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    1 OF 1363

    Structure-related roles for the conservation of the HIV-1 fusion peptide sequence revealed by NMR.
    Biochemistry 2017 Sep 20. Epub 2017 Sep 20.
    Despite extensive characterization of the human immunodeficiency virus type-1 (HIV-1) hydrophobic fusion peptide (FP), the structure-function relationships underlying its extraordinary degree of conservation remain poorly understood. Specifically, the fact that the tandem repeat of the tripeptide FLGFLG is absolutely conserved suggests that high hydrophobicity may not suffice to unleash FP function. Here, we have compared the NMR structures adopted in nonpolar media by two FP surrogates, wtFP-tag and scrFP-tag, which had equal hydrophobicity but contained wild-type and scrambled core sequences LFLGFLG and FGLLGFL, respectively. Read More

    The structure of an insecticide sequestering carboxylesterase from the disease vector Culex quinquefasciatus: what makes an enzyme a good insecticide sponge?
    Biochemistry 2017 Sep 20. Epub 2017 Sep 20.
    Carboxylesterase (CBE)-mediated metabolic resistance to organophosphate and carbamate insecticides is a major problem for the control of insect disease vectors, such as the mosquito. The most common mechanism involves overexpression of CBEs that bind to the insecticide with high affinity, thereby sequestering them before they can interact with their target. However, the absence of any structure for an insecticide-sequestering CBE limits our understanding of the molecular basis for this process. Read More

    Recognition of DNA Supercoil Geometry by Mycobacterium tuberculosis Gyrase.
    Biochemistry 2017 Sep 18. Epub 2017 Sep 18.
    Mycobacterium tuberculosis encodes only a single type II topoisomerase, gyrase. As a result, this enzyme likely carries out the cellular functions normally performed by canonical gyrase and topoisomerase IV, both in front of and behind the replication fork. In addition, it is the sole target for quinolone antibacterials in this species. Read More

    Manipulating protein-protein interactions in NRPS type II PCPs.
    Biochemistry 2017 Sep 18. Epub 2017 Sep 18.
    In an effort to elucidate and engineer interactions in type II nonribosomal peptide synthetases, we analyzed biomolecular recognition between the essential peptidyl carrier proteins and adenylation domains using NMR spectroscopy, molecular dynamics, and mutational studies. Three peptidyl carrier proteins, PigG, PltL, and RedO, in addition to their cognate adenylation domains, PigI, PltF, and RedM, were investigated for their cross species activity. Of the three peptidyl carrier proteins, only PigG, showed substantial cross-pathway activity. Read More

    Fluorotryptophan incorporation modulates the structure and stability of transthyretin in a site-specific manner.
    Biochemistry 2017 Sep 18. Epub 2017 Sep 18.
    Abnormal deposition of aggregated wild-type (WT) human transthyretin (TTR) and its pathogenic variants is responsible for cardiomyopathy and neuropathy related to TTR amyloidosis. The tryptophan (Trp) fluorescence measurements typically used to study structural changes of TTR do not yield site-specific information on the two Trp residues per TTR protomer. To obtain such information, tryptophan labeled with fluorine at the 5 and 6 positions (5FW and 6FW) was incorporated into TTR. Read More

    Inhibition of hAM amyloidogenesis by hAM-fragment peptides: exploring the effects of serine residues and oligomerization upon inhibitory potency.
    Biochemistry 2017 Sep 18. Epub 2017 Sep 18.
    To date, fragments from within the amyloidogenic-patch region of human amylin (hAM) have been shown to aggregate independently of the full-length peptide. In this study, we show that under certain conditions, both oligomers of NFGAILSS and the monomeric form are capable of inhibiting the aggregation of the full-length hAM sequence. The inhibition, rather than aggregate seeding, observed with the soluble portion of aged NFGAILSS solutions was particularly striking occurring at far sub-stoichiometric levels. Read More

    Expression, Purification, and Activity of ActhiS, a Thiazole Biosynthesis Enzyme from Acremonium chrysogenum.
    Biochemistry (Mosc) 2017 Jul;82(7):852-860
    China State Institute of Pharmaceutical Industry, Zhangjiang Institute, Shanghai, 201203, China.
    Thiamine pyrophosphate is an essential coenzyme in all organisms. Its biosynthesis involves independent syntheses of the precursors, pyrimidine and thiazole, which are then coupled. In our previous study with overexpressed and silent mutants of ActhiS (thiazole biosynthesis enzyme from Acremonium chrysogenum), we found that the enzyme level correlated with intracellular thiamine content in A. Read More

    Effect of Low Temperature on Globin Expression, Respiratory Metabolic Enzyme Activities, and Gill Structure of Litopenaeus vannamei.
    Biochemistry (Mosc) 2017 Jul;82(7):844-851
    Ministry of Education, Huazhong Agricultural University, College of Fishery, Key Lab of Freshwater Animal Breeding, Key Lab of Agricultural Animal Genetics, Breeding, and Reproduction, Wuhan, 430070, PR China.
    Low temperature frequently influences growth, development, and even survival of aquatic animals. In the present study, physiological and molecular responses to low temperature in Litopenaeus vannamei were investigated. The cDNA sequences of two oxygen-carrying proteins, cytoglobin (Cygb) and neuroglobin (Ngb), were isolated. Read More

    New Data on Programmed Risks of Death in Normal Mice and Mutants with Growth Delay.
    Biochemistry (Mosc) 2017 Jul;82(7):834-843
    Bach Institute of Biochemistry, Research Center of Biotechnology, Russian Academy of Sciences, Moscow, 119071, Russia.
    Study of the lifespans of normal (non mutant) mice and growth delay mutants has shown that mortality rates for both kinds of animals exhibit reproducible fluctuations. In the case of the mutant mice, the positions of peaks on the differential mortality curves (mortality rate plotted against lifespan) coincided in different-sex groups of animals and in same-sex subgroups of animals. Differential mortality curves of the mutant mice also had a peak at 1 month of age that was absent from the differential mortality curves of the normal mice. Read More

    Omega-3 Polyunsaturated Fatty Acids Eicosapentaenoic Acid and Docosahexaenoic Acid Enhance Dexamethasone Sensitivity in Multiple Myeloma Cells by the p53/miR-34a/Bcl-2 Axis.
    Biochemistry (Mosc) 2017 Jul;82(7):826-833
    Binzhou Medical University, School of Pharmacy, Yantai, Shandong, 264003, PR China.
    Dexamethasone is widely used in multiple myeloma (MM) for its cytotoxic effects on lymphoid cells. However, many MM patients are resistant to dexamethasone, although some can benefit from dexamethasone treatment. In this study, we noted that ω-3 polyunsaturated fatty acids (PUFAs) enhanced the dexamethasone sensitivity of MM cells by inducing cell apoptosis. Read More

    Escherichia coli Signal Peptidase Recognizes and Cleaves Archaeal Signal Sequence.
    Biochemistry (Mosc) 2017 Jul;82(7):821-825
    University of the Punjab, School of Biological Sciences, Lahore, 54590, Pakistan.
    Tk1884, an open reading frame encoding α-amylase in Thermococcus kodakarensis, was cloned with the native signal sequence and expressed in Escherichia coli. Heterologous gene expression resulted in secretion of the recombinant protein to the extracellular culture medium. Extracellular α-amylase activity gradually increased after induction. Read More

    Coupling of Translation Initiation and Termination Does Not Depend on the Mode of Initiation.
    Biochemistry (Mosc) 2017 Jul;82(7):816-820
    Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia.
    Recently we described a novel phenomenon observed during eukaryotic translation in a cell-free system: the coupling of initiation and termination on different mRNA molecules. Here we show that the phenomenon does not depend on a special mode of initiation. The mRNAs with certain leader sequences known to require different determinants for successful initiation were examined. Read More

    Intracellular Cargo Transport by Kinesin-3 Motors.
    Biochemistry (Mosc) 2017 Jul;82(7):803-815
    Centre for Mechanochemical Cell Biology, University of Warwick, Coventry, CV4 7AL, UK.
    Intracellular transport along microtubules enables cellular cargoes to efficiently reach the extremities of large, eukaryotic cells. While it would take more than 200 years for a small vesicle to diffuse from the cell body to the growing tip of a one-meter long axon, transport by a kinesin allows delivery in one week. It is clear from this example that the evolution of intracellular transport was tightly linked to the development of complex and macroscopic life forms. Read More

    EB-Family Proteins: Functions and Microtubule Interaction Mechanisms.
    Biochemistry (Mosc) 2017 Jul;82(7):791-802
    Dmitry Rogachev National Scientific and Practical Center of Pediatric Hematology, Oncology, and Immunology, Moscow, 117997, Russia.
    Microtubules are polymers of tubulin protein, one of the key components of cytoskeleton. They are polar filaments whose plus-ends usually oriented toward the cell periphery are more dynamic than their minus-ends, which face the center of the cell. In cells, microtubules are organized into a network that is being constantly rebuilt and renovated due to stochastic switching of its individual filaments from growth to shrinkage and back. Read More

    A New Concept of Action of Hemostatic Proteases on Inflammation, Neurotoxicity, and Tissue Regeneration.
    Biochemistry (Mosc) 2017 Jul;82(7):778-790
    Lomonosov Moscow State University, Faculty of Biology, Moscow, 119991, Russia.
    Key hemostatic serine proteases such as thrombin and activated protein C (APC) are signaling molecules controlling blood coagulation and inflammation, tissue regeneration, neurodegeneration, and some other processes. By interacting with protease-activated receptors (PARs), these enzymes cleave a receptor exodomain and liberate new amino acid sequence known as a tethered ligand, which then activates the initial receptor and induces multiple signaling pathways and cell responses. Among four PAR family members, APC and thrombin mainly act via PAR1, and they trigger divergent effects. Read More

    Design, Synthesis, and Some Aspects of the Biological Activity of Mitochondria-Targeted Antioxidants.
    Biochemistry (Mosc) 2017 Jul;82(7):760-777
    Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119991, Russia.
    This review summarizes for the first time data on the design and synthesis of biologically active compounds of a new generation - mitochondria-targeted antioxidants, which are natural (or synthetic) p-benzoquinones conjugated via a lipophilic linker with (triphenyl)phosphonium or ammonium cations with delocalized charge. It also describes the synthesis of mitochondria-targeted antioxidants - uncouplers of oxidative phosphorylation - based on fluorescent dyes. Read More

    Methylglyoxal and Small Heat Shock Proteins.
    Biochemistry (Mosc) 2017 Jul;82(7):751-759
    Lomonosov Moscow State University, Faculty of Biology, Moscow, 119991, Russia.
    Methylglyoxal is a highly reactive dicarbonyl compound formed during glucose metabolism and able to modify phospholipids, nucleic acids, and proteins belonging to the so-called dicarbonyl proteome. Small heat shock proteins participating in protection of the cell against different unfavorable conditions can be modified by methylglyoxal. The probability of methylglyoxal modification is increased in the case of distortion of glucose metabolism (diabetes), in the case of utilization of glycolysis as the main source of energy (malignancy), and/or at low rate of modified protein turnover. Read More

    Structure and Dynamics of Membrane Proteins and Membrane Associated Proteins with Native Bicelles from Eukaryotic Tissues.
    Biochemistry 2017 Sep 15. Epub 2017 Sep 15.
    In vitro studies of protein structure, function and dynamics typically preclude the complex range of molecular interactions found in living tissues. In vivo studies elucidate these complex relationships, yet they are typically incompatible with the extensive and controlled biophysical experiments available in vitro. We present an alternative approach by extracting membranes from eukaryotic tissues to produce native bicelles to capture the rich and complex molecular environment of in vivo studies while retaining the advantages of in vitro experiments. Read More

    Structural Evidence for the Dopamine-First Mechanism of Norcoclaurine Synthase.
    Biochemistry 2017 Sep 20. Epub 2017 Sep 20.
    Institute for Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London , Malet Street, London WC1E 7HX, U.K.
    Norcoclaurine synthase (NCS) is a Pictet-Spenglerase that catalyzes the first key step in plant benzylisoquinoline alkaloid metabolism, a compound family that includes bioactive natural products such as morphine. The enzyme has also shown great potential as a biocatalyst for the formation of chiral isoquinolines. Here we present new high-resolution X-ray crystallography data describing Thalictrum flavum NCS bound to a mechanism-inspired ligand. Read More

    Mechanoregulation of SM22α/Transgelin.
    Biochemistry 2017 Sep 12. Epub 2017 Sep 12.
    SM22α, also named transgelin, is an actin filament-associated protein in smooth muscle and fibroblast. Three decades after discovery, the biological function of SM22α remains under investigation. Here we report a novel finding that the expression and degradation of SM22α/transgelin is regulated by mechanical tension. Read More

    The Too Many Faces Of PD-L1: A Comprehensive Conformational Analysis Study.
    Biochemistry 2017 Sep 12. Epub 2017 Sep 12.
    In the current study, we focused on the immune-checkpoints PD-1 pathway and in particular on the ligand, PD-L1. We studied the conformational dynamics of PD-L1 through principal component analysis (PCA) of existing crystal structures combined with classical and accelerated molecular dynamics simulations. We identified the maximum structural displacements that take place in all PD-L1 crystal structures and in the MD trajectories. Read More

    Analysis of Plasmodium vivax Chloroquine Resistance Transporter (PvCRT) Mutant Isoforms.
    Biochemistry 2017 Sep 12. Epub 2017 Sep 12.
    Chloroquine (CQ) resistance (CQR) in Plasmodium falciparum malaria is widespread and has limited the use of CQ in many regions of the globe. Malaria caused by the related human parasite P. vivax is as widespread as is P. Read More

    Eukaryotic Ribosomal Expansion Segments as Antimicrobial Targets.
    Biochemistry 2017 Sep 12. Epub 2017 Sep 12.
    Diversity in eukaryotic rRNA structure and function offers possibilities of novel therapeutic targets. Unlike ribosomes of prokaryotes, eukaryotic ribosomes contain species-specific rRNA expansion segments (ESs) with idiosyncratic structures and functions that are essential and specific to some organisms. Here we investigate expansion segment 7 (ES7), one of the largest and most variable expansions of the eukaryotic ribosome. Read More

    Radical S-Adenosylmethionine Enzymes Involved in RiPP Biosynthesis.
    Biochemistry 2017 Sep 22. Epub 2017 Sep 22.
    Department of Chemistry, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
    Ribosomally synthesized and post-translationally modified peptides (RiPPs) display a diverse range of structures and continue to expand as a natural product class. Accordingly, RiPPs exhibit a wide array of bioactivities, acting as broad and narrow spectrum growth suppressors, antidiabetics, and antinociception and anticancer agents. Because of these properties, and the complex repertoire of post-translational modifications (PTMs) that give rise to these molecules, RiPP biosynthesis has been intensely studied. Read More

    Antiproliferative factor (APF) binds specifically to sites within the cytoskeleton-associated protein 4 (CKAP4) extracellular domain.
    BMC Biochem 2017 Sep 11;18(1):13. Epub 2017 Sep 11.
    Department of Basic Sciences, Geisinger Commonwealth School of Medicine, 525 Pine Street, Scranton, PA, 18509, USA.
    Background: Antiproliferative factor (APF) is a sialoglycopeptide elevated in the urine of patients with interstitial cystitis-a chronic, painful bladder disease. APF inhibits the proliferation of normal bladder epithelial cells and cancer cells in vitro, presumably by binding to its cellular receptor, cytoskeleton associated-protein 4 (CKAP4); however, the biophysical interaction of APF with CKAP4 has not been characterized previously. In this study, we used surface plasmon resonance (SPR) to explore the binding kinetics of the interaction of APF and as-APF (a desialylated APF analogue with full activity) to CKAP4. Read More

    Characterization of the Functional Variance in MbtH-like Protein Interactions with a Nonribosomal Peptide Synthetase.
    Biochemistry 2017 Sep 20. Epub 2017 Sep 20.
    Department of Bacteriology, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.
    Many nonribosomal peptide synthetases (NRPSs) require MbtH-like proteins (MLPs) for solubility or for activation of amino acid substrate by the adenylation domain. MLPs are capable of functional crosstalk with noncognate NRPSs at varying levels. Using enterobactin biosynthesis in Escherichia coli as a model MLP-dependent NRPS system, we use in vivo and in vitro techniques to characterize how seven noncognate MLPs influence the function of the enterobactin NRPS EntF when the cognate MLP, YbdZ, is absent. Read More

    Hydrophobic Collapse of the Intrinsically Disordered Transcription Factor Myc Associated Factor X.
    Biochemistry 2017 Sep 21. Epub 2017 Sep 21.
    Département de Chimie, Ecole Normale Supérieure, PSL Research University, UPMC Univ Paris 06, CNRS, Laboratoire des Biomolécules (LBM) , 24 rue Lhomond, 75005 Paris, France.
    The conformational space of the proto-oncogenic transcription factor Myc associated factor X (MAX) comprises a dynamic equilibrium between a stably folded coiled-coil homodimer and an intrinsically disordered ensemble of states. We show by means of nuclear magnetic resonance spectroscopy that the intrinsically disordered ensemble samples structures that are even as compact as the folded dimer. These extremely dense, hydrophobically collapsed globules might be of importance for interconversion between different conformations of intrinsically disordered proteins. Read More

    Quantitative Multiple-Reaction Monitoring Proteomic Analysis of Gβ and Gγ Subunits in C57Bl6/J Brain Synaptosomes.
    Biochemistry 2017 Sep 21. Epub 2017 Sep 21.
    Department of Pharmacology, Vanderbilt University , Nashville, Tennessee 37232-6600, United States.
    Gβγ dimers are one of the essential signaling units of activated G protein-coupled receptors (GPCRs). There are five Gβ and 12 Gγ subunits in humans; numerous studies have demonstrated that different Gβ and Gγ subunits selectively interact to form unique Gβγ dimers, which in turn may target specific receptors and effectors. Perturbation of Gβγ signaling can lead to impaired physiological responses. Read More

    Loss of Fourth Electron-Transferring Tryptophan in Animal (6-4) Photolyase Impairs DNA Repair Activity in Bacterial Cells.
    Biochemistry 2017 Sep 20. Epub 2017 Sep 20.
    Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay , 91198 Gif-sur-Yvette cedex, France.
    (6-4) photolyases [(6-4)PLs] are flavoproteins that use blue light to repair the ultraviolet-induced pyrimidine(6-4)pyrimidone photoproduct in DNA. Their flavin adenine dinucleotide (FAD) cofactor can be reduced to its repair-active FADH(-) form by a photoinduced electron transfer reaction. In animal (6-4)PLs, a chain of four Trp residues was suggested to be involved in a stepwise transfer of an oxidation hole from the flavin to the surface of the protein. Read More

    Specificity and Speed: Tethered Photopharmacology.
    Biochemistry 2017 Sep 14. Epub 2017 Sep 14.
    Department of Chemistry and Center for Integrated Protein Science Munich, Ludwig-Maximilians-Universität München , Butenandtstrasse 5-13, 81377 Munich, Germany.
    Genetics and pharmacology are often seen as two distinct approaches to interrogating, elucidating, and manipulating biological systems. The former is renowned for its precision whereas the latter for its fast kinetics, reversibility, and practicality. Here, we show that both can be joined as "tethered pharmacology", wherein a genetically programmed bioconjugation site provides selectivity and a tethered pharmacophore provides function. Read More

    Probing the Role of the Heme Distal and Proximal Environment in Ligand Dynamics in the Signal Transducer Protein HemAT by Time-Resolved Step-Scan FTIR and Resonance Raman Spectroscopy.
    Biochemistry 2017 Sep 21. Epub 2017 Sep 21.
    Department of Chemistry, University of Cyprus , P.O. Box 20537, 1678 Nicosia, Cyprus.
    HemAT is a heme-containing oxygen sensor protein that controls aerotaxis. Time-resolved step-scan FTIR studies were performed on the isolated sensor domain and full-length HemAT proteins as well as on the Y70F (B-helix), L92A (E-helix), T95A (E-helix), and Y133F (G-helix) mutants to elucidate the effect of the site-specific mutations on the ligand dynamics subsequent to CO photolysis. The mutations aimed to perturb H-bonding and electrostatic interactions near the heme Fe-bound gaseous ligand (CO) and the heme proximal environment. Read More

    The Phe-Ile Zipper: Specific Interaction Motif Drives Antiparallel Coiled-Coil Hexamer Formation.
    Biochemistry 2017 Sep 6. Epub 2017 Sep 6.
    Coiled coils are a robust motif for exploring amino acid interactions, generating unique supramolecular structures, and expanding properties of biological based ma- terials. A recently discovered antiparallel coiled-coil hexamer (ACC-Hex, peptide 1) exhibits a unique interaction in which Phe and Ile residues from adjacent α-helices interact to form a Phe-Ile zipper within the hydrophobic core. Analysis of the X-ray crystallographic structure of ACC-Hex suggests that the stability of the six-helix bundle relies on specific interactions between the Phe and Ile residues. Read More

    Periplasmic Binding Protein Dimer Has a Second Allosteric Event Tied to Ligand Binding.
    Biochemistry 2017 Sep 22. Epub 2017 Sep 22.
    Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee , Knoxville, Tennessee 37996, United States.
    The ligand-induced conformational changes of periplasmic binding proteins (PBP) play a key role in the acquisition of metabolites in ATP binding cassette (ABC) transport systems. This conformational change allows for differential recognition of the ligand occupancy of the PBP by the ABC transporter. This minimizes futile ATP hydrolysis in the transporter, a phenomenon in which ATP hydrolysis is not coupled to metabolite transport. Read More

    His-Tag-Mediated Dimerization of Chemoreceptors Leads to Assembly of Functional Nanoarrays.
    Biochemistry 2017 Sep 22. Epub 2017 Sep 22.
    Department of Biology, Leiden University , 2333 Leiden, The Netherlands.
    Transmembrane chemotaxis receptors are found in bacteria in extended hexagonal arrays stabilized by the membrane and by cytosolic binding partners, the kinase CheA and coupling protein CheW. Models of array architecture and assembly propose receptors cluster into trimers of dimers that associate with one CheA dimer and two CheW monomers to form the minimal "core unit" necessary for signal transduction. Reconstructing in vitro chemoreceptor ternary complexes that are homogeneous and functional and exhibit native architecture remains a challenge. Read More

    Chiral Ramachandran Plots I: Glycine.
    Biochemistry 2017 Sep 21. Epub 2017 Sep 21.
    Institute of Chemistry, The Hebrew University of Jerusalem , Jerusalem 9190401, Israel.
    Ramachandran plots (RPs) map the wealth of conformations of the polypeptide backbone and are widely used to characterize protein structures. A limitation of the RPs is that they are based solely on two dihedral angles for each amino acid residue and provide therefore only a partial picture of the conformational richness of the protein. Here we extend the structural RP analysis of proteins from a two-dimensional (2D) map to a three-dimensional map by adding the quantitative degree of chirality-the continuous chirality measure (CCM)-of the amino acid residue at each point in the RP. Read More

    OleB from Bacterial Hydrocarbon Biosynthesis Is a β-Lactone Decarboxylase That Shares Key Features with Haloalkane Dehalogenases.
    Biochemistry 2017 Sep 19. Epub 2017 Sep 19.
    Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota , Minneapolis, Minnesota 55455, United States.
    OleB is an α/β-hydrolase found in bacteria that biosynthesize long-chain olefinic hydrocarbons, but its function has remained obscure. We report that OleB from the Gram-negative bacterium Xanthomonas campestris performs an unprecedented β-lactone decarboxylation reaction, to complete cis-olefin biosynthesis. OleB reactions monitored by (1)H nuclear magnetic resonance spectroscopy revealed a selectivity for decarboxylating cis-β-lactones and no discernible activity with trans-β-lactones, consistent with the known configuration of pathway intermediates. Read More

    High-Affinity Interactions of Beryllium(2+) with Phosphatidylserine Result in a Cross-Linking Effect Reducing Surface Recognition of the Lipid.
    Biochemistry 2017 Sep 20. Epub 2017 Sep 20.
    Department of Biology, University of Maryland , College Park, Maryland 20742, United States.
    Beryllium has multiple industrial applications, but its manufacture is associated with a serious occupational risk of developing chronic inflammation in the lungs known as berylliosis, or chronic beryllium disease. Although the Be(2+)-induced abnormal immune responses have recently been linked to a specific MHC-II allele, the nature of long-lasting granulomas is not fully understood. Here we show that Be(2+) binds with a micromolar affinity to phosphatidylserine (PS), the major surface marker of apoptotic cells. Read More

    Undecaprenyl Phosphate Phosphatase Activity of Undecaprenol Kinase Regulates the Lipid Pool in Gram-Positive Bacteria.
    Biochemistry 2017 Sep 21. Epub 2017 Sep 21.
    Genomics Research Center, Academia Sinica , Taipei 115, Taiwan.
    Bacteria cell walls contain many repeating glycan structures, such as peptidoglycans, lipopolysaccharides, teichoic acids, and capsular polysaccharides. Their synthesis starts in the cytosol, and they are constructed from a glycan lipid carrier, undecaprenyl phosphate (C55P), which is essential for cell growth and survival. The lipid derivative undecaprenol (C55OH) is predominant in many Gram-positive bacteria but has not been detected in Gram-negative bacteria; its origin and role have thus remained unknown. Read More

    Characterization of Hsp90 Co-Chaperone p23 Cleavage by Caspase-7 Uncovers a Peptidase-Substrate Interaction Involving Intrinsically Disordered Regions.
    Biochemistry 2017 Sep 18. Epub 2017 Sep 18.
    Department of Pharmacology-Physiology and ‡Department of Biochemistry, Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Faculty of Medicine and Health Sciences , 3001, 12th Avenue North, Sherbrooke, QC J1H 5N4, Canada.
    Caspases are cysteinyl peptidases involved in inflammation and apoptosis during which hundreds of proteins are cleaved by executioner caspase-3 and -7. Despite the fact that caspase-3 has a higher catalytic activity, caspase-7 is more proficient at cleaving poly(ADP ribose) polymerase 1 (PARP1) because it uses an exosite within its N-terminal domain (NTD). Here, we demonstrate that molecular determinants also located in the NTD enhance the recognition and proteolysis of the Hsp90 co-chaperone p23. Read More

    DNA Polymerase β Cancer-Associated Variant I260M Exhibits Nonspecific Selectivity toward the β-γ Bridging Group of the Incoming dNTP.
    Biochemistry 2017 Sep 20. Epub 2017 Sep 20.
    Department of Therapeutic Radiology and Department of Genetics, Yale University School of Medicine , New Haven, Connecticut 06520, United States.
    The hydrophobic hinge region of DNA polymerase β (pol β) is located between the fingers and palm subdomains. The hydrophobicity of the hinge region is important for maintaining the geometry of the binding pocket and for the selectivity of the enzyme. Various cancer-associated pol β variants in the hinge region have reduced fidelity resulting from a decreased discrimination at the level of dNTP binding. Read More

    Structural and Functional Analyses of Periplasmic 5'-Methylthioadenosine/S-Adenosylhomocysteine Nucleosidase from Aeromonas hydrophila.
    Biochemistry 2017 Sep 20. Epub 2017 Sep 20.
    Department of Bioengineering, College of Life Science, Dalian Minzu University , Dalian 116600, Liaoning, China.
    The Gram-negative, rod-shaped bacterium Aeromonas hydrophila has two multifunctional 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) enzymes, MtaN-1 and MtaN-2, that differ from those in other bacteria. These proteins are essential for several metabolic pathways, including biological methylation, polyamine biosynthesis, methionine recycling, and bacterial quorum sensing. To gain insight into how these two proteins function, we determined four high-resolution crystal structures of MtaN-1 in its apo form and in complex with the substrates S-adenosyl-l-homocysteine, 5'-methylthioadenosine, and 5'-deoxyadenosine. Read More

    Phospho-Priming Confers Functionally Relevant Specificities for Rad53 Kinase Autophosphorylation.
    Biochemistry 2017 Sep 15. Epub 2017 Sep 15.
    Institute of Biological Chemistry, Academia Sinica , Taipei 115, Taiwan.
    The vast majority of in vitro structural and functional studies of the activation mechanism of protein kinases use the kinase domain alone. Well-demonstrated effects of regulatory domains or allosteric factors are scarce for serine/threonine kinases. Here we use a site-specifically phosphorylated SCD1-FHA1-kinase three-domain construct of the serine/threonine kinase Rad53 to show the effect of phospho-priming, an in vivo regulatory mechanism, on the autophosphorylation intermediate and specificity. Read More

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