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Enzyme like activity

Hongbo Guo, Huib Rabouw, Anne Slomp, Meiling Dai, Floor van der Vegt, Jan W M van Lent, Ryan McBride, James C Paulson, Raoul J de Groot, Frank J M van Kuppeveld, Erik de Vries, Cornelis A M de Haan
Interactions of influenza A virus (IAV) with sialic acid (SIA) receptors determine viral fitness and host tropism. Binding to mucus decoy receptors and receptors on epithelial host cells is determined by a receptor-binding hemagglutinin (HA), a receptor-destroying neuraminidase (NA) and a complex in vivo receptor-repertoire. The crucial but poorly understood dynamics of these multivalent virus-receptor interactions cannot be properly analyzed using equilibrium binding models and endpoint binding assays. In this study, the use of biolayer interferometric analysis revealed the virtually irreversible nature of IAV binding to surfaces coated with synthetic sialosides or engineered sialoglycoproteins in the absence of NA activity...
August 13, 2018: PLoS Pathogens
Kyle J Messina, Philip C Bevilacqua
The number of self-cleaving small ribozymes has increased sharply in recent years. Advances have been made in describing these ribozymes in terms of four catalytic strategies: α describes in-line attack, β describes neutralization of the nonbridging oxygens, γ describes activation of the nucleophile, and δ describes stabilization of the leaving group. Current literature presents the rapid self-cleavage of the twister ribozyme in terms of all four of these classic catalytic strategies. Herein, we describe the nonspecific contribution of small molecules to ribozyme catalysis...
August 13, 2018: Journal of the American Chemical Society
Ryuta Morihara, Toru Yamashita, Xia Liu, Yumiko Nakano, Yusuke Fukui, Kota Sato, Yasuyuki Ohta, Nozomi Hishikawa, Jingwei Shang, Koji Abe
Sigma-1 receptor (Sig-1R) is expressed at endoplasmic reticulum (ER) membranes, where it regulates a variety of specific physiological functions. However, the profile and exact roles of ER stress-related molecules after Sig-1R agonist treatment in an in vivo stroke model are largely unknown. The aim of this study is to investigate the effect of a novel Sig-1R agonist, aniline derivative compound (Comp-AD), on the ER stress response following ischemic stroke. Male C57BL/6J mice received transient middle cerebral artery occlusion for 90 min, and were then treated with vehicle saline or Comp-AD at reperfusion...
August 13, 2018: Journal of Neuroscience Research
Chaoqun Sun, Zili Huang, Li Liu, Menglu Li, Huzhi Zheng
In this work, umbelliferone, a kind of coumarin derivative, was proved to exhibit peroxidase-like activity that could catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide to generate a blue-colored oxide (oxTMB). The catalytic mechanism is similar to that of native enzymes (e.g. horseradish peroxidase, HRP) and nanozymes, which follow the Michaelis-Menten kinetics behavior. Meanwhile, the 7-hydroxyl group of umbelliferone plays a significant role in the peroxidase-like activity...
2018: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
A L F V Assumpção, Z Lu, K W Marlowe, K S Shaffer, X Pan
Canine diffuse large B-cell lymphoma (DLBCL), the most common hematologic malignancy of dogs, is associated with poor overall survival. The lack of conventional chemotherapies with sustainable efficacy warrants investigation of novel therapies. Pevonedistat (MLN4924) is a potent and selective small molecule NEDD8-activating enzyme inhibitor. In human activated B-cell-like (ABC) diffuse large B-cell lymphoma, pevonedistat induces lymphoma cell apoptosis, DNA damage and G1 cell cycle arrest by inhibiting the nuclear factor-κB (NF-κB) pathway...
August 13, 2018: Veterinary and Comparative Oncology
Neil Venardos, Xin-Sheng Deng, Quinzhou Yao, Michael J Weyant, T Brett Reece, Xianzhong Meng, David A Fullerton
BACKGROUND: Calcific aortic stenosis is a chronic inflammatory disease. Proinflammatory stimulation via toll-like receptor 4 (TLR4) causes the aortic valve interstitial cell (AVIC) to undergo phenotypic change. The AVIC first assumes an inflammatory phenotype characterized by the production of inflammatory mediators such as intercellular adhesion molecule-1 (ICAM-1), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1). This change has been linked with an osteogenic phenotypic response...
October 2018: Journal of Surgical Research
Juan Manuel Castro, Virginia Angélica Bianchi, Mariano Martín Pascual, César Almeida, Andrés Venturino, Carlos Marcelo Luquet
Immune cell characterization, immunological response and the associated gill oxidative balance were studied in the Patagonian freshwater mussel, Diplodon chilensis, using two microbiological immunostimulant models: Saccharomyces cerevisiae and Escherichia coli. Mussels were collected out of the breeding season in Paimún Lake and acclimated in the laboratory. Two exposure experiments were performed during two consecutive weeks: (1) mussels challenged with 500 yeast cells mL-1 ; and (2) mussels challenged with 1000 bacteria cells mL-1 ...
August 9, 2018: Journal of Invertebrate Pathology
Kunisi S Venkatasubban, Joseph L Johnson, Jamie L Thomas, Abdul Fauq, Bernadette Cusack, Terrone L Rosenberry
Carbamates are esters of substituted carbamic acids that react with acetylcholinesterase (AChE) by initially transferring the carbamoyl group to a serine residue in the enzyme active site accompanied by loss of the carbamate leaving group followed by hydrolysis of the carbamoyl enzyme. This hydrolysis, or decarbamoylation, is relatively slow, and half-lives of carbamoylated AChEs range from 4 min to more than 30 days. Therefore, carbamates are effective AChE inhibitors that have been developed as insecticides and as therapeutic agents...
August 9, 2018: Archives of Biochemistry and Biophysics
István Hajdú, József Kardos, Balázs Major, Gabriella Fabó, Zsolt Lőrincz, Sándor Cseh, György Dormán
Lysyl oxidase (LOX) enzymes as potential drug targets maintain constant attention in the therapy of fibrosis, cancer and metastasis. In order to measure the inhibitory activity of small molecules on the LOX enzyme family members a fluorometric activity screening method was developed. During assay validation, previously reported non-selective small inhibitor molecules (BAPN, MCP-1, thiram, disulfiram) were investigated on all of the major LOX enzymes. We confirmed that MCP-1, thiram, disulfiram are in fact pan-inhibitors, while BAPN inhibits only LOX-like enzymes (preferably LOX-like-protein-2, LOXL2) in contrast to the previous reports...
July 6, 2018: Bioorganic & Medicinal Chemistry Letters
Yan He, Yang Wang, Yingxia Hu, Haobo Jiang
Melanization is a universal defense mechanism of insects against microbial infection. During this response, phenoloxidase (PO) is activated from its precursor by prophenoloxidase activating protease (PAP), the terminal enzyme of a serine protease (SP) cascade. In the tobacco hornworm Manduca sexta, hemolymph protease-14 (HP14) is autoactivated from proHP14 to initiate the protease cascade after host proteins recognize invading pathogens. HP14, HP21, proHP1*, HP6, HP8, PAP1-3, and non-catalytic serine protease homologs (SPH1 and SPH2) constitute a portion of the extracellular SP-SPH system to mediate melanization and other immune responses...
August 8, 2018: Insect Biochemistry and Molecular Biology
Kristina Haeussler, Karin Fritz-Wolf, Max Reichmann, Stefan Rahlfs, Katja Becker
The enzyme 6-phosphogluconate dehydrogenase (6PGD) of the malaria parasite Plasmodium falciparum catalyzes the third step of the pentose phosphate pathway (PPP) converting 6-phosphogluconate (6PG) to ribulose 5-phosphate. The NADPH produced by 6PGD is crucial for antioxidant defense and redox regulation and ribose 5-phosphate is essential for DNA and RNA synthesis in the rapidly growing parasite. Thus, 6PGD represents an attractive antimalarial drug target. In this study, we present the X-ray structures of Pf6PGD in native form as well as in complex with 6PG or NADP+ at resolutions of 2...
August 8, 2018: Journal of Molecular Biology
Albert van der Vliet, Yvonne M W Janssen-Heininger, Vikas Anathy
The lung is a delicate organ with a large surface area that is continuously exposed to the external environment, and is therefore highly vulnerable to exogenous sources of oxidative stress. In addition, each of its approximately 40 cell types can also generate reactive oxygen species (ROS), as byproducts of cellular metabolism and in a more regulated manner by NOX enzymes with functions in host defense, immune regulation, and cell proliferation or differentiation. To effectively regulate the biological actions of exogenous and endogenous ROS, various enzymatic and non-enzymatic antioxidant defense systems are present in all lung cell types to provide adequate protection against their injurious effects and to allow for appropriate ROS-mediated biological signaling...
August 8, 2018: Molecular Aspects of Medicine
Mareike Bütepage, Sarah Krieg, Laura Eckei, Jinyu Li, Giulia Rossetti, Patricia Verheugd, Bernhard Lüscher
Mono-ADP-ribosylation is a posttranslational modification, which is catalyzed in cells by certain members of the ADP-ribosyltransferase diphtheria toxin-like family (ARTD) of ADP-ribosyltransferases (aka PARP enzymes). It involves the transfer of a single residue of ADP-ribose (ADPr) from the cofactor NAD+ onto substrate proteins. Although 12 of the 17 members of the ARTD family have been defined as mono-ARTDs in in vitro assays, relatively little is known about their exact cellular functions. A major challenge is the detection of mono-ADP-ribosylated (MARylated) proteins in cells as no antibodies are available that detect exclusively MARylated proteins...
2018: Methods in Molecular Biology
Bijoy Chellan, Elizabeth Rojas, Chunling Zhang, Marion A Hofmann Bowman
Enzyme modified non-oxidative LDL (ELDL) is effectively taken up by vascular smooth muscle cells (SMC) and mediates transition into foam cells and produces phenotypic changes in SMC function. Our data show that incubation of human coronary artery SMC (HCASMC) with low concentration of ELDL (10 μg/ml) results in significantly enhanced foam cell formation compared to oxidized LDL (200 μg/ml; p < 0.01) or native LDL (200 μg/ml; p < 0.01). Bioinformatic network analysis identified activation of p38 MAPK, NFkB, ERK as top canonical pathways relevant for biological processes linked to cell migration and osteoblastic differentiation in ELDL-treated cells...
August 10, 2018: Scientific Reports
Gurpreet Kaur, Pratap Kumar Pati
BACKGROUND: NADPH oxidase (Nox) is a critical enzyme involved in the generation of apoplastic superoxide (O2 - ), a type of reactive oxygen species (ROS) and hence regulate a wide range of biological functions in many organisms. Plant Noxes are the homologs of the catalytic subunit from mammalian NADPH oxidases and are known as respiratory burst oxidase homologs (Rbohs). Previous studies have highlighted their versatile roles in tackling different kind of stresses and in plant growth and development...
August 10, 2018: BMC Plant Biology
Md Tarikul Islam, Suprovath Kumar Sarker, Shezote Talukder, Golam Sarower Bhuyan, Asifuzzaman Rahat, Nafisa Nawal Islam, Hasan Mahmud, Mohammad Amir Hossain, A K M Muraduzzaman, Jakia Rahman, Syeda Kashfi Qadri, Mohammod Shahidullah, Mohammad Abdul Mannan, Sarabon Tahura, Manzoor Hussain, Narayan Saha, Shahida Akhter, Nazmun Nahar, Firoza Begum, Tahmina Shirin, Sharif Akhteruzzaman, Syed Saleheen Qadri, Firdausi Qadri, Kaiissar Mannoor
BACKGROUND: Like glucose-6-phosphate dehydrogenase (G6PD) deficient hemizygous males and homozygous females, heterozygous females could also manifest hemolytic crisis, neonatal hyperbilirubinemia or kernicterus upon exposure to oxidative stress induced by certain foods such as fava beans, drugs or infections. Although hemizygous males and homozygous females are easily detected by conventional G6PD enzyme assay method, the heterozygous state could be missed by the conventional methods as the mosaic population of both normal and deficient RBCs circulates in the blood...
August 10, 2018: BMC Genetics
Shailee V Tiwari, Nawaz S Sharif, Rekha I Gajare, Julio A Seijas Vazquez, Jaiprakash N Sangshetti, Manoj D Damale, Anna Pratima G Nikalje
The work reports the facile synthesis of novel α-aminophosphonate derivatives coupled with indole-2,3-dione moieties, namely the diethyl(substituted phenyl/heteroaryl)(2-(2-oxoindolin-3-ylidene)hydrazinyl)methylphosphonates derivatives 4 ( a ⁻ n ). One-pot three component Kabachnik-Fields reactions were used to synthesize these derivatives. The reaction was carried out at room temperature by stirring in presence of ceric ammonium nitrate (CAN) as a green catalyst. The structures of the synthesized compounds were established by spectral studies...
August 8, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Min-Kyung Kang, Eun-Jung Lee, Yun-Ho Kim, Dong Yeon Kim, Hyeongjoo Oh, Soo-Il Kim, Young-Hee Kang
Diabetes-associated visual cycle impairment has been implicated in diabetic retinopathy, and chronic hyperglycemia causes detrimental effects on visual function. Chrysin, a naturally occurring flavonoid found in various herbs, has anti-inflammatory, antioxidant, and neuroprotective properties. The goal of the current study was to identify the retinoprotective role of chrysin in maintaining robust retinoid visual cycle-related components. The in vitro study employed human retinal pigment epithelial (RPE) cells exposed to 33 mM of glucose or advanced glycation end products (AGEs) in the presence of 1⁻20 μM chrysin for three days...
August 8, 2018: Nutrients
Laura Giusti, Cristina Angeloni, Maria Cristina Barbalace, Serena Lacerenza, Federica Ciregia, Maurizio Ronci, Andrea Urbani, Clementina Manera, Maria Digiacomo, Marco Macchia, Maria Rosa Mazzoni, Antonio Lucacchini, Silvana Hrelia
Neurodegenerative diseases represent a heterogeneous group of disorders that share common features like abnormal protein aggregation, perturbed Ca2+ homeostasis, excitotoxicity, impairment of mitochondrial functions, apoptosis, inflammation, and oxidative stress. Despite recent advances in the research of biomarkers, early diagnosis, and pharmacotherapy, there are no treatments that can halt the progression of these age-associated neurodegenerative diseases. Numerous epidemiological studies indicate that long-term intake of a Mediterranean diet, characterized by a high consumption of extra virgin olive oil, correlates with better cognition in aged populations...
August 8, 2018: International Journal of Molecular Sciences
Vance G Nielsen, Nathaniel Frank, Ryan W Matika
Geographic isolation and other factors result in evolution-driven diversity of the enzymatic composition of venom of pit vipers in the same genus. The present investigation sought to characterize venoms obtained from such genetically diverse Ovophis and Trimeresurus pit vipers utilizing thrombelastographic coagulation kinetic analyses. The coagulation kinetics of human plasma were assessed after exposure to venom obtained from two Ovophis and three Trimeresurus species. The potency of each venom was defined (µg/mL required to equivalently change coagulation); additionally, venoms were exposed to carbon monoxide (CO) or a metheme-inducing agent to modulate any enzyme-associated heme...
August 8, 2018: Toxins
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