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https://www.readbyqxmd.com/read/28324835/flexible-biological-arsenite-oxidation-utilizing-nox-and-o2-as-alternative-electron-acceptors
#1
Jie Wang, Junfeng Wan, Zihao Wu, Hongli Li, Haisong Li, Christophe Dagot, Yan Wang
The feasibility of flexible microbial arsenite (As(III)) oxidation coupled with the reduction of different electron acceptors was investigated. The results indicated the acclimated microorganisms could oxidize As(III) with oxygen, nitrate and nitrite as the alternative electron acceptors. A series of batch tests were conducted to measure the kinetic parameters of As(III) oxidation and to evaluate the effects of environmental conditions including pH and temperature on the activity of biological As(III) oxidation dependent on different electron acceptors...
March 18, 2017: Chemosphere
https://www.readbyqxmd.com/read/28319395/spreading-kinetics-of-ultra-thin-liquid-films-using-molecular-dynamics
#2
Brooklyn Ann Noble, C Mathew Mate, Bart Raeymaekers
Ultra-thin liquid films play a critical role in numerous engineering applications. Although crucial to the design and application of ultra-thin liquid films, the physical mechanisms that govern spreading on the molecular scale are not well-understood, and disagreement among experiments, simulations, and theory remains. We use molecular dynamics simulations to quantify the speed at which the edge of a polymer droplet advances on a flat substrate as a function of various environmental and design parameters. We explain the physical mechanisms that drive and inhibit spreading, identify different spreading regimes, and clarify transitions between spreading regimes...
March 20, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28319184/streptococcus-suis-sortase-a-is-ca2-independent-and-is-inhibited-by-acteoside-isoquercitrin-and-baicalin
#3
Fuguang Chen, Fang Xie, Baoling Yang, Chengcheng Wang, Siguo Liu, Yueling Zhang
Sortase A (SrtA) has long been recognized as an ideal drug target for therapeutic agents against Gram-positive pathogens. However, the SrtA of Streptococcus suis (Ss-SrtA), an important zoonotic agent, has not been studied. In this study, the enzymatic properties of Ss-SrtA were investigated, and inhibition of Ss-SrtA by natural products was evaluated. Ss-SrtA was expressed and purified. The purified recombinant Ss-SrtA had maximal activity at pH 6.0-7.5, 45°C, and showed a Km of 6.7 μM for the hydrolysis of substrate abz-LPATG-dnp...
2017: PloS One
https://www.readbyqxmd.com/read/28318878/insulin-stimulates-transport-of-organic-anion-compounds-mediated-by-organic-anion-transporting-polypeptide-2b1-in-the-human-intestinal-cell-line-caco-2
#4
Taku Kobayashi, Takahiro Koizumi, Masaki Kobayashi, Jiro Ogura, Yuichi Horiuchi, Yuki Kimura, Ayuko Kondo, Ayako Furugen, Katsuya Narumi, Natsuko Takahashi, Ken Iseki
Organic anion transporting polypeptide 2B1 (OATP2B1) is the major uptake transporter in the intestine, and transports various clinically used therapeutic agents. Insulin acts through the insulin receptor in targeted cells, and Rab8A is one of the insulin signaling pathways. The small intestine in humans also expresses insulin receptor and Rab8A. It has been reported that insulin stimulates peptide transporter 1 (PEPT1) expression at the apical membrane and increases uptake of PEPT1 substrates in small intestine epithelial model cells (Caco-2 cells)...
December 27, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28318362/carbonic-anhydrase-inhibitors-modify-intracellular-ph-transients-and-contractions-of-rat-middle-cerebral-arteries-during-co2-hco3-fluctuations
#5
Jacob K Rasmussen, Ebbe Boedtkjer
The CO2/HCO3(-) buffer minimizes pH changes in response to acid-base loads, HCO3(-) provides substrate for Na(+),HCO3(-)-cotransporters and Cl(-)/HCO3(-)-exchangers, and H(+) and HCO3(-) modify vasomotor responses during acid-base disturbances. We show here that rat middle cerebral arteries express cytosolic, mitochondrial, extracellular, and secreted carbonic anhydrase isoforms that catalyze equilibration of the CO2/HCO3(-) buffer. Switching from CO2/HCO3(-)-free to CO2/HCO3(-)-containing extracellular solution results in initial intracellular acidification due to hydration of CO2 followed by gradual alkalinization due to cellular HCO3(-) uptake...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28318265/cytoskeletal-like-filaments-of-camkii-are-formed-in-a-regulated-and-zn2-dependent-manner
#6
Laurel Hoffman, Lin Li, Emil Alexov, Hugo Sanabria, Melvin Neal Waxham
Ca2+-Calmodulin-dependent protein kinase II (CaMKII) is highly abundant in neurons, where its concentration reaches that typically found for cytoskeletal proteins. Functional reasons for such a high concentration are not known, but given the multitude of known binding partners for CaMKII, a role as a scaffolding molecule has been proposed. In this report, we provide experimental evidence that demonstrates a novel structural role for CaMKII. We discovered that CaMKII forms filaments that can extend for several microns in the presence of certain divalent cations (Zn2+, Cd2+ and Cu2+) but not with others (Ca2+, Mg2+, Co2+ and Ni2+)...
March 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/28318037/deoxycytidine-and-deoxythymidine-treatment-for-thymidine-kinase-2-deficiency
#7
Carlos Lopez-Gomez, Rebecca J Levy, Maria J Sanchez-Quintero, Marti Juanola-Falgarona, Emanuele Barca, Beatriz Garcia-Diaz, Saba Tadesse, Caterina Garone, Michio Hirano
OBJECTIVE: Thymidine kinase 2 (TK2), a critical enzyme in the mitochondrial pyrimidine salvage pathway, is essential for mitochondrial DNA (mtDNA) maintenance. Mutations in the nuclear gene TK2 cause TK2 deficiency, which manifests predominantly in children as myopathy with mtDNA depletion. Molecular bypass therapy with the TK2 products, dCMP and dTMP, prolongs the lifespan of Tk2-deficient (Tk2(-/-) ) mice by 2-3 fold. Because we observed rapid catabolism of the deoxynucleoside monophosphates to deoxythymidine (dT) and deoxycytidine (dC), we hypothesized that: 1) deoxynucleosides might be the major active agents and 2) inhibition of deoxycytidine deamination might enhance dTMP+dCMP therapy...
March 20, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28317451/inclusion-of-saccharina-latissima-in-conventional-anaerobic-digestion-systems
#8
F Ometto, A Berg, A Björn, L Safaric, B H Svensson, A Karlsson, J Ejlertsson
Loading macroalgae into existing anaerobic digestion (AD) plants allows us to overcome challenges such as low digestion efficiencies, trace elements limitation, excessive salinity levels and accumulation of volatile fatty acids (VFAs), observed while digesting algae as a single substrate. In this work, the co-digestion of the brown macroalgae Saccharina latissima with mixed municipal wastewater sludge (WWS) was investigated in mesophilic and thermophilic conditions. The hydraulic retention time (HRT) and the organic loading rate (OLR) were fixed at 19 days and 2...
March 18, 2017: Environmental Technology
https://www.readbyqxmd.com/read/28317028/mycobacterial-caseinolytic-protease-gene-regulator-clgr-is-a-substrate-of-caseinolytic-protease
#9
Yoshiyuki Yamada, Thomas Dick
The mycobacterial caseinolytic protease ClpP1P2 is a degradative protease that recently gained interest as a genetically and pharmacologically validated drug target for tuberculosis. The first whole-cell active ClpP1P2 inhibitor, the human proteasome inhibitor bortezomib, is currently undergoing lead optimization to introduce selectivity for the bacterial target. How inhibition of ClpP1P2 translates into whole-cell antimicrobial activity is little understood. Previous work has shown that the caseinolytic protease gene regulator ClgR is an activator of the clpP1P2 genes and also suggested that this transcription factor may be a substrate of the protease...
March 2017: MSphere
https://www.readbyqxmd.com/read/28316141/dasatinib-inhibits-actin-fiber-reorganization-and-promotes-endothelial-cell-permeability-through-rhoa-rock-pathway
#10
Swapan K Dasgupta, Anhquyen Le, K Vinod Vijayan, Perumal Thiagarajan
Treatment with dasatinib, a tyrosine kinase inhibitor, is associated with edema, pleural effusion, and pulmonary edema. We investigated the effect of dasatinib on the barrier function of human microvascular endothelial cells-1 (HMEC-1) in vitro and in vivo. The permeability of HMEC-1 to fluorescein isothiocyante (FITC)-dextran increased in Transwell chambers within 5 min following the addition of therapeutic concentrations of dasatinib. The change in permeability was associated with increased activation of RhoA GTPase and its effector Rho-associated coiled-coil kinase 1(ROCK1)...
March 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28316073/arrhythmic-effects-of-epac-mediated-ryanodine-receptor-activation-in-langendorff-perfused-murine-hearts-are-associated-with-reduced-conduction-velocity
#11
Mengye Li, Sandeep Hothi, Samantha C Salvage, Kamalan Jeevaratnam, Andrew A Grace, Christopher L-H Huang
Recent papers have attributed arrhythmic substrate in murine RyR2-P2328S hearts to reduced action potential (AP) conduction velocities (CV), reflecting acute functional inhibition and/or reduced expression of sodium channels. We explored for acute effects of direct Epac (exchange protein directly activated by cAMP)-mediated ryanodine receptor-2 (RyR2) activation on arrhythmic substrate and CV. Monophasic action potential recordings demonstrated that initial steady (8-Hz) extrinsic pacing elicited ventricular tachycardia (VT) in 0 of 18 Langendorff-perfused wild-type mouse ventricles before pharmacological intervention...
March 18, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28316020/%C3%AE-hydroxybutyrate-boosts-mitochondrial-and-neuronal-metabolism-but-is-not-preferred-over-glucose-under-activated-conditions
#12
Lavanya B Achanta, Benjamin D Rowlands, Donald S Thomas, Gary D Housley, Caroline D Rae
The ketone body, β-hydroxybutyrate (βOHB), is metabolised by the brain alongside the mandatory brain fuel glucose. To examine the extent and circumstances by which βOHB can supplement glucose metabolism, we studied guinea pig cortical brain slices using increasing concentrations of [U-(13)C]D-βOHB in conjunction with [1-(13)C]D-glucose under conditions of normo- and hypoglycaemia, as well as under high potassium (40 mmol/L K(+)) depolarization in normo- and hypoglycaemic conditions. The contribution of βOHB to synthesis of GABA was also probed by inhibiting the synthesis of glutamine, a GABA precursor, with methionine sulfoximine (MSO)...
March 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28315686/crystal-structure-of-the-catalytic-domain-of-clostridium-perfringens-neuraminidase-in-complex-with-a-non-carbohydrate-based-inhibitor-2-cyclohexylamino-ethanesulfonic-acid
#13
Youngjin Lee, Hyung-Seop Youn, Jung-Gyu Lee, Jun Yop An, Kyoung Ryoung Park, Jung Youn Kang, Young Bae Ryu, Mi Sun Jin, Ki Hun Park, Soo Hyun Eom
Anti-bacterial and anti-viral neuraminidase agents inhibit neuraminidase activity catalyzing the hydrolysis of terminal N-acetylneuraminic acid (Neu5Ac) from glycoconjugates and help to prevent the host pathogenesis that lead to fatal infectious diseases including influenza, bacteremia, sepsis, and cholera. Emerging antibiotic and drug resistances to commonly used anti-neuraminidase agents such as oseltamivir (Tamiflu) and zanamivir (Relenza) have highlighted the need to develop new anti-neuraminidase drugs...
March 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28315663/enhancing-the-catalytic-deamination-activity-of-apobec3c-is-insufficient-to-inhibit-vif-deficient-hiv-1
#14
Ananda Ayyappan Jaguva Vasudevan, Henning Hofmann, Dieter Willbold, Dieter Häussinger, Bernd W Koenig, Carsten Münk
The retroviral restriction factors of the APOBEC3 (A3) cytidine deaminase family catalyze the deamination of cytidines in single-stranded viral DNA. APOBEC3C (A3C) is a strong antiviral factor against viral infectivity factor (vif)-deficient simian immunodeficiency (SIV) Δvif, however, a weak inhibitor against human immunodeficiency virus (HIV)-1 for reasons unknown. The precise link between the antiretroviral effect of A3C and its catalytic activity is incompletely understood. Here we show that the S61P mutation in human A3C (A3C...
March 15, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28315445/evaluation-of-pept1-transport-of-food-derived-antihypertensive-peptides-ile-pro-pro-and-leu-lys-pro-using-in-vitro-ex-vivo-and-in-vivo-transport-models
#15
John P Gleeson, David J Brayden, Sinéad M Ryan
Ile-Pro-Pro (IPP) and Leu-Lys-Pro (LKP) are food-derived antihypertensive peptides which inhibit angiotensin-converting enzyme (ACE) and may have potential to attenuate hypertension. There is debate over their mechanism of uptake across small intestinal epithelia, but paracellular and PepT1 carrier-mediated uptake are thought to be important routes. The aim of this study was to determine their routes of intestinal permeability using in vitro, ex vivo and in vivo intestinal models. The presence of an apical side pH of 6...
March 14, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28315351/-3-h-bmt-046091-a-potent-and-selective-radioligand-to-determine-aak1-distribution-and-target-engagement
#16
Justin V Louis, Yifeng Lu, Rick Pieschl, Yung Tian, Yang Hong, Kumaran Dandapani, Sreenivasulu Naidu, Reeba K Vikramadithyan, Carolyn Dzierba, Sarat Kumar Sarvasiddhi, Susheel J Nara, Joanne Bronson, John E Macor, Charlie Albright, Walter Kostich, Yu-Wen Li
Adaptor-associated kinase 1 (AAK1), a member of the Ark1/Prk1 family of serine/threonine kinases, plays a role in modulating clatherin coated endocytosis of specific surface receptors. We have demonstrated that AAK1 inhibitors are efficacious in rodent models of neuropathic pain (Kostich et al., 2016). Here we have characterized the binding properties and distribution pattern of the tritiated AAK1 radioligand, [(3)H]BMT-046091, in rodents and cynomolgus monkeys, and used the radioligand to measure the brain target occupancy following systemic administration of AAK1 inhibitors...
March 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28315327/discovery-of-a-kelch-like-ech-associated-protein-1-inhibitory-tetrapeptide-and-its-structural-characterization
#17
Satoshi Sogabe, Kotaro Sakamoto, Yusuke Kamada, Akito Kadotani, Yasunori Fukuda, Jun-Ichi Sakamoto
Keap1 constitutively binds to the transcription factor Nrf2 to promote its degradation, resulting in negative modulation of genes involved in cellular protection against oxidative stress. Keap1 is increasingly recognized as an attractive target for treating diseases involving oxidative stress, including cancer, atherosclerosis, diabetes, arthritis, and neurodegeneration. We used phage-display peptide screening to identify a tetrapeptide showing moderate binding affinity, which inhibits the interaction between Nrf2 and Keap1...
March 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28314825/increased-plasma-exposures-of-conjugated-metabolites-of-morinidazole-in-renal-failure-patients-a-critical-role-of-uremic-toxins
#18
Fandi Kong, Xiaoyan Pang, Kan Zhong, Zitao Guo, Xiuli Li, Dafang Zhong, Xiaoyan Chen
Morinidazole is a 5-nitroimidazole drug. Its sulfate conjugate M7 was a sensitive substrate of organic anion transporter 1 (OAT1) and OAT3, whereas N+-glucuronides M8-1 and M8-2 were only OAT3 substrates. In chronic renal failure (CRF) patients, plasma exposures of the three conjugates increased by 15-fold, which were also found in 5/6 nephrectomized (5/6 Nx) rats in this study. Although the transcriptions of Oat1 and Oat3 in 5/6 Nx rat kidneys decreased by 50%, no difference was observed on the three conjugate uptakes between control and 5/6 Nx rat kidney slices...
March 17, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28306627/novel-microspheres-reduce-the-formation-of-deep-venous-thrombosis-and-repair-the-vascular-wall-in-a-rat-model
#19
Bingyang Dai, Lan Li, Qiangqiang Li, Xiaoxiao Song, Dongyang Chen, Jin Dai, Yao Yao, Wenjin Yan, Huajian Teng, Fang Yang, Zhihong Xu, Qing Jiang
L-Arginine (L-arg), widely known as a substrate for endogenous nitric oxide synthesis, can improve endothelial function associated with the vasculature, inhibit platelet aggregation, and alter the activity of vascular smooth muscle cells. P-selectin is a membrane component of the platelet alpha-granule and the endothelial cell-specific Wiebel-Palade body that plays a central role in mediating interactions between platelets and both leukocytes and the endothelium. The experiment was designed to evaluate the effect of novel microspheres with L-arg targeting P-selectin on the formation of deep vein thrombosis and repair of vascular wall in a rat model...
March 16, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28304114/antiviral-and-cytostatic-evaluation-of-5-1-halo-2-sulfonylvinyl-and-5-2-furyl-uracil-nucleosides
#20
Zhiwei Wen, Sazzad H Suzol, Jufang Peng, Yong Liang, Robert Snoeck, Graciela Andrei, Sandra Liekens, Stanislaw F Wnuk
Transition metal-catalyzed halosulfonylation of 5-ethynyl uracil nucleosides provided (E)-5-(1-chloro-2-tosylvinyl)uridines. Tetrabutylammonium fluoride-mediated direct CH arylation of 5-iodouracil nucleosides with furan or 2-heptylfuran gave 5-furyl-substituted nucleosides without the necessity of using the organometallic substrates. These two classes of 5-substituted uracil nucleosides as well their corresponding ester derivatives were tested against a broad range of DNA and RNA viruses and the human immunodeficiency virus (HIV)...
March 17, 2017: Archiv der Pharmazie
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