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171.
Golin J Kon ZN Wu CP Martello J Hanson L Supernavage S Ambudkar SV Sauna ZE 《Biochemistry》2007,46(45):13109-13119
The yeast Pdr5p transporter is a 160 kDa protein that effluxes a large variety of xenobiotic compounds. In this study, we characterize its ATPase activity and demonstrate that it has biochemical features reminiscent of those of other ATP-binding cassette multidrug transporters: a relatively high Km for ATP (1.9 mM), inhibition by orthovanadate, and the ability to specifically bind an azidoATP analogue at the nucleotide-binding domains. Pdr5p-specific ATPase activity shows complete, concentration-dependent inhibition by clotrimazole, which is also known to be a potent transport substrate. Our results indicate, however, that this inhibition is noncompetitive and caused by the interaction of clotrimazole with the transporter at a site that is distinct from the ATP-binding domains. Curiously, Pdr5p-mediated transport of clotrimazole continues at intracellular concentrations of substrate that should eliminate all ATPase activity. Significantly, however, we observed that the Pdr5p has GTPase and UTPase activities that are relatively resistant to clotrimazole. Furthermore, the Km(GTPase) roughly matches the intracellular concentrations of the nucleotide reported for yeast. Using purified plasma membrane vesicles, we demonstrate that Pdr5p can use GTP to fuel substrate transport. We propose that Pdr5p increases its multidrug transport substrate specificity by using more than one nucleotide as an energy source. 相似文献
172.
Biftu T Feng D Qian X Liang GB Kieczykowski G Eiermann G He H Leiting B Lyons K Petrov A Sinha-Roy R Zhang B Scapin G Patel S Gao YD Singh S Wu J Zhang X Thornberry NA Weber AE 《Bioorganic & medicinal chemistry letters》2007,17(1):49-52
Replacement of the triazolopiperazine ring of sitagliptin (DPP-4 IC(50)=18nM) with 3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one gave dipeptidyl peptidase IV (DPP-4) inhibitor 1 which is potent (DPP-4 IC(50)=2.6nM), selective, and efficacious in an oral glucose tolerance test in mice. It was selected for extensive preclinical development as a potential back-up candidate to sitagliptin. 相似文献
173.
Biotechnological conversion of agro-industrial wastewaters into biodegradable plastic, poly beta-hydroxybutyrate 总被引:1,自引:0,他引:1
Khardenavis AA Suresh Kumar M Mudliar SN Chakrabarti T 《Bioresource technology》2007,98(18):3579-3584
Waste activated sludge generated from a combined dairy and food processing industry wastewater treatment plant was evaluated for its potential to produce biodegradable plastic, poly beta-hydroxybutyric acid (PHB). Deproteinized jowar grain-based distillery spentwash yielded 42.3% PHB production (w/w), followed by filtered rice grain-based distillery spentwash (40% PHB) when used as substrates. Addition of di-ammonium hydrogen phosphate (DAHP) resulted in an increase in PHB production to 67% when raw rice grain-based spentwash was used. Same wastewater, after removal of suspended solids by filtration and with DAHP supplementation resulted in lower PHB production (57.9%). However, supplementing other wastes with DAHP led to a substantial decrease in PHB content in comparison to what was observed in the absence of DAHP. 相似文献
174.
Biftu T Scapin G Singh S Feng D Becker JW Eiermann G He H Lyons K Patel S Petrov A Sinha-Roy R Zhang B Wu J Zhang X Doss GA Thornberry NA Weber AE 《Bioorganic & medicinal chemistry letters》2007,17(12):3384-3387
Molecular modeling was used to design a rigid analog of sitagliptin 1. The X-ray crystal structure of sitagliptin bound to DPP-4 suggested that the central beta-amino butyl amide moiety could be replaced with a cyclohexylamine group. This was confirmed by structural analysis and the resulting analog 2a was synthesized and found to be a potent DPP-4 inhibitor (IC(50)=21 nM) with excellent in vivo activity and pharmacokinetic profile. 相似文献
175.
The requirement of sterol glucoside for pexophagy in yeast is dependent on the species and nature of peroxisome inducers 下载免费PDF全文
Nazarko TY Polupanov AS Manjithaya RR Subramani S Sibirny AA 《Molecular biology of the cell》2007,18(1):106-118
Sterol glucosyltransferase, Ugt51/Atg26, is essential for both micropexophagy and macropexophagy of methanol-induced peroxisomes in Pichia pastoris. However, the role of this protein in pexophagy in other yeast remained unclear. We show that oleate- and amine-induced peroxisomes in Yarrowia lipolytica are degraded by Atg26-independent macropexophagy. Surprisingly, Atg26 was also not essential for macropexophagy of oleate- and amine-induced peroxisomes in P. pastoris, suggesting that the function of sterol glucoside (SG) in pexophagy is both species and peroxisome inducer specific. However, the rates of degradation of oleate- and amine-induced peroxisomes in P. pastoris were reduced in the absence of SG, indicating that P. pastoris specifically uses sterol conversion by Atg26 to enhance selective degradation of peroxisomes. However, methanol-induced peroxisomes apparently have lost the redundant ability to be degraded without SG. We also show that the P. pastoris Vac8 armadillo repeat protein is not essential for macropexophagy of methanol-, oleate-, or amine-induced peroxisomes, which makes PpVac8 the first known protein required for the micropexophagy, but not for the macropexophagy, machinery. The uniqueness of Atg26 and Vac8 functions under different pexophagy conditions demonstrates that not only pexophagy inducers, such as glucose or ethanol, but also the inducers of peroxisomes, such as methanol, oleate, or primary amines, determine the requirements for subsequent pexophagy in yeast. 相似文献
176.
177.
Stensvold CR Suresh GK Tan KS Thompson RC Traub RJ Viscogliosi E Yoshikawa H Clark CG 《Trends in parasitology》2007,23(3):93-96
Blastocystis is a ubiquitous enteric protistan parasite that has extensive genetic diversity and infects humans and many other animals. Distinct molecular methodologies developed to detect variation and obtain information about transmission patterns and clinical importance have resulted in a confusing array of terminologies for the identification and designation of Blastocystis subtypes. In this article, we propose a standardization of Blastocystis terminology to improve communication and correlate research results. Based primarily on published small-subunit ribosomal RNA gene analyses, we propose that all mammalian and avian isolates should be designated Blastocystis sp. and assigned to one of nine subtypes. 相似文献
178.
The purpose of this research was to study whether the bioavailability of lovastatin could be improved by administering lovastatin
solid lipid nanoparticles (SLN) duodenally to rats. Lovastatin SLN were developed using triglycerides by hot homogenization
followed by ultrasonication. Particle size and zeta potential were measured by photon correlation spectroscopy. The solid
state of the drug in the SLN and lipid modification were characterized. Bioavailability studies were conducted in male Wistar
rats after intraduodenal administration of lovastatin suspension and SLN. Stable lovastatin SLN having a mean size range of
60 to 119 nm and a zeta potential range of −16 to −21 mV were developed. More than 99% of the lovastatin was entrapped in
the SLN. Lovastatin was dispersed in an amorphous state, and triglycerides were in {ieE162-1} form in the SLN. In vitro stability
studies showed the slow release and stability of lovastatin SLN. The relative bioavailabilities of lovastatin and lovastatin
hydroxy acid of SLN were increased by ∼173% and 324%, respectively, compared with the reference lovastatin suspension.
Published: March 23, 2007 相似文献
179.
Paul Prajita Patel Paritosh Verma Suresh K. Mishra Pragyan Sahu Bikash R. Panda Pritam Kumar Kushwaha Gajraj Singh Senapati Shantibhusan Misra Namrata Suar Mrutyunjay 《Cell biology and toxicology》2022,38(1):111-127
Cell Biology and Toxicology - The key to bacterial virulence relies on an exquisite balance of signals between microbe and hosts. Bacterial toxin–antitoxin (TA) system is known to play a... 相似文献
180.