supernumerary centrosomes, which are associated with aneuploidy and cancer. Recently, PLK4 has been targeted with a variety of small molecule kinase inhibitors exemplified by centrinone, which rapidly induces inhibitory effects on PLK4 and leads to on-target centrosome depletion. Read More

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http://dx.doi.org/10.1042/BCJ20200309DOI Listing

Heat Shock Protein 90 Inhibitors Suppress Pyroptosis in THP-1 Cells.

Biochem J 2020 Jun 4. Epub 2020 Jun 4.

University of Missouri Kansas City, Kansas City, Missouri, United States.

Pyroptosis is a recently discovered inflammatory form of programmed cell death which is mostly triggered by infection with intracellular pathogens and critically contributes to inflammation. Mitigating pyroptosis may be a potential therapeutic target in inflammatory diseases. However, small chemicals to reduce pyroptosis is still elusive. Read More

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http://dx.doi.org/10.1042/BCJ20200351DOI Listing

Insights into the unique carboxylation reactions in the metabolism of propylene and acetone.

Biochem J 2020 Jun;477(11):2027-2038

Institute of Biological Chemistry, Washington State University, Pullman, WA 99164, U.S.A.

Alkenes and ketones are two classes of ubiquitous, toxic organic compounds in natural environments produced in several biological and anthropogenic processes. In spite of their toxicity, these compounds are utilized as primary carbon and energy sources or are generated as intermediate metabolites in the metabolism of other compounds by many diverse bacteria. The aerobic metabolism of some of the smallest and most volatile of these compounds (propylene, acetone, isopropanol) involves novel carboxylation reactions resulting in a common product acetoacetate. Read More

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http://dx.doi.org/10.1042/BCJ20200174DOI Listing

Cross-linking of bovine rhodopsin with sulfosuccinimidyl 4-(N maleimidomethyl)cyclohexane-1-carboxylate affects its functionality.

Biochem J 2020 Jun;477(12):2295-2312

Departamento de Biología Celular, División de Ciencias Biológicas, Universidad Simón Bolívar, Valle de Sartenejas, Baruta, Caracas 1081-A, Venezuela.

Rhodopsin is the photoreceptor protein involved in visual excitation in retinal rods. The functionality of bovine rhodopsin was determined following treatment with sulfosuccinimidyl 4-(N maleimidomethyl)cyclohexane-1-carboxylate (sulfo-SMCC), a bifunctional reagent capable of forming covalent cross-links between suitable placed lysines and cysteines. Denaturing polyacrylamide gel electrophoresis showed that rhodopsin incubated with sulfo-SMCC generated intermolecular dimers, trimers, and higher oligomers, although most of the sulfo-SMCC-treated protein remained as a monomer. Read More

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http://dx.doi.org/10.1042/BCJ20200376DOI Listing

Synthesis and high antiproliferative activity of dehydroabietylamine pyridine derivatives in vitro and in vivo.

Biochem J 2020 Jun;477(12):2383-2399

College of Forestry, Nanjing Forestry University, Nanjing 210037, PR China.

Several bioactive dehydroabietylamine Schiff-bases (L1-L4), amides (L5-L11) and complex CuL3(NO3)2, Cu(L5)3, Co(L6)2Cl2 had been synthesized successfully for developing more efficient but lower toxic antiproliferative compounds. Their antiproliferative activities to Hela (cervix), HepG2 (liver), MCF-7 (breast), A549 (lung) and HUVEC (umbilical vein, normal cell) were investigated in vitro. The toxicity of all compounds was less than dehydroabietylamine (L0). Read More

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http://dx.doi.org/10.1042/BCJ20200337DOI Listing

Structural and functional insights into macrophage migration inhibitory factor from Oncomelania hupensis, the intermediate host of Schistosoma japonicum.

Biochem J 2020 Jun;477(12):2133-2151

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, State-province Joint Engineering Laboratory of Targeted Drugs From Natural Products, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.

Oncomelania hupensis is the unique intermediate host of Schistosoma japonicum. As an irreplaceable prerequisite in the transmission and prevalence of schistosomiasis japonica, an in-depth study of this obligate host-parasite interaction can provide glimpse into the molecular events in the competition between schistosome infectivity and snail immune resistance. In previous studies, we identified a macrophage migration inhibitory factor (MIF) from O. Read More

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http://dx.doi.org/10.1042/BCJ20200068DOI Listing

Molecular dynamics simulations and biochemical characterization of Pf14-3-3 and PfCDPK1 interaction towards its role in growth of human malaria parasite.

Biochem J 2020 Jun;477(12):2153-2177

Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Gautam Buddha Nagar, UP 201314, India.

Scaffold proteins play pivotal role as modulators of cellular processes by operating as multipurpose conformation clamps. 14-3-3 proteins are gold-standard scaffold modules that recognize phosphoSer/Thr (pS/pT) containing conserved motifs, and confer conformational changes leading to modulation of functional parameters of their target proteins. Modulation in functional activity of kinases has been attributed to their interaction with 14-3-3 proteins. Read More

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http://dx.doi.org/10.1042/BCJ20200145DOI Listing

Novel pyrano 1,3 oxazine based ligand inhibits the epigenetic reader hBRD2 in glioblastoma.

Biochem J 2020 Jun;477(12):2263-2279

Department of Biophysics, National Institute of Mental Health and Neuro Sciences (NIMHANS), Hosur Road, Bangalore 560029, India.

Glioblastoma (GBM) is the most common primary brain malignancy, rarely amenable to treatment with a high recurrence rate. GBM are prone to develop resistance to the current repertoire of drugs, including the first-line chemotherapeutic agents with frequent recurrence, limiting therapeutic success. Recent clinical data has evidenced the BRD2 and BRD4 of the BET family proteins as the new druggable targets against GBM. Read More

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http://dx.doi.org/10.1042/BCJ20200339DOI Listing

Hsa-miR-3658 down-regulates OCT4 gene expression followed by suppressing SW480 cell proliferation and migration.

Biochem J 2020 Jun;477(12):2281-2293

Biochemistry Department, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

The pluripotency factor, OCT4 gene is a stemness marker that is involved in the tumorigenicity of different cancer types and knowing about molecular mechanisms of its regulation is crucially important. To date, a few microRNAs (miRNAs) are known to be regulators of OCT4 gene expression. Looking for the novel miRNAs which are capable of regulating OCT4 gene expression, our bioinformatics analysis introduced hsa-miR-3658 (miR-3658) as a bona fide candidate. Read More

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http://dx.doi.org/10.1042/BCJ20190619DOI Listing

A novel polyubiquitin chain linkage formed by viral Ubiquitin is resistant to host deubiquitinating enzymes.

Biochem J 2020 Jun;477(12):2193-2219

National Center for Biological Sciences, TIFR, Bangalore, India.

The Baculoviridae family of viruses encode a viral Ubiquitin (vUb) gene. Though the vUb is homologous to the host eukaryotic Ubiquitin (Ub), its preservation in the viral genome indicates unique functions that are not compensated by the host Ub. We report the structural, biophysical, and biochemical properties of the vUb from Autographa californica multiple nucleo-polyhedrosis virus (AcMNPV). Read More

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http://dx.doi.org/10.1042/BCJ20200289DOI Listing
June 2020
4.396 Impact Factor

Genome-wide identification of estrogen receptor binding sites reveals novel estrogen-responsive pathways in adult male germ cells.

Biochem J 2020 Jun;477(12):2115-2131

Department of Neuroendocrinology, ICMR-National Institute for Research in Reproductive Health (ICMR-NIRRH), Mumbai, India.

Spermatogenesis occurs in the seminiferous epithelium that shows the presence of estrogen receptors alpha (ERα) and beta (ERβ), both of which regulate gene transcription by binding to the DNA. Estrogen responsive phases of spermatogenesis are well documented; however, the genes regulated remain inexplicit. To study the regulation of genes by estrogen in male germ cells, we performed chromatin immunoprecipitation (ChIP) sequencing for ERα and ERβ under normal physiological conditions. Read More

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http://dx.doi.org/10.1042/BCJ20190946DOI Listing

The thick waxy coat of mycobacteria, a protective layer against antibiotics and the host's immune system.

Biochem J 2020 May;477(10):1983-2006

School of Biosciences, Institute of Microbiology and Infection, University of Birmingham, Edgbaston, B15 2TT Birmingham, U.K.

Tuberculosis, caused by the pathogenic bacterium Mycobacterium tuberculosis (Mtb), is the leading cause of death from an infectious disease, with a mortality rate of over a million people per year. This pathogen's remarkable resilience and infectivity is largely due to its unique waxy cell envelope, 40% of which comprises complex lipids. Therefore, an understanding of the structure and function of the cell wall lipids is of huge indirect clinical significance. Read More

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http://dx.doi.org/10.1042/BCJ20200194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261415PMC

Protochlorophyllide synthesis by recombinant cyclases from eukaryotic oxygenic phototrophs and the dependence on Ycf54.

Biochem J 2020 Jun;477(12):2313-2325

Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, U.K.

The unique isocyclic E ring of chlorophylls contributes to their role as light-absorbing pigments in photosynthesis. The formation of the E ring is catalyzed by the Mg-protoporphyrin IX monomethyl ester cyclase, and the O2-dependent cyclase in prokaryotes consists of a diiron protein AcsF, augmented in cyanobacteria by an auxiliary subunit Ycf54. Here, we establish the composition of plant and algal cyclases, by demonstrating the in vivo heterologous activity of O2-dependent cyclases from the green alga Chlamydomonas reinhardtii and the model plant Arabidopsis thaliana in the anoxygenic photosynthetic bacterium Rubrivivax gelatinosus and in the non-photosynthetic bacterium Escherichia coli. Read More

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http://dx.doi.org/10.1042/BCJ20200221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319587PMC

Regulatory thiol oxidation in chloroplast metabolism, oxidative stress response and environmental signaling in plants.

Biochem J 2020 May;477(10):1865-1878

Biochemistry and Physiology of Plants, Bielefeld University, University Str. 25, 33615 Bielefeld, Germany.

The antagonism between thiol oxidation and reduction enables efficient control of protein function and is used as central mechanism in cellular regulation. The best-studied mechanism is the dithiol-disulfide transition in the Calvin Benson Cycle in photosynthesis, including mixed disulfide formation by glutathionylation. The adjustment of the proper thiol redox state is a fundamental property of all cellular compartments. Read More

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http://dx.doi.org/10.1042/BCJ20190124DOI Listing

Structural and biochemical evidence of the glucose 6-phosphate-allosteric site of maize C4-phosphoenolpyruvate carboxylase: its importance in the overall enzyme kinetics.

Biochem J 2020 Jun;477(11):2095-2114

Departamento de Bioquímica, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510 Ciudad de México, Mexico.

Activation of phosphoenolpyruvate carboxylase (PEPC) enzymes by glucose 6-phosphate (G6P) and other phospho-sugars is of major physiological relevance. Previous kinetic, site-directed mutagenesis and crystallographic results are consistent with allosteric activation, but the existence of a G6P-allosteric site was questioned and competitive activation-in which G6P would bind to the active site eliciting the same positive homotropic effect as the substrate phosphoenolpyruvate (PEP)-was proposed. Here, we report the crystal structure of the PEPC-C4 isozyme from Zea mays with G6P well bound into the previously proposed allosteric site, unambiguously confirming its existence. Read More

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http://dx.doi.org/10.1042/BCJ20200304DOI Listing

Carrot 'antifreeze' protein has an irregular ice-binding site that confers weak freezing point depression but strong inhibition of ice recrystallization.

Biochem J 2020 Jun;477(12):2179-2192

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada K7L 3N6.

Ice-binding proteins (IBPs) are found in many biological kingdoms where they protect organisms from freezing damage as antifreeze agents or inhibitors of ice recrystallization. Here, the crystal structure of recombinant IBP from carrot (Daucus carota) has been solved to a resolution of 2.3 Å. Read More

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http://dx.doi.org/10.1042/BCJ20200238DOI Listing

AMP-activated protein kinase regulates alternative pre-mRNA splicing by phosphorylation of SRSF1.

Biochem J 2020 Jun;477(12):2237-2248

Department of Agricultural Chemistry, Faculty of Applied Biosciences, Tokyo University of Agriculture, Tokyo, Japan.

AMP-activated protein kinase (AMPK) regulates cellular energy homeostasis by inhibiting anabolic processes and activating catabolic processes. Recent studies have demonstrated that metformin, which is an AMPK activator, modifies alternative precursor mRNA (pre-mRNA) splicing. However, no direct substrate of AMPK for alternative pre-mRNA splicing has been reported. Read More

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http://dx.doi.org/10.1042/BCJ20190894DOI Listing

Methylation-mediated down-regulation of microRNA-497-195 cluster confers osteogenic differentiation in ossification of the posterior longitudinal ligament of the spine via ADORA2A.

Biochem J 2020 Jun;477(12):2249-2261

Department of Orthopaedic Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, P. R. China.

Aberrant expression of microRNAs (miRNAs) has been associated with spinal ossification of the posterior longitudinal ligament (OPLL). Our initial bioinformatic analysis identified differentially expressed ADORA2A in OPLL and its regulatory miRNAs miR-497 and miR-195. Hence, this study was conducted to clarify the functional relevance of miR-497-195 cluster in OPLL, which may implicate in Adenosine A2A (ADORA2A). Read More

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http://dx.doi.org/10.1042/BCJ20200157DOI Listing

Rationally designed peptide-based inhibitor of Aβ42 fibril formation and toxicity: a potential therapeutic strategy for Alzheimer's disease.

Biochem J 2020 Jun;477(11):2039-2054

ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Department of Chemistry, School of Physical Sciences, University of Adelaide, South Australia 5005.

Amyloid beta peptide (Aβ42) aggregation in the brain is thought to be responsible for the onset of Alzheimer's disease, an insidious condition without an effective treatment or cure. Hence, a strategy to prevent aggregation and subsequent toxicity is crucial. Bio-inspired peptide-based molecules are ideal candidates for the inhibition of Aβ42 aggregation, and are currently deemed to be a promising option for drug design. Read More

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http://dx.doi.org/10.1042/BCJ20200290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293109PMC

Starting at the beginning: endoplasmic reticulum proteostasis and systemic amyloid disease.

Biochem J 2020 May;477(9):1721-1732

Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, U.S.A.

Systemic amyloid diseases are characterized by the deposition of an amyloidogenic protein as toxic oligomers and amyloid fibrils on tissues distal from the site of protein synthesis. Traditionally, these diseases have been viewed as disorders of peripheral target tissues where aggregates are deposited, and toxicity is observed. However, recent evidence highlights an important role for endoplasmic reticulum (ER) proteostasis pathways within tissues synthesizing and secreting amyloidogenic proteins, such as the liver, in the pathogenesis of these disorders. Read More

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http://dx.doi.org/10.1042/BCJ20190312DOI Listing

Development of novel anti-malarial from structurally diverse library of molecules, targeting plant-like CDPK1, a multistage growth regulator of P. falciparum.

Biochem J 2020 May;477(10):1951-1970

Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Gautam Buddha Nagar, UP 201314, India.

Upon Plasmodium falciparum merozoites exposure to low [K+] environment in blood plasma, there is escalation of cytosolic [Ca2+] which activates Ca2+-Dependent Protein Kinase 1 (CDPK1), a signaling hub of intra-erythrocytic proliferative stages of parasite. Given its high abundance and multidimensional attributes in parasite life-cycle, this is a lucrative target for designing antimalarials. Towards this, we have virtually screened MyriaScreenII diversity collection of 10,000 drug-like molecules, which resulted in 18 compounds complementing ATP-binding pocket of CDPK1. Read More

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http://dx.doi.org/10.1042/BCJ20200045DOI Listing

Runx1 up-regulates chondrocyte to osteoblast lineage commitment and promotes bone formation by enhancing both chondrogenesis and osteogenesis.

Biochem J 2020 Jul;477(13):2421-2438

Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, U.S.A.

One of the fundamental questions in bone biology is where osteoblasts originate and how osteoblast differentiation is regulated. The mechanism underlying which factors regulate chondrocyte to osteoblast lineage commitment remains unknown. Our data showed that Runt-related transcription factor 1 (Runx1) is expressed at different stages of both chondrocyte and osteoblast differentiation. Read More

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http://dx.doi.org/10.1042/BCJ20200036DOI Listing

Translational regulation of Chk1 expression by eIF3a via interaction with the RNA-binding protein HuR.

Biochem J 2020 May;477(10):1939-1950

Department of Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, U.S.A.

eIF3a is a putative subunit of the eukaryotic translation initiation factor 3 complex. Accumulating evidence suggests that eIF3a may have a translational regulatory function by suppressing translation of a subset of mRNAs while accelerating that of other mRNAs. Albeit the suppression of mRNA translation may derive from eIF3a binding to the 5'-UTRs of target mRNAs, how eIF3a may accelerate mRNA translation remains unknown. Read More

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http://dx.doi.org/10.1042/BCJ20200025DOI Listing

A steady-state approach for inhibition of heterogeneous enzyme reactions.

Biochem J 2020 May;477(10):1971-1982

Department of Biotechnology and Biomedicine, Technical University of Denmark. Søltofts Plads, Building 224, DK-2800 Kgs. Lyngby, Denmark.

The kinetic theory of enzymes that modify insoluble substrates is still underdeveloped, despite the prevalence of this type of reaction both in vivo and industrial applications. Here, we present a steady-state kinetic approach to investigate inhibition occurring at the solid-liquid interface. We propose to conduct experiments under enzyme excess (E0 ≫ S0), i. Read More

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http://dx.doi.org/10.1042/BCJ20200083DOI Listing

Computationally designed synthetic peptides for transporter proteins imparts allostericity in Miltefosine resistant L. major.

Biochem J 2020 May;477(10):2007-2026

National Centre for Cell Science, NCCS Complex, Ganeshkhind, SP Pune University Campus, Pune 411007, India.

The emergence of drug resistance is a major concern for combating against Cutaneous Leishmaniasis, a neglected tropical disease affecting 98 countries including India. Miltefosine is the only oral drug available for the disease and Miltefosine transporter proteins play a pivotal role in the emergence of drug-resistant Leishmania major. The cause of resistance is less accumulation of drug inside the parasite either by less uptake of the drug due to a decrease in the activity of P4ATPase-CDC50 complex or by increased efflux of the drug by P-glycoprotein (P-gp, an ABC transporter). Read More

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http://dx.doi.org/10.1042/BCJ20200176DOI Listing

Synergism between SLC6A14 blockade and gemcitabine in pancreactic cancer: a 1H-NMR-based metabolomic study in pancreatic cancer cells.

Biochem J 2020 May;477(10):1923-1937

Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.

Gemcitabine is the first-line chemotherapy for pancreatic cancer. To overcome the often-acquired gemcitabine resistance, other drugs are used in combination with gemcitabine. It is well-known that cancer cells reprogram cellular metabolism, coupled with the up-regulation of selective nutrient transporters to feed into the altered metabolic pathways. Read More

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http://dx.doi.org/10.1042/BCJ20200275DOI Listing

O-glycan recognition and function in mice and human cancers.

Biochem J 2020 Apr;477(8):1541-1564

Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, CLS 11087, 3 Blackfan Circle, Boston, MA 02115, U.S.A.

Protein glycosylation represents a nearly ubiquitous post-translational modification, and altered glycosylation can result in clinically significant pathological consequences. Here we focus on O-glycosylation in tumor cells of mice and humans. O-glycans are those linked to serine and threonine (Ser/Thr) residues via N-acetylgalactosamine (GalNAc), which are oligosaccharides that occur widely in glycoproteins, such as those expressed on the surfaces and in secretions of all cell types. Read More

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http://dx.doi.org/10.1042/BCJ20180103DOI Listing

Expanding our understanding of the role polyprotein conformation plays in the coronavirus life cycle.

Biochem J 2020 04;477(8):1479-1482

Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Private Bag X6, Florida, Roodepoort 1710, South Africa.

Coronavirus are the causative agents in many globally concerning respiratory disease outbreaks such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and coronavirus disease-2019 (COVID-19). It is therefore important that we improve our understanding of how the molecular components of the virus facilitate the viral life cycle. These details will allow for the design of effective interventions. Read More

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http://dx.doi.org/10.1042/BCJ20200223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200640PMC

Effects of CGA-N12 on the membrane structure of Candida tropicalis cells.

Biochem J 2020 May;477(10):1813-1825

College of Bioengineering, Henan University of Technology, Zhengzhou, Henan 450001, P. R. China.

The antimicrobial peptide CGA-N12 (NH2-ALQGAKERAHQQ-COOH) is an active peptide derived from chromogranin A (CGA) and consists of the 65th to 76th amino acids of the N-terminus. The results of our previous studies showed that CGA-N12 exerts anti-Candida activity by inducing apoptosis without destroying the integrity of cell membranes. In this study, the effect of CGA-N12 on the cell membrane structure of Candida tropicalis was investigated. Read More

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http://dx.doi.org/10.1042/BCJ20190939DOI Listing

Small molecule H89 renders the phosphorylation of S6K1 and AKT resistant to mTOR inhibitors.

Biochem J 2020 May;477(10):1847-1863

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, U.S.A.

The mammalian target of rapamycin (mTOR) is an evolutionarily conserved Ser/Thr kinase that comprises two complexes, termed mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTORC1 phosphorylates S6K1 at Thr 389, whereas mTORC2 phosphorylates AKT at Ser 473 to promote cell growth. As the mTOR name implies it is the target of natural product called rapamycin, a clinically approved drug used to treat human disease. Read More

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http://dx.doi.org/10.1042/BCJ20190958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261416PMC

Cell Atlas technologies and insights into tissue architecture.

Biochem J 2020 Apr;477(8):1427-1442

Wellcome Sanger Institute, Cambridge, U.K.

Since Robert Hooke first described the existence of 'cells' in 1665, scientists have sought to identify and further characterise these fundamental units of life. While our understanding of cell location, morphology and function has expanded greatly; our understanding of cell types and states at the molecular level, and how these function within tissue architecture, is still limited. A greater understanding of our cells could revolutionise basic biology and medicine. Read More

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http://dx.doi.org/10.1042/BCJ20190341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200628PMC