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Biochem J 2019 Apr 18;476(8):1221-1225. Epub 2019 Apr 18.

Biochem J 2019 Apr 18;476(8):1205-1219. Epub 2019 Apr 18.

Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC), 28049 Madrid, Spain.

The diacylglycerol kinases (DGK) are lipid kinases that transform diacylglycerol (DAG) into phosphatidic acid (PA) in a reaction that terminates DAG-based signals. DGK provide negative regulation to conventional and novel protein kinase C (PKC) enzymes, limiting local DAG availability in a tissue- and subcellular-restricted manner. Defects in the expression/activity of certain DGK isoforms contribute substantially to cognitive impairment and mental disorders. Read More

Biochem J 2019 Apr 16. Epub 2019 Apr 16.

Department of Physiology, Jinan University, Jinan University, 601 Huangpu Avenue West, Guangzhou, 510632, China.

Nutrient deficiency develops frequently in nasopharyngeal carcinoma cell (CNE-2Z) due to the characteristics of aggregation and uncontrolled proliferation. Therefore, starvation can induce autophagy in these cells. Chloride channel3 (ClC-3), a member of the chloride channel family, is involved in various biological processes. Read More

Biochem J 2019 Apr 16. Epub 2019 Apr 16.

Biochemistry and Genetics, La Trobe University, Bundoora, 3086, Australia

Poxviruses encode many proteins that enable them to evade host anti-viral defense mechanisms. Spi-2 proteins, including Cowpox virus CrmA, suppress anti-viral immune responses and contribute to poxviral pathogenesis and lethality. These proteins are "serpin" protease inhibitors, which function via a pseudosubstrate mechanism involving initial interactions between the protease and a cleavage site within the serpin. Read More

Biochem J 2019 Apr 15;476(7):1159-1172. Epub 2019 Apr 15.

Molecular Plant Biology, Department of Biochemistry, University of Turku, FI-20014 Turku, Finland

Photosynthesis is a highly regulated process in photoautotrophic cells. The main goal of the regulation is to keep the basic photosynthetic reactions, i.e. Read More

Biochem J 2019 Apr 15;476(7):1149-1158. Epub 2019 Apr 15.

Department of Molecular and Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Sherrington Building, Ashton Street, Liverpool L69 3GE, U.K.

Adverse drug reactions (ADRs) are the unintended side effects of drugs. They are categorised as either predictable or unpredictable drug-induced injury and may be exhibited after a single or prolonged exposure to one or multiple compounds. Historically, toxicology studies rely heavily on animal models to understand and characterise the toxicity of novel compounds. Read More

Biochem J 2019 Apr 15. Epub 2019 Apr 15.

Division of Structural Biology & Bio-informatics, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata, 700 032, India

Per-Arnt-Sim (PAS) domains are structurally conserved and present in numerous proteins throughout all branches of the phylogenetic tree. Although PAS domain containing proteins are major players for the adaptation to environmental stimuli in both prokaryotic and eukaryotic organisms, these types of proteins are still uncharacterized in the trypanosomatid parasites, and In addition, PAS containing phosphoglycerate kinase protein is uncharacterized in the literature. Here, we report a PAS domain containing phosphoglycerate kinase (LmPAS-PGK) in the unicellular pathogen The modeled structure of N-terminal of this protein exhibits four anti-parallel β sheets centrally flanked by α helices, which is similar to the characteristic signature of PAS domain. Read More

Biochem J 2019 Apr 10;476(7):1105-1107. Epub 2019 Apr 10.

Department of Biology, Washington University in St. Louis, St. Louis, MO 63130, U.S.A.

Nitrilases are versatile enzymes that hydrolyze nitriles to carboxylic acids and ammonia, but many members of this family lack defined biological functions. In plants, nitrilases have been associated with detoxification of cyanide-containing compounds and auxin biosynthesis; however, recent work suggests that the chemical versatility of these proteins contributes to metabolite repair. In this issue of the , Niehaus et al. Read More

Biochem J 2019 Apr 10;476(7):1083-1104. Epub 2019 Apr 10.

Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, U.S.A.

Long noncoding RNAs (lncRNAs) are transcripts that do not code for proteins, but nevertheless exert regulatory effects on various biochemical pathways, in part via interactions with proteins, DNA, and other RNAs. LncRNAs are thought to regulate transcription and other biological processes by acting, for example, as guides that target proteins to chromatin, scaffolds that facilitate protein-protein interactions and complex formation, and orchestrators of phase-separated compartments. The study of lncRNAs has reached an exciting time, as recent advances in experimental and computational methods allow for genome-wide interrogation of biochemical and biological mechanisms of these enigmatic transcripts. Read More

Biochem J 2019 Apr 8. Epub 2019 Apr 8.

Kyungpook National University, Daegu, Korea, Republic of

Communications between various organelle-organelles play an essential role in cell survival. The cross-talk between mitochondria and vacuoles come up with the vital roles of the intercompartmental process. In this study, we found a couple of cell death features, membrane damage, and apoptosis using antimicrobial peptide from American Cockroach. Read More

Biochem J 2019 Apr 3. Epub 2019 Apr 3.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.

αδ-Bungarotoxins, a novel group of long-chain α-neurotoxins, manifest different affinity to two agonist/competitive antagonist binding sites of muscle-type nicotinic acetylcholine receptors, being more active at the interface of α-δ-subunits. Three isoforms (αδ-BgTx-1-3) were identified in Malayan Krait ( ) from Thailand by genomic DNA analysis; two of them (αδ-BgTx-1 and 2) were isolated from its venom. The toxins comprise 73 amino acid residues and 5 disulfide bridges, being homologous to α-bungarotoxin (α-BgTx), a classical blocker of muscle-type and neuronal α7, α8, and α9α10 nicotinic acetylcholine receptors. Read More

Biochem J 2019 Mar 27;476(6):1005-1008. Epub 2019 Mar 27.

Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia

Moloney leukemia virus 10 (MOV10) is an interferon-inducible RNA helicase that has been implicated in a broad range of cellular functions, including modulating the replication of a diverse range of viruses. However, the mechanisms by which MOV10 promotes or inhibits the replication of particular viruses have not been well defined. A recent paper published in the by Li et al. Read More

Biochem J 2019 Mar 26. Epub 2019 Mar 26.

Karmanos Cancer Institute, 110 East Warren Avenue, DETROIT, Michigan, 48201, United States.

Tumors can be therapeutically targeted with novel antifolates (e.g., AGF94) that are selectively transported by the human proton-coupled folate transporter (hPCFT). Read More

Biochem J 2019 Apr 10;476(7):1137-1148. Epub 2019 Apr 10.

Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, U.S.A.

Intracellular protons and calcium ions are two major chemical factors that regulate connexin43 (Cx43) gap junction communication and the synergism or antagonism between pH and Ca has been questioned for decades. To assess the ability of Ca ions to modulate Cx43 junctional conductance () in the absence of pH-sensitivity, patch clamp experiments were performed on Neuroblastoma-2a (N2a) cells or neonatal mouse ventricular myocytes (NMVMs) expressing either full-length Cx43 or the Cx43-M257 (Cx43K258stop) mutant protein, a carboxyl-terminus (CT) truncated version of Cx43 lacking pH-sensitivity. The addition of 1 μM ionomycin to normal calcium saline reduced Cx43 or Cx43-M257 to zero within 15 min of perfusion. Read More

Biochem J 2019 Apr 15;476(7):1173-1189. Epub 2019 Apr 15.

Department of Chemistry, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark

The membrane protease γ-secretase cleaves the C99 fragment of the amyloid precursor protein, thus producing the Aβ peptides central to Alzheimer's disease. Cryo-electron microscopy has provided the topology but misses the membrane and loop parts that contribute to substrate binding. We report here an essentially complete atomic model of C99 within wild-type γ-secretase that respects all the experimental constraints and additionally describes loop, helix, and C99 substrate dynamics in a realistic all-atom membrane. Read More

Biochem J 2019 Mar 22;476(6):931-950. Epub 2019 Mar 22.

Department of Biology, University of Vermont, 109 Carrigan Drive, 120A Marsh Life Sciences, Burlington, VT 05405, U.S.A.

The iscoidin, U, and CCL omain-containing (DCBLD) receptor family are composed of the type-I transmembrane proteins DCBLD1 and DCBLD2 (also ESDN and CLCP1). These proteins are highly conserved across vertebrates and possess similar domain structure to that of neuropilins, which act as critical co-receptors in developmental processes. Although DCBLD1 remains largely uncharacterized, the functional and mechanistic roles of DCBLD2 are emerging. Read More

Biochem J 2019 Apr 10;476(7):1121-1135. Epub 2019 Apr 10.

Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB3 0AS, U.K.

Late embryogenesis abundant (LEA) proteins comprise a diverse family whose members play a key role in abiotic stress tolerance. As intrinsically disordered proteins, LEA proteins are highly hydrophilic and inherently stress tolerant. They have been shown to stabilise multiple client proteins under a variety of stresses, but current hypotheses do not fully explain how such broad range stabilisation is achieved. Read More

Biochem J 2019 Apr 10;476(7):1109-1119. Epub 2019 Apr 10.

Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands

The biologically important carnitine biosynthesis pathway in humans proceeds via four enzymatic steps. The first step in carnitine biosynthesis is catalyzed by trimethyllysine hydroxylase (TMLH), a non-heme Fe(II) and 2-oxoglutarate (2OG)-dependent oxygenase, which catalyzes the stereospecific hydroxylation of (2)--trimethyllysine to (2,3)-3-hydroxy--trimethyllysine. Here, we report biocatalytic studies on human TMLH and its 19 variants introduced through site-directed mutagenesis. Read More

Biochem J 2019 Apr 4;476(7):1053-1082. Epub 2019 Apr 4.

Chair of Drug and Cosmetics Biotechnology, Faculty of Chemistry, Warsaw University of Technology, Warsaw, Poland

Protein biosynthesis is energetically costly, is tightly regulated and is coupled to stress conditions including glucose deprivation. RNA polymerase III (RNAP III)-driven transcription of tDNA genes for production of tRNAs is a key element in efficient protein biosynthesis. Here we present an analysis of the effects of altered RNAP III activity on the proteome and metabolism under glucose-rich conditions. Read More

Biochem J 2019 Mar 29;476(6):1021-1035. Epub 2019 Mar 29.

Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, China

Semen-derived amyloid fibrils, comprising SEVI (semen-derived enhancer of viral infection) fibrils and SEM1 fibrils, could remarkably enhance HIV-1 sexual transmission and thus are potential targets for the development of an effective microbicide. Previously, we found that ADS-J1, apart from being an HIV-1 entry inhibitor, could also potently inhibit seminal amyloid fibrillization and block fibril-mediated enhancement of viral infection. However, the remodeling effects of ADS-J1 on mature seminal fibrils were unexplored. Read More

Biochem J 2019 Apr 15;476(7):1191-1203. Epub 2019 Apr 15.

Centre for Organismal Studies (COS) Heidelberg, Heidelberg University, Heidelberg, Germany

Plant γ-glutamylcysteine ligase (GCL), catalyzing the first and tightly regulated step of glutathione (GSH) biosynthesis, is redox-activated via formation of an intramolecular disulfide bond. , redox-activation of recombinant GCL protein causes formation of homo-dimers. Here, we have investigated whether dimerization occurs and if so whether it contributes to redox-activation. Read More

Biochem J 2019 Mar 29;476(6):1009-1020. Epub 2019 Mar 29.

Structural Bioinformatics Laboratory, Biochemistry, Faculty of Science and Engineering, Åbo Akademi University, Tykistökatu 6A, 20520 Turku, Finland

Spermidine is a ubiquitous polyamine synthesized by spermidine synthase (SPDS) from the substrates, putrescine and decarboxylated S-adenosylmethionine (dcAdoMet). SPDS is generally active as homodimer, but higher oligomerization states have been reported in SPDS from thermophiles, which are less specific to putrescine as the aminoacceptor substrate. Several crystal structures of SPDS have been solved with and without bound substrates and/or products as well as inhibitors. Read More

Biochem J 2019 Apr 4;476(7):1037-1051. Epub 2019 Apr 4.

Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, U.K.

The group A p21-activated kinases (PAKs) exist in an auto-inhibited form until activated by GTPase binding and auto-phosphorylation. In the auto-inhibited form, a regulatory domain binds to the kinase domain (KD) blocking the binding of substrates, and CDC42 or Rac binding to the regulatory domain relieves this auto-inhibition allowing auto-phosphorylation on the KD activation loop. We have determined the crystal structure of the PAK3 catalytic domain and by small angle X-ray scattering, the solution-phase structures of full-length inactive PAK1 and PAK3. Read More

Biochem J 2019 Mar 6;476(5):779-781. Epub 2019 Mar 6.

Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden

Colorectal cancer is one of the most common forms of cancer in the world, with more than half a million new cases annually. Amongst the most promising new therapies, niclosamide-an FDA-approved drug for treating tapeworm infections-is being assessed in a stage II clinical trial for the treatment of metastatic colorectal cancer. Despite this advanced stage of research, the underlying mechanisms behind its actions remain uncertain. Read More

Biochem J 2019 Mar 6;476(5):769-778. Epub 2019 Mar 6.

Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, U.K.

In mammals, the B-cell lineage arises from pluripotent progenitors in the bone marrow. During their development, B-cells undergo lineage specification and commitment, followed by expansion and selection. These processes are mediated by regulated changes in gene expression programmes, rearrangements of immunoglobulin (Ig) genes, and well-timed rounds of proliferation and apoptosis. Read More

Biochem J 2019 Mar 22;476(6):951-963. Epub 2019 Mar 22.

Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, U.S.A.

High-density lipoproteins (HDLs) facilitate reverse cholesterol transport, a process in which HDL removes cholesterol from circulation and carries it to the liver for biliary excretion. Reverse cholesterol transport is also facilitated by HDL's high-affinity receptor, scavenger receptor-BI (SR-BI), by mechanisms that are not fully understood. To improve our understanding of SR-BI function, we previously solved the NMR (nuclear magnetic resonance) structure of a peptide encompassing amino acids 405-475 of SR-BI. Read More

Biochem J 2019 Mar 22;476(6):991-1003. Epub 2019 Mar 22.

Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, Telangana, India

Natural product ovalicin and its synthetic derivative TNP-470 have been extensively studied for their antiangiogenic property, and the later reached phase 3 clinical trials. They covalently modify the conserved histidine in Type 2 methionine aminopeptidases (MetAPs) at nanomolar concentrations. Even though a similar mechanism is possible in Type 1 human MetAP, it is inhibited only at millimolar concentration. Read More

Biochem J 2019 Mar 22;476(6):975-989. Epub 2019 Mar 22.

School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, U.K.

Ferritins are a large family of intracellular proteins that protect the cell from oxidative stress by catalytically converting Fe(II) into less toxic Fe(III) and storing iron minerals within their core. Encapsulated ferritins (EncFtn) are a sub-family of ferritin-like proteins, which are widely distributed in all bacterial and archaeal phyla. The recently characterized EncFtn displays an unusual structure when compared with classical ferritins, with an open decameric structure that is enzymatically active, but unable to store iron. Read More

Biochem J 2019 Feb 28;476(4):705-718. Epub 2019 Feb 28.

Randall Centre for Cell and Molecular Biophysics, King's College London, New Hunts House, London SE1 1UL, U.K.

Integrins are heterodimeric transmembrane receptors that play an essential role in enabling cells to sense and bind to extracellular ligands. Activation and clustering of integrins leads to the formation of focal adhesions at the plasma membrane that subsequently initiate signalling pathways to control a broad range of functional endpoints including cell migration, proliferation and survival. The α4 and α9 integrins form a small sub-family of receptors that share some specific ligands and binding partners. Read More

Biochem J 2019 Feb 28;476(4):699-703. Epub 2019 Feb 28.

School of Dental Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4BW, U.K.

The ability of opportunistic pathogens such as Group A (GAS) to transition between mucosal colonisation and invasive disease requires complex systems for adapting to markedly different host environments. The battle to acquire essential trace metals such as manganese and iron from the host is central to pathogenesis. Using a molecular genetic approach, Turner et al. Read More

Biochem J 2019 Mar 22;476(6):965-974. Epub 2019 Mar 22.

Department of Botany and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innsbruck, Austria.

High seed quality is a key trait to achieve successful crop establishment required for optimum yield and sustainable production. Seed storage conditions greatly impact two key seed quality traits; seed viability (ability to germinate and produce normal seedlings) and vigour (germination performance). Accumulated oxidative damage accompanies the loss of seed vigour and viability during ageing, indicating that redox control is key to longevity. Read More

Biochem J 2019 Mar 15;476(5):889-907. Epub 2019 Mar 15.

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra 400076, India

The human islet amyloid polypeptide (hIAPP) or amylin is the major constituent of amyloidogenic aggregates found in pancreatic islets of type 2 diabetic patients that have been associated with β-cell dysfunction and/or death associated with type 2 diabetes mellitus (T2DM). Therefore, developing and/or identifying inhibitors of hIAPP aggregation pathway and/or compound that can mediate disaggregation of preformed aggregates holds promise as a medical intervention for T2DM management. In the current study, the anti-amyloidogenic potential of Azadirachtin (AZD)-a secondary metabolite isolated from traditional medicinal plant Neem ()-was investigated by using a combination of biophysical and cellular assays. Read More

Biochem J 2019 Mar 15;476(5):909-930. Epub 2019 Mar 15.

Molecular Biology Division, Bhabha Atomic Research Centre, Mumbai 400085, India

, an extremely radioresistant bacterium has a multipartite genome system and ploidy. Mechanisms underlying such types of bacterial genome maintenance and its role in extraordinary radioresistance are not known in this bacterium. Chromosome I (Chr I), chromosome II (Chr II) and megaplasmid (Mp) encode its own set of genome partitioning proteins. Read More

Biochem J 2019 Mar 12;476(5):827-842. Epub 2019 Mar 12.

Laboratory of Molecular Life Sciences, Department of Biotechnology, Akita Prefectural University, Akita 010-0195, Japan

To closely mimic physiological conditions, low oxygen cultures have been employed in stem cell and cancer research. Although oxygen concentrations in tissues are often much lower than ambient 21% O (ranging from 3.6 to 12. Read More

Biochem J 2019 Mar 12;476(5):859-873. Epub 2019 Mar 12.

Department of Chemistry and Biochemistry, School of Mathematics and Natural Sciences, University of Southern Mississippi, Hattiesburg, MS 39406, U.S.A.

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's 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 Mar 12;476(5):875-887. Epub 2019 Mar 12.

Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt, 60438 Frankfurt, 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 (Unc-51-like autophagy activating kinase 1) 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 (Unc-51-like autophagy activating kinase 2). Read More

Biochem J 2019 Mar 12;476(5):843-857. Epub 2019 Mar 12.

Max Planck Institute for Plant Breeding Research, 50829 Cologne, 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 Mar 12;476(5):809-826. Epub 2019 Mar 12.

Department of Chemistry, University of Oxford, Oxford OX1 3QR, U.K.

SPH (self-incompatibility protein homologue) proteins are a large family of small, disulfide-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 nuclear magnetic resonance (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 Mar 6;476(5):783-794. Epub 2019 Mar 6.

Department of Plant and Environmental Sciences, University of Copenhagen, Copenhagen, Denmark

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 the present 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 28;476(4):759-768. Epub 2019 Feb 28.

Division of Human Reproduction and Developmental Genetics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, 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 (host cell factor), 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 28;476(4):733-746. Epub 2019 Feb 28.

Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Collaborative Innovation Center of Chemical Science and Engineering, School of Pharmaceutical Science and Technology, Tianjin University, 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 sulfoacetaldehyde, which is generated by transamination of taurine, forming hydroxyethylsulfonate (isethionate) as a waste product. In the present study, the crystal structure of IsfD in a ternary complex with NADPH and isethionate was solved at 2. Read More

Biochem J 2019 Feb 28;476(4):719-732. Epub 2019 Feb 28.

Department of Protein Synthesis Enzymology, Institute of Molecular Biology and Genetics of the NAS of Ukraine, 150 Zabolotnogo Str., 03143 Kyiv, 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 28;476(4):747-758. Epub 2019 Feb 28.

Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, Austin, TX 78750, U.S.A.

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