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Andrea Fagagnini, Riccardo Montioli, Andra Caloiu, Marc Ribó, Douglas V Laurents, Giovanni Gotte
Bovine pancreatic ribonuclease A (RNase A) is the monomeric prototype of the so-called secretory 'pancreatic-type' RNase super-family. Like the naturally domain-swapped dimeric bovine seminal variant, BS-RNase, and its glycosylated RNase B isoform, RNase A forms N- and C-terminal 3D domain-swapped oligomers after lyophilization from acid solutions, or if subjected to thermal denaturation at high protein concentration. All mentioned RNases can undergo deamidation at Asn67, forming Asp or isoAsp derivatives that modify the protein net charge and consequently its enzymatic activity...
October 23, 2016: Biochimica et Biophysica Acta
Mayte Conejero-Muriel, Isaac Rodriguez-Ruiz, Cristobal Verdugo-Escamilla, Andreu Llobera, Jose Antonio Gavira
Microfluidics or lab-on-a-chip technology offer clear advantages over conventional systems such as a dramatic reduction of reagent consumption or a shorter analysis time, which are translated into costs effective systems. In this work, we present a photonic enzymatic lab on a chip reactor based on Cross-Linked Enzyme Crystals (CLECs), able to work in continuous flow, as a highly sensitive, robust, reusable and stable platform for continuous sensing with superior performance as compared to the state of the art...
October 26, 2016: Analytical Chemistry
Heinrich Taegtmeyer, Truong Lam, Giovanni Davogustto
The heart is a biological pump that converts chemical to mechanical energy. This process of energy conversion is highly regulated to the extent that energy substrate metabolism matches energy use for contraction on a beat-to-beat basis. The biochemistry of cardiac metabolism includes the biochemistry of energy transfer, metabolic regulation, and transcriptional, translational as well as posttranslational control of enzymatic activities. Pathways of energy substrate metabolism in the heart are complex and dynamic, but all of them conform to the First Law of Thermodynamics...
September 15, 2016: Comprehensive Physiology
Thierry Lioux, Marc-Antoine Mauny, Alain Lamoureux, Nicolas Bascoul, Mathieu Hays, Fabienne Vernejoul, Anne-Sophie Baudru, Cédric Boularan, Justine Lopes-Vicente, Gregory Qushair, Gérard Tiraby
We describe novel STING-activating cyclic dinucleotides whose constituent nucleosides are adenosine and inosine, and that vary by ribose substitution, internucleotide linkage position and phosphate modification. In mammalian cells in vitro, some of these cAIMP analogs induce greater STING-dependent IRF and NF-κB pathway signaling than do the reference agonists for murine (DMXAA) or human (2',3'-cGAMP) STING. In human blood ex vivo, they induce type I interferons (IFNs) and pro-inflammatory cytokines: for the former, 3',3'-cAIMP (9; EC50: 6...
October 26, 2016: Journal of Medicinal Chemistry
Jeong Eun Hyeon, Sang Kyu Shin, Sung Ok Han
The utilization of scaffolds for enzyme immobilization involves advanced bionanotechnology applications in biorefinery fields, which can be achieved by optimizing the function of various enzymes. This review presents various current scaffolding techniques based on proteins, microbes and nanomaterials for enzyme immobilization, as well as the impact of these techniques on the biorefinery of lignocellulosic materials. Among them, architectural scaffolds have applied to useful strategies for protein engineering to improve the performance of immobilized enzymes in several industrial and research fields...
October 26, 2016: Biotechnology Journal
Michail Nomikos, Angelos Thanassoulas, Konrad Beck, Maria Theodoridou, Jasmine Kew, Junaid Kashir, Brian L Calver, Emily Matthews, Pierre Rizkallah, Zili Sideratou, George Nounesis, Anthony F Lai
Hereditary leukonychia is a rare genetic nail disorder characterized by distinctive whitening of the nail plate of all twenty nails. Hereditary leukonychia may exist as an isolated feature, or in simultaneous occurrence with other cutaneous or systemic pathologies. Associations between hereditary leukonychia and mutations in the gene encoding phospholipase C delta-1 (PLCδ1) have previously been identified. However, the molecular mechanisms underlying PLCδ1-mutations and hereditary leukonychia remain uncharacterized...
October 26, 2016: FEBS Journal
Zeineb Kamoun, Alya Sellami Kamoun, Ali Bougatef, Rim Marrakchi Kharrat, Houssem Youssfi, Tahia Boudawara, Mouna Chakroun, Moncef Nasri, Najiba Zeghal
Ethanol consumption-induced oxidative stress that is a major etiological factor has been proven to play important roles in organs' injury. In the present study, we investigated the protective effect of fish protein hydrolysate prepared from the heads and viscera of sardinelle (Sardinella aurita) (SPH) against the toxicity of ethanol on the liver and kidney of adult male rats. Animals were divided into four groups of six animals each: group C served as control, group Eth received 30 % ethanol solution at the dose of 3 g/kg body weight, group SPH received only 7...
October 25, 2016: Environmental Science and Pollution Research International
Mohammad Abass Ahanger, R M Agarwal
Pot experiments were conducted to find out the effectivity of K on Triticum aestivum L cultivars. Polyethylene glycol 6000 (PEG 6000) was used as an osmoticum to induce osmotic stress under sand culture setting up the water potential of external solution at -3 and -5 bars. In pots, plants were raised under restricted and normal irrigation and K was applied in varying doses (0, 20, 40, 60 kg ha(-1)) and estimation of different physiological and biochemical parameters was done at two developmental stages, i...
October 25, 2016: Protoplasma
Wynton C McClary, John Paul Sumida, Michele Scian, Lorela Paco, William M Atkins
Cytochrome P4503A4 (CYP3A4) is a peripheral membrane protein that plays a major role in enzymatic detoxication of many drugs and toxins. CYP3A4 has an integral membrane N-terminal helix and a localized patch comprised of the G'- and F'-helix regions that are embedded in the membrane, but the effects of membrane composition on CYP3A4 function are unknown. Here, circular dichroism and differential scanning calorimetry were used to compare the stability of CYP3A4 in lipid bilayer nanodiscs with varying ratios of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC): 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)...
October 26, 2016: Biochemistry
Berhane Ghebrehiwet, Allen P Kaplan, Kusumam Joseph, Ellinor I B Peerschke
The blood plasma contains four biologically important proteolytic cascades, which probably evolved from the same ancestral gene. This in part may explain why each cascade has very similar "initiating trigger" followed by sequential and cascade-like downstream enzymatic activation pattern. The four cascades are: the complement system, the blood clotting cascade, the fibrinolytic system, and the kallikrein-kinin system. Although much has been written about the interplay between all these enzymatic cascades, the cross-talk between the complement and the kinin generating systems has become particularly relevant as this interaction results in the generation of nascent molecules that have significant impact in various inflammatory diseases including angioedema and cancer...
November 2016: Immunological Reviews
Anna Erdei, Noémi Sándor, Bernadett Mácsik-Valent, Szilvia Lukácsi, Mariann Kremlitzka, Zsuzsa Bajtay
The complement system is a major component of immune defense. Activation of the complement cascade by foreign substances and altered self-structures may lead to the elimination of the activating agent, and during the enzymatic cascade, several biologically active fragments are generated. Most immune regulatory effects of complement are mediated by the activation products of C3, the central component. The indispensable role of C3 in opsonic phagocytosis as well as in the regulation of humoral immune response is known for long, while the involvement of complement in T-cell biology have been revealed in the past few years...
November 2016: Immunological Reviews
József Dobó, Gábor Pál, László Cervenak, Péter Gál
Mannose-binding lectin (MBL)-associated serine proteases (MASPs) are the enzymatic constituents of the lectin pathway of the complement system. They are complexed with large pattern recognition molecules (PRMs) such as MBL, other collectins, and ficolins. The main function of two of the three MASPs has crystallized lately: MASP-1 autoactivates first, then it activates MASP-2, and finally both participate in the formation of the C4b2a convertase. In addition to this, both enzymes are involved in several other processes which are subject to intense research nowadays...
November 2016: Immunological Reviews
David P Hickey, Krysti L Knoche, Kelan Albertson, Carolina Castro, Ross D Milton, Shelley D Minteer
Here, we demonstrate the use of phospholipid micelles to enhance O2 concentrations by two-fold at the surface of a bilirubin oxidase biocathode. Specifically, 1,2-diarachidoyl-sn-glycero-3-phosphocholine was used in a glucose enzymatic fuel cell to limit power losses due to O2 transport, even in a quiescent solution.
October 26, 2016: Chemical Communications: Chem Comm
Zhen Zhang, Dongmei Zhao, Yang Dai, Maosheng Cheng, Meiyu Geng, Jingkang Shen, Yuchi Ma, Jing Ai, Bing Xiong
Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a new series of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazole derivatives as potent FGFR inhibitors. The compound 6-(2,6-dichloro-3,5-dimethoxyphenyl)-N-phenyl-1H-indazole-4-carboxamide (10a) was identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that 6-(2,6-dichloro-3,5-dimethoxyphenyl)-N-(3-(4-methylpiperazin-1-yl)phenyl)-1H-indazole-4-carboxamide (13a) is the most potent FGFR1 inhibitor in this series, with an enzyme inhibitory activity IC50 value of about 30...
October 23, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Theodora Karamanidou, Vassilis Bourganis, Olga Kammona, Costas Kiparissides
Biopharmaceutics have been recognized as the drugs of choice for the treatment of several diseases, mainly due to their high selectivity and potent action. Nonetheless, their oral administration is a rather challenging problem, since their bioavailability is significantly hindered by various physiological barriers along the GI tract, including their acid-induced hydrolysis in the stomach, their enzymatic degradation throughout the GI tract and their poor mucosa permeability. Lipid-based nanocarriers represent a viable means for enhancing the oral bioavailability of biomolecules while diminishing toxicity-related issues...
October 26, 2016: Nanomedicine
Saket Kumar Singh, Bibhas Kumar Bhunia, Nandana Bhardwaj, Sween Gilotra, Biman B Mandal
Tunable repeated drug administration is often inevitable in number of pathological cases. Reloadable 3D matrices for sustained drug delivery are predicted as a prospective avenue to realize this objective. This study was directed towards sonication-induced fabrication of novel reloadable Bombyx mori silk fibroin (SF) (4, 6 and 8 wt%) hydrogel, injected within 3D porous (8 wt%) scaffolds. The focus was to develop a dual-barrier reloadable depot system for sustained molecular cargo-release. Both the varying SF concentration (4, 6 and 8 wt%) and the sonication time (30, 45 and 60 s) dictated the extent of cross-linking, β-sheet content and porosity (1-10 µm) influencing the release behavior of model molecules...
October 26, 2016: Molecular Pharmaceutics
Ikuo Kurisaki, Masataka Nagaoka
Thrombin is a serine protease involved in blood coagulation reaction and shows maximum enzymatic activity under the presence of Na(+). It has been supposed that Na(+)-binding promotes conversion from inactive form, whose primary substrate pocket (S1-pocket) collapse, to active form with properly formed S1-pocket. However, the evidences supporting this activation mechanism were derived from X-ray crystallographic structures solved under non-physiological conditions and by using thrombin mutants so that it still remains elusive whether the activation mechanism actually is attributed to Na(+)-binding...
October 26, 2016: Journal of Physical Chemistry. B
Daohui Zhao, Jian Zhou
The α-chymotrypsin (α-ChT) enzyme is extensively used for studying nanomaterial-induced enzymatic activity inhibition. A recent experimental study reported that carboxylized carbon nanotubes (CNTs) played an important role in regulating the α-ChT activity. In this study, parallel tempering Monte Carlo and molecular dynamics simulations were combined to elucidate the interactions between α-ChT and CNTs in relation to the CNT functional group density. The simulation results indicate that the adsorption and the driving force of α-ChT on different CNTs are contingent on the carboxyl density...
October 26, 2016: Physical Chemistry Chemical Physics: PCCP
Se Hyeon Park, Feilicia Soetyono, Hyung Kwoun Kim
Lysine decarboxylase (CadA) converts L-lysine into cadaverine (1,5-pentanediamin), which is an important platform chemical with many industrial applications. Although there have been many efforts to produce cadaverine through the soluble CadA enzyme or Escherichia coli whole cells overexpressing the CadA enzyme, there have been few reports concerning the immobilization of the CadA enzyme. Here, we have prepared a cross-linked enzyme aggregate (CLEA) of E. coli CadA and performed bioconversion using CadA(CLEA)...
October 25, 2016: Journal of Microbiology and Biotechnology
Woo Soo Jeong, Dong Ho Seo, Jong Hyun Jung, Dong Hyun Jung, Dong-Woo Lee, Young-Seo Park, Cheonseok Park
A highly thermostable β-(1-4)-glucanase (NA23_08975) gene (fig) from Fervidobacterium islandicum AW-1, a native-feather degrading thermophilic eubacterium, was cloned and expressed in Escherichia coli. The recombinant FiG (rFiG) protein showed strong activity toward β-D-glucan from barley (367.0 IU/mg), galactomannan (174.0 IU/mg), and 4-nitrophenyl-cellobioside (pNPC, 66.1 IU/mg), but relatively weak activity was observed with hydroxyethyl cellulose (HEC, 5.3 IU/mg), carboxymethyl cellulose (CMC, 2.4 IU/mg), and xylan from oat spelt (1...
October 25, 2016: Journal of Microbiology and Biotechnology
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