Search Our Scientific Publications & Authors

Biochem J 2019 Feb 19. Epub 2019 Feb 19.

University of Southern Mississippi, 118 College Dr # 5043, Hattiesburg, Hattiesburg, Mississippi, 39406, United States

Granulins (GRNs 1 - 7) are cysteine-rich proteolytic products of progranulin (PGRN) that have recently been implicated in neurodegenerative diseases including frontotemporal dementia (FTD) and Alzheimer disease (AD). Their precise mechanism in these pathologies remains uncertain, but both inflammatory and lysosomal roles have been observed for GRNs. Among the seven GRNs, GRN‑3 is well-characterized and is implicated within the context of FTD. Read More

Biochem J 2019 Feb 19. Epub 2019 Feb 19.

Germany.

Autophagy is essential for cellular homeostasis and when deregulated this survival mechanism has been associated with disease development. Inhibition of autophagy initiation by inhibiting the kinase ULK1 has been proposed as a potential cancer therapy. While inhibitors and crystal structures of ULK1 have been reported, little is known about the other closely related kinase ULK2. Read More

Biochem J 2019 Feb 19. Epub 2019 Feb 19.

University of Cologne, Cologne, 50674, Germany

Seed quality is affected by different constituents of the seed. In general, seed lots are considered to be of high quality when they exhibit fast and homogeneous germination. When seeds are stored they undergo different degrees of damage that have detrimental effects on their quality. Read More

Biochem J 2019 Feb 19. Epub 2019 Feb 19.

Department of Chemistry, University of Oxford, Oxford, United Kingdom

SPH proteins are a large family of small, disulphide-bonded, secreted proteins, initially found in the self-incompatibility response in the field poppy , but now known to be widely distributed in plants, many containing multiple members of this protein family. Using the Origami strain of , we expressed one member of this family, SPH15 from , as a folded thioredoxin-fusion protein and purified it from the cytosol. The fusion protein was cleaved and characterised by analytical ultracentrifugation, circular dichroism, and NMR spectroscopy. Read More

Biochem J 2019 Feb 14;476(3):581-593. Epub 2019 Feb 14.

Department of Biotechnology, University of Verona, 37134 Verona, Italy.

LHC (light-harvesting complex) proteins of plants and algae are known to be involved both in collecting light energy for driving the primary photochemical reactions of photosynthesis and in photoprotection when the absorbed light energy exceeds the capacity of the photosynthetic apparatus. These proteins usually contain three transmembrane (TM) helices which span the thylakoid membranes and bind several chlorophyll, carotenoid and lipid molecules. In addition, the LHC protein family includes LHC-like proteins containing one, two, three or even four TM domains. Read More

Biochem J 2019 Feb 12. Epub 2019 Feb 12.

Molecular Biochemistry, Ruhr University Bochum, Universitätsstr., Bochum, 44780, Germany

Type IV P-type ATPases (P4 ATPases) are lipid flippases that catalyze phospholipid transport from the exoplasmic to the cytoplasmic leaflet of cellular membranes, but the mechanism by which they recognize and transport phospholipids through the lipid bilayer remains unknown. In this study, we succeeded in purifying recombinant Aminophospholipid ATPase 2 (ALA2), a member of the P4 ATPase subfamily in , in complex with the ALA-Interacting Subunit 5 (ALIS5). The ATP hydrolytic activity of the ALA2-ALIS5 complex was stimulated in a highly specific manner by phosphatidylserine. Read More

Biochem J 2019 Feb 7. Epub 2019 Feb 7.

Zhejiang University, Hangzhou, China

Control of organ size is a fundamental aspect in biology and plays important roles in development. The Hippo pathway is a conserved signaling cascade that controls tissue and organ size through the regulation of cell proliferation and apoptosis. Here, we report on the roles of Hcf, the homolog of Host cell factor 1, in regulating the Hippo signaling pathway. Read More

Biochem J 2019 Feb 5;476(3):433-447. Epub 2019 Feb 5.

International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India

The immune system is capable of making antibodies against anything that is foreign, yet it does not react against components of self. In that sense, a fundamental requirement of the body's immune defense is specificity. Remarkably, this ability to specifically attack foreign antigens is directed even against antigens that have not been encountered a priori by the immune system. Read More

Biochem J 2019 Feb 4. Epub 2019 Feb 4.

Tianjin University, 417-4, Bldg24, Weijin Rd, Tianjin Univ., Nankai District, Tianjin, 300072, China

Sulfoacetaldehyde reductase (IsfD) is a member of the short-chain dehydrogenase/reductase (SDR) family, involved in nitrogen assimilation from aminoethylsulfonate (taurine) in certain environmental and human commensal bacteria. IsfD catalyzes the reversible NADPH-dependent reduction of sulfoacetaladehyde, which is generated by transamination of taurine, forming hydroxyethylsulfonate (isethionate) as a waste product. In this study, the crystal structure of IsfD in a ternary complex with NADPH and isethionate, was solved at 2. Read More

Biochem J 2019 Feb 4. Epub 2019 Feb 4.

Protein Synthesis Enzymology, Institute of Molecular Biology and Genetics of the NAS of Ukraine, 150 Zabolotnogo Str., Kyiv, 03143, Ukraine.

D-aminoacyl-tRNA-deacylase (DTD) prevents the incorporation of D-amino acids into proteins during translation by hydrolyzing the ester bond between mistakenly attached amino acids and tRNAs. Despite extensive study of this proofreading enzyme, the precise catalytic mechanism remains unknown. Here, a combination of biochemical and computational investigations has enabled the discovery of a new substrate-assisted mechanism of D-Tyr-tRNA hydrolysis by DTD. Read More

Biochem J 2019 Feb 1. Epub 2019 Feb 1.

College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, College of Pharmacy, UT Austin, Austin, Texas, 78712, United States

Oxaliplatin, together with cisplatin, is among the most important drugs used in cancer chemotherapy. Oxaliplatin, which contains a bulky diaminocyclohexane (DACH) moiety, kills cancer cells mainly by producing (DACH)Pt-GpG intrastrand cross-links that impede transcription. The Pt-GpG tolerance by translesion DNA synthesis (TLS) polymerases contributes to the resistance of tumors to platinum-based chemotherapy. Read More

Biochem J 2019 Jan 31;476(2):365-374. Epub 2019 Jan 31.

UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA and Frederick National Laboratory for Cancer Research, Frederick, MD, USA

RAS proteins have traditionally been deemed undruggable, as they do not possess an active site to which small molecules could bind but small molecules that target one form of oncogenic RAS, KRAS G12C, are already in preclinical and clinical trials, and several other compounds that bind to different RAS proteins at distinct sites are in earlier stage evaluation. KRAS is the major clinical target, as it is by far the most significant form of RAS in terms of cancer incidence. Unfortunately, KRAS exists in two isoforms, each with unique biochemical properties. Read More

Biochem J 2019 Feb 19;476(4):645-663. Epub 2019 Feb 19.

Department of Biology, Faculty of Sciences, University of Guilan, 41335-19141 Rasht, Iran

Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are pivotal regulators of angiogenesis. The VEGF-VEGFR system is therefore an important target of anti-angiogenesis therapy. Based on the X-ray structure of VEGF-B/VEGFR-1 D2, we designed a cyclic peptide (known as VGB1) reproducing the α1 helix and its adjacent region to interfere with signaling through VEGFR-1. Read More

Biochem J 2019 Feb 19;476(4):683-697. Epub 2019 Feb 19.

Department of Horticultural Sciences, University of Florida, Gainesville, FL, U.S.A.

The tripeptide glutathione (GSH) is implicated in various crucial physiological processes including redox buffering and protection against heavy metal toxicity. GSH is abundant in plants, with reported intracellular concentrations typically in the 1-10 mM range. Various aminotransferases can inadvertently transaminate the amino group of the γ-glutamyl moiety of GSH to produce deaminated glutathione (dGSH), a metabolite damage product. Read More

Biochem J 2019 Feb 14;476(3):613-628. Epub 2019 Feb 14.

Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India

Proteins are dynamic in nature and exist in a set of equilibrium conformations on various timescale motions. The flexibility of proteins governs various biological functions, and therefore elucidation of such functional dynamics is essential. In this context, we have studied the structure-dynamics-stability-activity relationship of bacteriophage T7 lysozyme/endolysin (T7L) native-state ensemble in the pH range of 6-8. Read More

Biochem J 2019 Feb 19;476(4):665-682. Epub 2019 Feb 19.

Institute for Chemistry and Bioanalytics, University of Applied Sciences and Arts Northwestern Switzerland, Hofackerstrasse 30, 4132 Muttenz, Switzerland

Sortase enzymes play an important role in Gram-positive bacteria. They are responsible for the covalent attachment of proteins to the surface of the bacteria and perform this task via a highly sequence-specific transpeptidation reaction. Since these immobilized proteins are often involved in pathogenicity of Gram-positive bacteria, characterization of this type of enzyme is also of medical relevance. Read More

Biochem J 2019 Feb 19;476(4):629-643. Epub 2019 Feb 19.

De Duve Institute and WELBIO, UCLouvain, Avenue Hippocrate 75, 1200 Bruxelles, Belgium

Repair of a certain type of oxidative DNA damage leads to the release of phosphoglycolate, which is an inhibitor of triose phosphate isomerase and is predicted to indirectly inhibit phosphoglycerate mutase activity. Thus, we hypothesized that phosphoglycolate might play a role in a metabolic DNA damage response. Here, we determined how phosphoglycolate is formed in cells, elucidated its effects on cellular metabolism and tested whether DNA damage repair might release sufficient phosphoglycolate to provoke metabolic effects. Read More

Biochem J 2019 Feb 14;476(3):595-611. Epub 2019 Feb 14.

School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia 4072, Australia

Bacterial pathogens encounter a variety of adverse physiological conditions during infection, including metal starvation, metal overload and oxidative stress. Here, we demonstrate that group A (GAS) utilises Mn(II) import via MtsABC during conditions of hydrogen peroxide stress to optimally metallate the superoxide dismutase, SodA, with Mn. MtsABC expression is controlled by the DtxR family metalloregulator MtsR, which also regulates the expression of Fe uptake systems in GAS. Read More

Biochem J 2019 Feb 8;476(3):559-579. Epub 2019 Feb 8.

Laboratory of Neurodegenerative Diseases, Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece

The Parkinson's disease (PD) protein leucine-rich repeat kinase 2 (LRRK2) exists as a mixture of monomeric and dimeric species, with its kinase activity highly concentrated in the dimeric conformation of the enzyme. We have adapted the proximity biotinylation approach to study the formation and activity of LRRK2 dimers isolated from cultured cells. We find that the R1441C and I2020T mutations both enhance the rate of dimer formation, whereas, the G2019S kinase domain mutant is similar to WT, and the G2385R risk factor variant de-stabilizes dimers. Read More

Biochem J 2019 Feb 5;476(3):449-465. Epub 2019 Feb 5.

Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark

Selective autophagy has emerged as an important mechanism by which eukaryotic cells control the abundance of specific proteins. This mechanism relies on cargo recruitment to autophagosomes by receptors that bind to both the ubiquitin-like AUTOPHAGY8 (ATG8) protein through ATG8-interacting motifs (AIMs) and to the cargo to be degraded. In plants, two autophagy cargo receptors, ATG8-interacting protein 1 (ATI1) and 2 (ATI2), were identified early on, but their molecular properties remain poorly understood. Read More

Biochem J 2019 Jan 11;476(1):67-83. Epub 2019 Jan 11.

Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089-9121, U.S.A.

The use of disulfide-rich backbone-cyclized polypeptides, as molecular scaffolds to design a new generation of bioimaging tools and drugs that are potent and specific, and thus might have fewer side effects than traditional small-molecule drugs, is gaining increasing interest among the scientific and in the pharmaceutical industries. Highly constrained macrocyclic polypeptides are exceptionally more stable to chemical, thermal and biological degradation and show better biological activity when compared with their linear counterparts. Many of these relatively new scaffolds have been also found to be highly tolerant to sequence variability, aside from the conserved residues forming the disulfide bonds, able to cross cellular membranes and modulate intracellular protein-protein interactions both and These properties make them ideal tools for many biotechnological applications. Read More

Biochem J 2019 Feb 8;476(3):547-558. Epub 2019 Feb 8.

Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1L 0A5

The decline in fat oxidation at higher power outputs of exercise is a complex interaction between several mechanisms; however, the influence of mitochondrial bioenergetics in this process remains elusive. Therefore, using permeabilized muscle fibers from mouse skeletal muscle, we aimed to determine if acute exercise altered mitochondrial sensitivity to (1) adenosine diphosphate (ADP) and inorganic phosphate (Pi), or (2) carnitine palmitoyltransferase-I (CPT-I) independent (palmitoylcarnitine, PC) and dependent [palmitoyl-CoA (P-CoA), malonyl-CoA (M-CoA), and l-carnitine] substrates, in an intensity-dependent manner. As the apparent ADP increased to a similar extent following low (LI) and high (HI) intensity exercise compared with sedentary (SED) animals, and Pi sensitivity was unaltered by exercise, regulation of phosphate provision likely does not contribute to the well-established intensity-dependent shift in substrate utilization. Read More

Biochem J 2019 Feb 8;476(3):535-546. Epub 2019 Feb 8.

Department of Medicine, Duke University Medical Center, Durham, NC 27710, U.S.A.

The Wnt signaling pathway, known for regulating genes critical to normal embryonic development and tissue homeostasis, is dysregulated in many types of cancer. Previously, we identified that the anthelmintic drug niclosamide inhibited Wnt signaling by promoting internalization of Wnt receptor Frizzled 1 and degradation of Wnt signaling pathway proteins, Dishevelled 2 and β-catenin, contributing to suppression of colorectal cancer growth and Here, we provide evidence that niclosamide-mediated inhibition of Wnt signaling is mediated through autophagosomes induced by niclosamide. Specifically, niclosamide promotes the co-localization of Frizzled 1 or β-catenin with LC3, an autophagosome marker. Read More

Biochem J 2019 Feb 8;476(3):513-533. Epub 2019 Feb 8.

Department of Molecular and Cell Biology, University of Leicester, University Road, Leicester LE1 9HN, U.K.

Following nutrient ingestion, glucagon-like peptide 1 (GLP-1) is secreted from intestinal L-cells and mediates anti-diabetic effects, most notably stimulating glucose-dependent insulin release from pancreatic β-cells but also inhibiting glucagon release, promoting satiety and weight reduction and potentially enhancing or preserving β-cell mass. These effects are mediated by the GLP-1 receptor (GLP-1R), which is a therapeutic target in type 2 diabetes. Although agonism at the GLP-1R has been well studied, desensitisation and resensitisation are perhaps less well explored. Read More

Biochem J 2019 Jan 31;476(2):421-431. Epub 2019 Jan 31.

Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, P.R. China

Posttranslational modifications (PTMs) of core histones, such as histone methylation, play critical roles in a variety of biological processes including transcription regulation, chromatin condensation and DNA repair. In , no domain recognizing methylated histone has been identified so far. TbTFIIS2-2, as a potential transcription elongation factors in , contains a PWWP domain in the N-terminus which shares low sequence similarity compared with other PWWP domains and is absent from other TFIIS factors In the present study, the solution structure of TbTFIIS2-2 PWWP domain was determined by NMR spectroscopy. Read More

Biochem J 2019 Feb 5;476(3):499-512. Epub 2019 Feb 5.

Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V6T 1Z3

Cathepsin K (CatK) is a cysteine protease and drug target for skeletal disorders that is known for its potent collagenase and elastase activity. The formation of oligomeric complexes of CatK in the presence of glycosaminoglycans has been associated with its collagenase activity. Inhibitors that disrupt these complexes can selectively block the collagenase activity without interfering with the other regulatory proteolytic activities of the enzyme. Read More

Biochem J 2019 Feb 5;476(3):467-481. Epub 2019 Feb 5.

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, PR China

MOV10 has emerged as an important host antiviral factor. MOV10 not only inhibits various viruses, including human immunodeficiency virus type 1, hepatitis C virus and vesicular stomatitis virus, but also restricts the activity of retroelements long interspersed nucleotide element-1, Alu, SVA and intracisternal A particles. Here, we report that MOV10 suppresses influenza A virus infection through interacting with viral nucleoprotein (NP), sequestering viral RNP in the cytoplasm and causing the degradation of viral vRNA. Read More

Biochem J 2019 Jan 7;476(1):25-37. Epub 2019 Jan 7.

Program in Neurosciences and Mental Health, The Hospital for Sick Children, 686 Bay St, Toronto, Ontario, Canada.

The mitochondrial proteome is estimated to contain ∼1100 proteins, the vast majority of which are nuclear-encoded, with only 13 proteins encoded by the mitochondrial genome. The import of these nuclear-encoded proteins into mitochondria was widely believed to be unidirectional, but recent discoveries have revealed that many these 'mitochondrial' proteins are exported, and have extra-mitochondrial activities divergent from their mitochondrial function. Surprisingly, three of the exported proteins discovered thus far are mitochondrially encoded and have significantly different extra-mitochondrial roles than those performed within the mitochondrion. Read More

Biochem J 2019 Jan 7;476(1):1-23. Epub 2019 Jan 7.

Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195, U.S.A.

Polyphosphoinositides (PPIs) are essential phospholipids located in the cytoplasmic leaflet of eukaryotic cell membranes. Despite contributing only a small fraction to the bulk of cellular phospholipids, they make remarkable contributions to practically all aspects of a cell's life and death. They do so by recruiting cytoplasmic proteins/effectors or by interacting with cytoplasmic domains of membrane proteins at the membrane-cytoplasm interface to organize and mold organelle identity. Read More

Biochem J 2019 Feb 5;476(3):483-497. Epub 2019 Feb 5.

College of Biological Engineering, Henan University of Technology, Zhengzhou 450001, China.

CGA-N9 is a peptide derived from the N-terminus of human chromogranin A comprising amino acids 47-55. Minimum inhibitory concentration (MIC) assays showed that CGA-N9 had antimicrobial activity and exhibited time-dependent inhibition activity against , with high safety in human red blood cells (HRBCs) and mouse brain microvascular endothelial cells (bEnd.3). Read More

Biochem J 2019 Jan 31;476(2):405-419. Epub 2019 Jan 31.

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, India

Type II phosphatidylinositol 4-kinase β (PtdIns 4-kinase II β) is an enigma among the phosphatidylinositol 4-kinase family. The role of PtdIns 4-kinase II β in MCF-7 cells was addressed with the help of short hairpin RNA (shRNA). PtdIns 4-kinase II β shRNA transfection increased pan-caspase activity and induced apoptosis in cancerous MCF-7 cells. Read More

Biochem J 2019 Jan 25;476(2):293-306. Epub 2019 Jan 25.

School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, Bristol BS8 1TD, U.K.

Retromer is an evolutionarily conserved endosomal trafficking complex that mediates the retrieval of cargo proteins from a degradative pathway for sorting back to the cell surface. To promote cargo recycling, the core retromer trimer of VPS (vacuolar protein sorting)26, VPS29 and VPS35 recognises cargo either directly, or through an adaptor protein, the most well characterised of which is the PDZ [postsynaptic density 95 (PSD95), disk large, zona occludens] domain-containing sorting nexin SNX27. Neuroligins (NLGs) are postsynaptic -synaptic scaffold proteins that function in the clustering of postsynaptic proteins to maintain synaptic stability. Read More

Biochem J 2019 Jan 25;476(2):245-259. Epub 2019 Jan 25.

School of Medicine, Medical Sciences and Nutrition, Institute of Medical Science, University of Aberdeen, Aberdeen, U.K.

Glioblastoma (GB) represents the most common and aggressive form of malignant primary brain tumour associated with high rates of morbidity and mortality. In the present study, we considered the potential use of idebenone (IDE), a Coenzyme Q analogue, as a novel chemotherapeutic agent for GB. On two GB cell lines, U373MG and U87MG, IDE decreased the viable cell number and enhanced the cytotoxic effects of two known anti-proliferative agents: temozolomide and oxaliplatin. Read More

Biochem J 2018 Dec 21;475(24):4011-4023. Epub 2018 Dec 21.

Department of Cancer Biology, Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Arturo Duperier 4, E-28029 Madrid, Spain

Calmodulin (CaM) is a versatile Ca-sensor/transducer protein that modulates hundreds of enzymes, channels, transport systems, transcription factors, adaptors and other structural proteins, controlling in this manner multiple cellular functions. In addition to its capacity to regulate target proteins in a Ca-dependent and Ca-independent manner, the posttranslational phosphorylation of CaM by diverse Ser/Thr- and Tyr-protein kinases has been recognized as an important additional manner to regulate this protein by fine-tuning its functionality. In this review, we shall cover developments done in recent years in which phospho-CaM has been implicated in signalling pathways that are relevant for the onset and progression of diverse pathophysiological processes. Read More

Biochem J 2019 Jan 31;476(2):333-352. Epub 2019 Jan 31.

Department of Pharmacology, University Medical Center of the Johannes Gutenberg-University, Obere Zahlbacher Str. 67, 55101 Mainz, Germany

Type III interferons (IFNs) are the latest members of the IFN family. They play an important role in immune defense mechanisms, especially in antiviral responses at mucosal sites. Moreover, they control inflammatory reactions by modulating neutrophil and dendritic cell functions. Read More

Biochem J 2019 Jan 25;476(2):261-274. Epub 2019 Jan 25.

Section on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, U.S.A.

Gaucher disease (GD) is a rare lysosomal storage disorder caused by mutations in the gene, encoding the lysosome-resident glucocerebrosidase enzyme involved in the hydrolysis of glucosylceramide. The discovery of an association between mutations in and the development of synucleinopathies, including Parkinson disease, has directed attention to glucocerebrosidase as a potential therapeutic target for different synucleinopathies. These findings initiated an exponential growth in research and publications regarding the glucocerebrosidase enzyme. Read More

Biochem J 2018 Dec 21. Epub 2018 Dec 21.

Chemical Sciences, Tata Institute of Fundamental Research, MUMBAI, 400005, India

Antibiotic-resistant bacteria pose the greatest threat to human health. Among the list of such bacteria released by WHO, carbapenem-resistant , for which almost no treatment exists, tops the list. is one of the most troublesome ESKAPE pathogens and mechanisms that have facilitated its rise as a successful pathogen are not well studied. Read More

Biochem J 2019 Jan 25;476(2):307-332. Epub 2019 Jan 25.

Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, PO Box 5400, FI-90014 Oulu, Finland

The SCP2 (sterol carrier protein 2)-thiolase (type-1) functions in the vertebrate peroxisomal, bile acid synthesis pathway, converting 24-keto-THC-CoA and CoA into choloyl-CoA and propionyl-CoA. This conversion concerns the β-oxidation chain shortening of the steroid fatty acyl-moiety of 24-keto-THC-CoA. This class of dimeric thiolases has previously been poorly characterized. Read More

Biochem J 2019 Jan 31;476(2):375-384. Epub 2019 Jan 31.

Protein Structure-Function Research Unit, School of Molecular and Cell Biology, University of Witwatersrand, Johannesburg 2050, South Africa

HIV protease is essential for processing the Gag polyprotein to produce infectious virions and is a major target in antiretroviral therapy. We have identified an unusual HIV-1 subtype C variant that contains insertions of leucine and asparagine (L38↑N↑L) in the hinge region of protease at position 38. This was isolated from a protease inhibitor naïve infant. Read More

Biochem J 2019 Jan 31;476(2):385-404. Epub 2019 Jan 31.

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, PR China

ZNF300 plays an important role in the regulation of HBV-related hepatocellular carcinoma. However, little is known about the role of ZNF300 in lipid metabolism and NAFLD. In the present study, we observed that ZNF300 expression was markedly decreased in free fatty acid (FFA)-induced fatty liver. Read More

Biochem J 2019 Jan 11;476(1):101-113. Epub 2019 Jan 11.

Department of Biochemistry and Molecular Biology, Federal University of Ceará, Campus do Pici, Bloco 907, Fortaleza, Ceara 60451 970, Brazil.

Frutalin (FTL) is a multiple-binding lectin belonging to the jacalin-related lectin (JRL) family and derived from (breadfruit) seeds. This lectin specifically recognizes and binds α-d-galactose. FTL has been successfully used in immunobiological research for the recognition of cancer-associated oligosaccharides. Read More

Biochem J 2019 Jan 18;476(2):225-243. Epub 2019 Jan 18.

Raymond Purves Bone and Joint Research Laboratory, Kolling Institute, Northern Sydney Local Health District, St. Leonards, NSW 2065, Australia

Heparan sulfate (HS) regulates diverse cell signalling events in intervertebral disc development and homeostasis. The aim of the present study was to investigate the effect of ablation of perlecan HS/CS on murine intervertebral disc development. Genetic models carrying mutations in genes encoding HS biosynthetic enzymes have identified multiple roles for HS in tissue homeostasis. Read More

Biochem J 2019 Jan 15;476(1):151-164. Epub 2019 Jan 15.

Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada T6G 2P5

Long-chain acyl-CoA synthetase (LACS, EC 6.2.1. Read More

Biochem J 2019 Jan 25;476(2):275-292. Epub 2019 Jan 25.

Arsanis Biosciences, Campus Vienna Biocenter, Helmut-Qualtinger-Gasse 2, Vienna, Austria

Host defense against greatly depends on bacterial clearance by phagocytic cells. LukGH (or LukAB) is the most potent staphylococcal leukocidin towards human phagocytes , but its role in pathogenesis is obscured by the lack of suitable small animal models because LukGH has limited or no cytotoxicity towards rodent and rabbit compared with human polymorphonuclear cells (PMNs) likely due to an impaired interaction with its cellular receptor, CD11b. We aimed at adapting LukGH for the rabbit host by improving binding to the rabbit homolog of CD11b, specifically its I-domain (CD11b-I). Read More

Biochem J 2018 Dec 14;475(24):3921-3932. Epub 2018 Dec 14.

Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 7RH, U.K.

At face value, the Sin3 histone deacetylase (HDAC) complex appears to be a prototypical co-repressor complex, that is, a multi-protein complex recruited to chromatin by DNA bound repressor proteins to facilitate local histone deacetylation and transcriptional repression. While this is almost certainly part of its role, Sin3 stubbornly refuses to be pigeon-holed in quite this way. Genome-wide mapping studies have found that Sin3 localises predominantly to the promoters of actively transcribed genes. Read More

Biochem J 2018 Dec 14;475(24):3917-3919. Epub 2018 Dec 14.

Département de Biochimie et Médecine Moléculaire, Université de Montréal, Montréal, Canada

In a recent issue of , Kathuria et al [ (2018) , 3039-3055] report that membrane binding of the pore-forming toxin cytolysin (VCC) is facilitated by the presence of cholesterol, and the presence of this sterol within the lipid bilayer is key for the formation of a functional pore. Yet, in the presence of accessory non-lipid components, VCC retains its membrane-binding capability likely through membrane lipid raft structures. In light of their results, the authors provide new insights into the roles of cholesterol and of membrane microstructures in the binding, the oligomeric assembly and the cytolytic pore formation of VCC which all take place following infection by . Read More

Biochem J 2019 Jan 15;476(1):165-178. Epub 2019 Jan 15.

Institute for Integrative Biology of the Cell (I2BC), CNRS CEA Univ. Paris-Sud, Université Paris-Saclay, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France

pathogens genetically modify their host plants to drive the synthesis of opines in plant tumors. The mannityl-opine family encompasses mannopine, mannopinic acid, agropine and agropinic acid. These opines serve as nutrients and are imported into bacteria via periplasmic-binding proteins (PBPs) in association with ABC transporters. Read More

Biochem J 2019 Jan 15;476(1):137-149. Epub 2019 Jan 15.

Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.

Recently, we demonstrated that the anti-viral drug ribavirin (RBV) had the ability to suppress lipogenesis through down-regulation of retinoid X receptor α (RXRα) under the control of the intracellular GTP-level and AMP-activated protein kinase-related kinases, especially microtubule affinity regulating kinase 4 (MARK4). RXRα-overexpression attenuated but did not abolish lipogenesis suppression by RBV, implying that additional factor(s) were involved in this suppressive effect. In the present study, we found that the protein level, but not the mRNA level, of CCAAT/enhancer-binding protein α (C/EBPα) was down-regulated by RBV in hepatic cells. Read More

Biochem J 2018 Dec 12;475(23):3903-3915. Epub 2018 Dec 12.

Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, U.S.A.

Current problems in the understanding of colicin import across the outer membrane (OM), involving a range of cytotoxic mechanisms, are discussed: (I) Crystal structure analysis of colicin E3 (RNAase) with bound OM vitamin B receptor, BtuB, and of the N-terminal translocation (T) domain of E3 and E9 (DNAase) inserted into the OM OmpF porin, provide details of the initial interaction of the colicin central receptor (R)- and N-terminal T-domain with OM receptors/translocators. (II) Features of the translocon include: (a) high-affinity ( ≈ 10 M) binding of the E3 receptor-binding R-domain E3 to BtuB; (b) insertion of disordered colicin N-terminal domain into the OmpF trimer; (c) binding of the N-terminus, documented for colicin E9, to the TolB protein on the periplasmic side of OmpF. Reinsertion of the colicin N-terminus into the second of the three pores in OmpF implies a colicin anchor site on the periplasmic side of OmpF. Read More

Biochem J 2018 Dec 6;475(23):3707-3723. Epub 2018 Dec 6.

MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, U.K.

Reversible phosphorylation of proteins is a post-translational modification that regulates all aspect of life through the antagonistic action of kinases and phosphatases. Protein kinases are well characterized, but protein phosphatases have been relatively neglected. Protein phosphatase 1 (PP1) catalyzes the dephosphorylation of a major fraction of phospho-serines and phospho-threonines in cells and thereby controls a broad range of cellular processes. Read More