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    68463 results match your criteria Biochemistry[Journal]

    1 OF 1370

    Ampulexins: A New Family of Peptides in Venom of the Emerald Jewel Wasp, Ampulex compressa.
    Biochemistry 2018 Jan 19. Epub 2018 Jan 19.
    The parasitoid wasp Ampulex compressa injects venom directly into the brain and subesophageal ganglion of the cockroach Periplaneta americana, inducing a seven to ten day lethargy termed hypokinesia. Hypokinesia presents as a significant reduction in both escape response and spontaneous walking. We examined aminergic and peptidergic components of milked venom with HPLC and MALDI-TOF mass spectrometry. Read More

    Structural and biophysical characterization of human EXTL3: domain organisation, glycosylation and solution structure.
    Biochemistry 2018 Jan 18. Epub 2018 Jan 18.
    Heparan sulfate proteoglycans are proteins substituted with one or more heparan sulfate (HS) polysaccharides, found in abundance at cell surfaces. HS chains influence the activity of many biologically important molecules involved in cellular communication and signaling. The exostosin (EXT) proteins are glycosyltransferases in the Golgi apparatus that assemble HS chains on HSPGs. Read More

    Efficient Fusion at Neutral pH by Human Immunodeficiency Virus gp41 Trimers containing the Fusion Peptide and Transmembrane Domain.
    Biochemistry 2018 Jan 18. Epub 2018 Jan 18.
    Human immunodeficiency virus (HIV) is membrane-enveloped and an initial infection step is joining/fusion of viral and cell membranes. This step is catalyzed by gp41 which is a single-pass integral viral membrane protein. The protein contains a ~170-residue ectodomain located outside the virus that is important for fusion, and includes the fusion peptide (FP), N-helix, loop, C-helix, and viral membrane-proximal external region (MPER). Read More

    Molecular mechanisms in the selectivity of non-steroidal anti-inflammatory drugs.
    Biochemistry 2018 Jan 18. Epub 2018 Jan 18.
    Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) 1 and 2 with varying degrees of selectivity. A group of COX-2 selective inhibitors - coxibs - bind in a time-dependent manner through a three-step mechanism, utilizing a side-pocket in the binding site. Coxibs have been extensively probed to identify the structural features regulating the slow tight-binding mechanism responsible for COX-2 selectivity. Read More

    Acetylation by Eis and Deacetylation by Rv1151c of Mycobacterium tuberculosis HupB: Biochemical and Structural Insight.
    Biochemistry 2018 Jan 18. Epub 2018 Jan 18.
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536-0596, United States.
    Bacterial nucleoid-associated proteins (NAPs) are critical to genome integrity and chromosome maintenance. Post-translational modifications of bacterial NAPs appear to function similarly to their better studied mammalian counterparts. The histone-like NAP HupB from Mycobacterium tuberculosis (Mtb) was previously observed to be acetylated by the acetyltransferase Eis, leading to genome reorganization. Read More

    Role of glycanation and convertase maturation of the soluble Glypican-3 in inhibiting proliferation of hepatocellular carcinoma cells.
    Biochemistry 2018 Jan 18. Epub 2018 Jan 18.
    Glypican 3 (GPC3) is a complex heparan sulfate proteoglycan associated with the outer surface of the plasma membrane by a glycosyl-phosphatidylinositol anchor (GPI). It is also N-glycosylated and processed by a furine-like convertase. GPC3 has numerous biological functions. Read More

    A small-molecule inhibitor of human DNA polymerase eta potentiates the effects of cisplatin in tumor cells.
    Biochemistry 2018 Jan 18. Epub 2018 Jan 18.
    Translesion DNA synthesis (TLS) performed by human DNA polymerase eta (hpol η) allows tolerance of damage from cis-diamminedichloroplatinum(II) (CDDP or cisplatin). We have developed hpol η inhibitors derived from N-aryl-substituted indole barbituric acid (IBA), indole thiobarbituric acid (ITBA), and indole quinuclidine scaffolds and identified 5-((5-chloro-1-(naphthalen-2-ylmethyl)-1H-indol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (PNR-7-02), an ITBA derivative that inhibited hpol η activity with an IC50 value of 8 μM and exhibited five- to ten-fold specificity for hpol η over replicative pols. We conclude from kinetic analyses, chemical footprinting assays, and molecular docking that PNR-7-02 binds to a site on the little finger domain and interferes with the proper orientation of template DNA to inhibit hpol η. Read More

    Prediction of Hot Spots at Myeloid Cell Leukemia-1-Inhibitors Interface using Energy Estimation and Alanine Scanning Mutagenesis.
    Biochemistry 2018 Jan 18. Epub 2018 Jan 18.
    Myeloid cell leukemia 1 (Mcl1) is an anti-apoptotic protein that plays central role in apoptosis regulation. Also, Mcl1 has the potency to resist apoptotic cues resulting in up-regulation and cancer cell protection. A molecular probe that has the potential to specifically target Mcl1, and thereby provoke its down-regulatory activity is very essential. Read More

    hOGG1 removes solution-accessible 8-oxoG lesions from globally-substituted nucleosomes except at the dyad region.
    Biochemistry 2018 Jan 17. Epub 2018 Jan 17.
    Persistent DNA damage is responsible for mutagenesis, aging, and disease. Repair of the prototypic oxidatively damaged guanine lesion 8-oxo-7,8-dihydroguanine (8-oxoG) is initiated by oxoguanine glycosylase (hOGG1 in humans). In this work, we examine hOGG1 activity on DNA packaged as it is in chromatin, in a nucleosome core particle (NCP). Read More

    Prediction of active site and distal residues in E. coli DNA polymerase III alpha polymerase activity.
    Biochemistry 2018 Jan 17. Epub 2018 Jan 17.
    The process of DNA replication is carried out with high efficiency and accuracy by DNA polymerases. The replicative polymerase in E. coli is DNA Pol III, which is a complex of 10 different subunits that coordinates simultaneous replication on the leading and lagging strands. Read More

    PokMT1 from the polyketomycin biosynthetic machinery of Streptomyces diastatochromogenes Tü6028 belongs to the emerging family of C-methyltransferases that act on CoA-activated aromatic substrates.
    Biochemistry 2018 Jan 17. Epub 2018 Jan 17.
    Recent biochemical characterizations of the MdpB2 CoA ligase and MdpB1 C-methyltransferase (C-MT) from the maduropeptin (MDP, 2) biosynthetic machinery revealed unusual pathway logic involving C-methylation occurring on a CoA-activated aromatic substrate. Here we confirmed this pathway logic for the biosynthesis of polyketomycin (POK, 3). Biochemical characterization unambiguously established that PokM3 and PokMT1 catalyze the sequential conversion of 6-methylsalicylic acid (6-MSA, 4) to form 3,6-dimethylsalicylyl-CoA (3,6-DMSA-CoA, 6), which serves as the direct precursor for the 3,6-dimethylsalicylic acid (3,6-DMSA) moiety in the biosynthesis of 3. Read More

    Designing Flavoprotein-GFP fusion Probes for Analyte-specific Ratiometric Fluorescence Imaging.
    Biochemistry 2018 Jan 17. Epub 2018 Jan 17.
    The development of genetically encoded fluorescent probes for analyte-specific imaging has revolutionized our understanding of intracellular processes. Current classes of intracellular probes depend on the selection of binding domains that either undergo conformational changes on analyte binding or can be linked to thiol redox chemistry. Here we have designed novel probes by fusing a flavoenzyme, whose fluorescence is quenched on reduction by the analyte of interest, with a GFP domain to allow for rapid and specific ratiometric sensing. Read More

    Analysis of Cellular Tyrosine Phosphorylation via Chemical Rescue of Conditionally Active Abl Kinase.
    Biochemistry 2018 Jan 17. Epub 2018 Jan 17.
    Identifying direct substrates targeted by protein kinases is important in understanding cellular physiology and intracellular signal transduction. Mass-spectrometry based quantitative proteomics provides a powerful tool for comprehensively characterizing the downstream substrates of protein kinases. This approach is efficiently applied to receptor kinases which can be precisely, directly, and rapidly activated by some agent, such as a growth factor. Read More

    A Dynamic Protein-Protein Coupling Between the TonB-dependent Transporter FhuA and TonB.
    Biochemistry 2018 Jan 17. Epub 2018 Jan 17.
    Bacterial outer membrane TonB-dependent transporters function by executing cycles of binding and unbinding to the inner membrane protein TonB. In the vitamin B12 transporter BtuB and the ferric citrate transporter FecA, substrate binding increases the periplasmic exposure of the Ton box, an energy-coupling segment. This increased exposure appears to enhance the affinity of the transporter for TonB. Read More

    Enzyme Architecture: The Role of a Flexible Loop in Activation of Glycerol-3-Phosphate Dehydrogenase for Catalysis of Hydride Transfer.
    Biochemistry 2018 Jan 16. Epub 2018 Jan 16.
    The side chain of Q295 of glycerol-3-phosphate dehydrogenase from human liver (hlGPDH) lies in a flexible loop. This loop folds over the phosphodianion of substrate dihydroxyacetone phosphate (DHAP), where Q295 interacts with the side chain cation from R269, which is ion-paired to the substrate phosphodianion. Kinetic parameters kcat/Km (M-1 s-1) and kcat/KGAKHPi (M-2 s-1) were determined, respectively, for catalysis of the reduction of DHAP and for dianion activation of catalysis of reduction of glycolaldeyde (GA) catalyzed by wildtype, Q295G, Q295S, Q295A, and Q295N mutants of hlGPDH. Read More

    Catalytic Mechanism of Cruzain from Trypanosoma cruzi as Determined from Solvent Kinetic Isotope Effects of Steady-State and Pre-Steady-State Kinetics.
    Biochemistry 2018 Jan 16. Epub 2018 Jan 16.
    Cruzain, an important drug target for Chagas disease, is a member of Clan CA of the cysteine proteases. Understanding the catalytic mechanism of cruzain is vital to the design of new inhibitors. To this end, we have performed pH-rate profiles for substrates and affinity agents, and have determined solvent kinetic isotope effects in pre-steady-state and steady-state modes using three substrates: Cbz-Phe-Arg-AMC, Cbz-Arg-Arg-AMC and Cbz-Arg-Ala-AMC. Read More

    Design of a "Mini" Nucleic Acid Probe for Cooperative Binding of an RNA-Repeated Transcript Associated with Myotonic Dystrophy Type 1.
    Biochemistry 2018 Jan 19. Epub 2018 Jan 19.
    Department of Chemistry, ‡Institute for Biomolecular Design and Discovery (IBD), and §CNAST, Carnegie Mellon University , 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, United States.
    Toxic RNAs containing expanded trinucleotide repeats are the cause of many neuromuscular disorders, one being myotonic dystrophy type 1 (DM1). DM1 is triggered by CTG-repeat expansion in the 3'-untranslated region of the DMPK gene, resulting in a toxic gain of RNA function through sequestration of MBNL1 protein, among others. Herein, we report the development of a relatively short miniPEG-γ peptide nucleic acid probe, two triplet repeats in length, containing terminal pyrene moieties, that is capable of binding rCUG repeats in a sequence-specific and selective manner. Read More

    Modulating the molybdenum coordination sphere of Escherichia coli trimethylamine N-oxide reductase.
    Biochemistry 2018 Jan 15. Epub 2018 Jan 15.
    The well-studied enterobacterium Escherichia coli present in the human gut is able to reduce TMAO to trimethylamine (TMA) during anaerobic respiration. The TMAO reductase TorA is a monomeric, bis-molybdopterin guanine dinucleotide (bis-MGD) cofactor-containing enzyme belonging to the dimethylsulfoxide (DMSO) reductase family of molybdoenzymes. We report on a system for the in vitro reconstitution of TorA with molybdenum cofactors (Moco) from different sources. Read More

    Characterization of an Hsp90-independent interaction between the co-chaperone p23 and the transcription factor p53.
    Biochemistry 2018 Jan 15. Epub 2018 Jan 15.
    The cancer-suppressing transcription factor p53 is regulated by a wide variety of cellular factors, including many chaperones. The DNA-binding domain (DBD) of p53 is known to interact with the chaperone Hsp90, but the role of other members of the chaperone network, including co-chaperones such as p23 is unknown. Using a combination of NMR titration, isothermal titration calorimetry, fluorescence anisotropy and native agarose gel electrophoresis, we have identified a direct interaction between the p53 DBD and the Hsp90 co-chaperone p23 that occurs in the absence of Hsp90. Read More

    Stabilizing leaf and branch compost cutinase (LCC) with glycosylation: Mechanism and effect on PET hydrolysis.
    Biochemistry 2018 Jan 12. Epub 2018 Jan 12.
    Cutinases are polyester hydrolases that show a remarkable capability to hydrolyze polyethylene terephthalate (PET) to its monomeric units. This revelation has stimulated research aimed at developing sustainable and green cutinase-catalyzed PET recycling methods. Leaf and branch compost cutinase (LCC) is particularly suited towards these ends given its relatively high PET hydrolysis activity and thermostability. Read More

    Proteomic Analysis of the Downstream Signaling Network of PARP1.
    Biochemistry 2018 Jan 19. Epub 2018 Jan 19.
    Department of Biochemistry, University of Texas Southwestern Medical Center , Dallas, Texas 75390, United States.
    Poly-ADP-ribosylation (PARylation) is a protein posttranslational modification (PTM) that is critically involved in many biological processes that are linked to cell stress responses. It is catalyzed by a class of enzymes known as poly-ADP-ribose polymerases (PARPs). In particular, PARP1 is a nuclear protein that is activated upon sensing nicked DNA. Read More

    Measuring RNA-Ligand Interactions with Microscale Thermophoresis.
    Biochemistry 2018 Jan 12. Epub 2018 Jan 12.
    In the past twenty years, there has been a dramatic increase in the study of RNA. RNA has gone from being known as an intermediate in the central dogma of molecular biology to a molecule with a large diversity of structure and function that is involved in all aspects of biology. As new functions are rapidly discovered, it has become clear that there is a need for RNA-targeting small molecule probes to investigate RNA biology and clarify the potential for therapeutics based on RNA/small molecule interactions. Read More

    Malaria Derived Glycosylphosphatidylinositol Anchor Enhances Anti-Pfs25 Functional Antibodies That Block Malaria Transmission.
    Biochemistry 2018 Jan 16. Epub 2018 Jan 16.
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Rockville, Maryland 20852, United States.
    Malaria, one of the most common vector borne human diseases, is a major world health issue. In 2015 alone, more than 200 million people were infected with malaria, out of which, 429 000 died. Even though artemisinin-based combination therapies (ACT) are highly effective at treating malaria infections, novel efforts toward development of vaccines to prevent transmission are still needed. Read More

    Functional Implications of Intracellular Phase Transitions.
    Biochemistry 2018 Jan 11. Epub 2018 Jan 11.
    Intracellular environments are heterogeneous milieus comprising of macromolecules, osmolytes, and a range of assemblies that include membrane-bound organelles and membraneless biomolecular condensates. The latter are non-stoichiometric assemblies of protein and RNA molecules. They represent distinct phases and form via intracellular phase transitions. Read More

    Increasing the Stability of Recombinant Human Green Cone Pigment.
    Biochemistry 2018 Jan 10. Epub 2018 Jan 10.
    Three types of cone cells exist in the human retina, each containing a different pigment responsible for the initial step of photo-transduction. These pigments are distinguished by their specific absorbance maxima, 425 nm (blue), 530 nm (green) and 560 nm (red). Each pigment contains a common chromophore, 11-cis-retinal covalently bound to an opsin protein via a Schiff base. Read More

    Structural Insight into the Discrimination between 8-oxoguanine Glycosidic Conformers by DNA Repair Enzymes: A Molecular Dynamics Study of hOgg1 and FPG.
    Biochemistry 2018 Jan 10. Epub 2018 Jan 10.
    hOgg1 and FPG are the primary DNA repair enzymes responsible for removing the major guanine oxidative product (G), namely 7,8-dihydro-8-oxoguanine (OG), in humans and bacteria, respectively. While natural G adopts the anti conformation and forms a Watson-Crick pair with cytosine (C), OG can also adopt the syn conformation and form a Hoogsteen pair with adenine (A). hOgg1 removes OG paired with C, but is inactive toward the OG:A pair. Read More

    Solution NMR Structure and Backbone Dynamics of the Partially Disordered Arabidopsis thaliana Phloem Protein 16-1, A Putative mRNA Transporter.
    Biochemistry 2018 Jan 10. Epub 2018 Jan 10.
    Although RNA-binding proteins in plant phloem are believed to carry out long-distance systemic transport of RNA in the phloem conduit, the structure of none of them is known. The Arabidopsis thaliana phloem protein 16-1 (AtPP16-1) is such a putative mRNA transporter whose structure and backbone dynamics have been studied at pH 4.1, 25oC, by high-resolution NMR spectroscopy. Read More

    Mechanistic Investigations of Lysine-Tryptophan Crosslink Formation Catalyzed by Streptococcal Radical SAM Enzymes.
    Biochemistry 2018 Jan 10. Epub 2018 Jan 10.
    Streptide is a ribosomally synthesized and post-translationally modified peptide with a unique cyclization motif consisting of an intramolecular lysine-tryptophan crosslink. Three radical SAM enzymes, StrB, AgaB, and SuiB from different Streptococci, have been shown to install this modification onto their respective precursor peptides in a leader-dependent fashion. Herein we conduct detailed investigations to differentiate between several plausible mechanistic proposals, specifically addressing radical versus electrophilic addition to the indole during crosslink formation, the role of substrate side-chains in binding in the enzyme active site, and the identity of the catalytic base in the reaction cycle. Read More

    Reaction Intermediates of Nitric Oxide Synthase from Deinococcus radiodurans as Revealed by Pulse Radiolysis; Evidence for Intramo-lecular Electron Transfer from Biopterin to FeII-O2 Complex.
    Biochemistry 2018 Jan 10. Epub 2018 Jan 10.
    Nitric oxide synthase (NOS) is a cytochrome P450-type mono-oxygenase that catalyzes the oxidation of L-arginine (Arg) to nitric oxide (NO) through a reaction intermediate N-hydroxy-L-arginine (NHA). The mechanism underlying the reaction catalyzed by NOS from Deinococcus radiodurans was investigated using pulse radiolysis. Radiolytically-generated hydrated electrons reduced the heme iron of NOS within 2 μs. Read More

    Human DNA repair genes possess potential G-quadruplex sequences in their promoters and 5`-untranslated regions.
    Biochemistry 2018 Jan 10. Epub 2018 Jan 10.
    The cellular response to oxidative stress includes transcriptional changes, particularly for genes involved in DNA repair. Recently, our laboratory demonstrated that oxidation of 2`-deoxyguanosine (G) to 8-oxo-7,8-dihydro-2`-deoxyguanosine (OG) in G-rich potential G-quadruplex sequences (PQSs) in gene promoters impacts the level of gene expression up or down depending on the position of the PQS in the promoter. In the present report, bioinformatic analysis found that the 390 human DNA repair genes in the genome ontology initiative harbor 2,936 PQSs in their promoters and 5`-untranslated regions (5`-UTRs). Read More

    Differential Response to Ca2+ from Vertebrate and Invertebrate Calumenin is Governed by a Single Amino Acid Residue.
    Biochemistry 2018 Jan 10. Epub 2018 Jan 10.
    Calumenin (Calu) is a well-conserved multi EF-hand containing Ca2+-binding protein. In this work, we focused our attention on the alterations that calumenin has undergone during evolution. We demonstrate that vertebrate calumenin is significantly different from its invertebrate homologs with respect to its response to Ca2+-binding. Read More

    X-ray structures of the proprotein convertase furin bound with substrate analog inhibitors reveal substrate specificity determinants beyond the S4 pocket.
    Biochemistry 2018 Jan 9. Epub 2018 Jan 9.
    The proprotein convertase (PC) furin is a highly specific serine protease modifying and thereby activating proteins in the secretory pathway by proteolytic cleavage. Its substrates are involved in many diseases including cancer and infections caused by bacteria and viruses. Understanding furin's substrate specificity is of crucial importance for the development of pharmacologically applicable inhibitors. Read More

    Epoxycyclohexenedione-type Compounds are a New Class of Inhibitors of the Bovine Mitochondrial ADP/ATP Carrier.
    Biochemistry 2018 Jan 9. Epub 2018 Jan 9.
    Through the extensive screening of our chemical library, we found epoxycyclohexenedione (ECHD)-type compounds (AMM-59 and -120) as unique inhibitors of the bovine heart mitochondrial ADP/ATP carrier (AAC). The present study investigated the mechanism of the inhibition of AAC by ECHDs using submitochondrial particles (SMPs). Proteomic analyses of ECHD-bound AAC as well as biochemical characterization using different SH-reagents showed that ECHDs inhibit the function of AAC by covalently binding primarily to Cys57 and secondarily to Cys160. Read More

    Design of small molecules that compete with nucleotide binding to an engineered oncogenic KRAS allele.
    Biochemistry 2018 Jan 9. Epub 2018 Jan 9.
    RAS mutations are found in 30% of all human cancers, with KRAS the most frequently mutated among the three RAS isoforms (KRAS, NRAS, HRAS). However, directly targeting oncogenic KRAS with small molecules in the nucleotide-binding site has been difficult due to the high affinity of KRAS for GDP and GTP. We designed an engineered allele of KRAS, and a covalent inhibitor that competes for GTP and GDP. Read More

    Glutathionylation inhibits catalytic activity of Arabidopsis β-amylase3 but not paralog β-amylase1.
    Biochemistry 2018 Jan 8. Epub 2018 Jan 8.
    β-amylase3 (BAM3) is an enzyme essential for starch degradation in plant leaves and is also transcriptionally-induced under cold stress. However, we recently reported that BAM3's enzymatic activity decreased in cold-stressed Arabidopsis leaves, although activity of BAM1, a homologous leaf β-amylase was largely unaffected. This decrease in BAM3 activity may relate to starch accumulation reported in cold-stressed plants. Read More

    Using Chemical Synthesis To Study and Apply Protein Glycosylation.
    Biochemistry 2018 Jan 16. Epub 2018 Jan 16.
    Department of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado , Boulder, Colorado 80303, United States.
    Protein glycosylation is one of the most common post-translational modifications and can influence many properties of proteins. Abnormal protein glycosylation can lead to protein malfunction and serious disease. While appreciation of glycosylation's importance is growing in the scientific community, especially in recent years, a lack of homogeneous glycoproteins with well-defined glycan structures has made it difficult to understand the correlation between the structure of glycoproteins and their properties at a quantitative level. Read More

    Structural, biochemical, and evolutionary characterization of glyoxylate/hydroxypyruvate reductases shows their division into two distinct subfamilies.
    Biochemistry 2018 Jan 8. Epub 2018 Jan 8.
    The D-2-hydroxyacid dehydrogenase (2HADH) family illustrates a complex evolutionary history with multiple lateral gene transfers, gene duplications, and losses. As a result, the exact functional annotation of individual members can be extrapolated to a very limited extent. Here, we revise the previous simplified view on the classification of the 2HADH family; specifically, we show that the previously delineated glyoxylate/hydroxypyruvate reductase (GHPR) subfamily consists of two evolutionary separated GHRA and GHRB subfamilies. Read More

    Structural and kinetic studies of Asp632 mutants and fully-reduced NADPH-cytochrome P450 oxidoreductase define the role of Asp632 loop dynamics in control of NADPH binding and hydride transfer.
    Biochemistry 2018 Jan 8. Epub 2018 Jan 8.
    Conformational changes of NADPH-cytochrome P450 oxidoreductase (CYPOR) associated with electron transfer from NADPH to electron acceptors via FAD and FMN have been investigated through structural studies of the 4-electron-reduced NADP+-bound enzyme and kinetic and structural studies of mutants affecting the conformation of the mobile Gly631-Asn635 loop (Asp632 loop). The structure of 4-electron-reduced, NADP+-bound wild type CYPOR shows the plane of the nicotinamide ring positioned perpendicular to the FAD isoalloxazine with its carboxamide group forming H-bonds with N1 of the flavin ring and the Thr535 hydroxyl group. In the reduced enzyme, the C8-C8 atoms of the two flavin rings are ~1 Å closer compared to the fully oxidized and 1-electron-reduced structures, which suggests that flavin reduction facilitates interflavin electron transfer. Read More

    In Aqua Veritas: The Indispensable yet Mostly Ignored Role of Water in Phase Separation and Membrane-less Organelles.
    Biochemistry 2018 Jan 19. Epub 2018 Jan 19.
    Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida , Tampa, Florida 33612, United States.
    Despite the common practice of presenting structures of biological molecules on an empty background and the assumption that interactions between biological macromolecules take place within the inert solvent, water represents an active component of various biological processes. This Perspective addresses indispensable, yet mostly ignored, roles of water in biological liquid-liquid phase transitions and in the biogenesis of various proteinaceous membrane-less organelles. We point out that changes in the structure of water reflected in the changes in its abilities to donate and/or accept hydrogen bonds and participate in dipole-dipole and dipole-induced dipole interactions in the presence of various solutes (ranging from small molecules to synthetic polymers and biological macromolecules) might represent a driving force for the liquid-liquid phase separation, define partitioning of various solutes in formed phases, and define the exceptional ability of intrinsically disordered proteins to be engaged in the formation of proteinaceous membrane-less organelles. Read More

    Cluster Dependent Charge-Transfer Dynamics in Iron-Sulfur Proteins.
    Biochemistry 2018 Jan 5. Epub 2018 Jan 5.
    Photo-induced charge-transfer dynamics and the influence of cluster size on the dynamics were investigated using five iron-sulfur clusters: the 1Fe-4S cluster in Pyrococcos furiosus rubredoxin, the 2Fe-2S cluster in Pseudomonas putida putidaredoxin, the 4Fe-4S cluster in nitrogenase iron protein, and the 8Fe-7S P-cluster and the 7Fe-9S-1Mo FeMo cofactor in nitrogenase MoFe protein. Laser excitation promotes the iron-sulfur clusters to excited electronic states that relax to lower states. The electronic relaxation lifetimes of the 1Fe-4S, the 8Fe-7S, and the 7Fe-9S-1Mo clusters are in the picoseconds timescale, although the dynamics of the MoFe protein is a mixture of the dynamics of the later two clusters. Read More

    Inactivation of 4-Oxalocrotonate Tautomerase by 5-Halo-2-hydroxy-2,4-pentadienoates.
    Biochemistry 2018 Jan 5. Epub 2018 Jan 5.
    5-Halo-2-hydroxy-2,4-pentadienoates (5-halo-HPDs) are reportedly generated in the bacterial catabolism of halogenated aromatic hydrocarbons by the meta-fission pathway. The 5-halo-HPDs, where the halogen can be bromide, chloride, or fluoride, result in the irreversible inactivation of 4-oxalocrotonate tautomerase (4-OT), which precedes the enzyme that generates them. The loss of activity is due to the covalent modification of the nucleophilic amino-terminal proline. Read More

    We FRET so You Don't Have To: New Models of the Lipoprotein Lipase Dimer.
    Biochemistry 2018 Jan 5;57(2):241-254. Epub 2018 Jan 5.
    Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
    Lipoprotein lipase (LPL) is a dimeric enzyme that is responsible for clearing triglyceride-rich lipoproteins from the blood. Although LPL plays a key role in cardiovascular health, an experimentally derived three-dimensional structure has not been determined. Such a structure would aid in understanding mutations in LPL that cause familial LPL deficiency in patients and help in the development of therapeutic strategies to target LPL. Read More

    Disrupted hydrogen bond network and impaired ATPase activity in an Hsc70 cysteine mutant.
    Biochemistry 2018 Jan 4. Epub 2018 Jan 4.
    The ATPase domain of the 70-kD heat shock protein (Hsp70) family members shows a high degree of sequence, structural, and functional homology across species. A broadly conserved residue within the Hsp70 ATPase domain that captured our attention is an unpaired cysteine, positioned proximal to the site of nucleotide binding. Prior studies of several Hsp70 family members show this cysteine is not required for Hsp70 ATPase activity, yet select amino acid replacements of the cysteine can dramatically alter ATP hydrolysis. Read More

    Enhanced Solubilization of Class B Radical S-adenosylmethionine Methylases by Improved Cobalamin Uptake in Escherichia coli.
    Biochemistry 2018 Jan 3. Epub 2018 Jan 3.
    The methylation of unactivated carbon and phosphorus centers is a burgeoning area of biological chemistry, especially given that such reactions constitute key steps in the biosynthesis of numerous enzyme cofactors, antibiotics, and other natural products of clinical value. These kinetically challenging reactions are catalyzed exclusively by enzymes in the radical S-adenosylmethionine (SAM) superfamily and have been grouped into four classes: A, B, C, and D. Class B radical SAM (RS) methylases require a cobalamin cofactor in addition to the [4Fe-¬4S] cluster that is characteristic of RS enzymes. Read More

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