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991.
Garcia Collazo AM Koehler KF Garg N Färnegårdh M Husman B Ye L Ljunggren J Mellström K Sandberg J Grynfarb M Ahola H Malm J 《Bioorganic & medicinal chemistry letters》2006,16(5):1240-1244
Based on the examination of the crystal structure of rat TRbeta complexed with 3,5,3'-triiodo-l-thyronine (2) a novel TRbeta-selective indole derivative 6b was prepared and tested in vitro. This compound was found to be 14 times selective for TRbeta over TRalpha in binding and its beta-selectivity could be rationalized through the comparison of the X-ray crystallographic structures of 6b complexed with TRalpha and TRbeta. 相似文献
992.
Michaux C Muccioli GG Lambert DM Wouters J 《Bioorganic & medicinal chemistry letters》2006,16(18):4772-4776
Substituted (thio)hydantoins (2-thioxoimidazolidinones and imidazolidinediones) were reported as new potential reversible inhibitors of fatty acid amide hydrolase (FAAH). Their binding mode to FAAH was explored to rationalize their activity and give idea to design highly active inhibitors. Starting from the crystal structure of one of these molecules, docking studies provide us with rational basis for the design of new inhibitors within the thiohydantoin family. 相似文献
993.
Manjasetty BA Büssow K Fieber-Erdmann M Roske Y Gobom J Scheich C Götz F Niesen FH Heinemann U 《Protein science : a publication of the Protein Society》2006,15(4):914-920
The human protein PTD012 is the longer product of an alternatively spliced gene and was described to be localized in the nucleus. The X-ray structure analysis at 1.7 A resolution of PTD012 through SAD phasing reveals a monomeric protein and a novel fold. The shorter splice form was also studied and appears to be unfolded and non-functional. The structure of PTD012 displays an alphabetabetaalpha four-layer topology. A metal ion residing between the central beta-sheets is partially coordinated by three histidine residues. X-ray absorption near-edge structure (XANES) analysis identifies the PTD012-bound ion as Zn(2+). Tetrahedral coordination of the ion is completed by the carboxylate oxygen atom of an acetate molecule taken up from the crystallization buffer. The binding of Zn(2+) to PTD012 is reminiscent of zinc-containing enzymes such as carboxypeptidase, carbonic anhydrase, and beta-lactamase. Biochemical assays failed to demonstrate any of these enzyme activities in PTD012. However, PTD012 exhibits ester hydrolase activity on the substrate p-nitrophenyl acetate. 相似文献
994.
Schauvliege S Narine K Bouchez S Desmet D Van Parys V Van Nooten G Gasthuys F 《Laboratory animals》2006,40(4):341-352
The feasibility of an anaesthetic protocol developed for surgery during right heart bypass in sheep is reported. Seven female Suffolk sheep, weighing 25-35 kg, were selected for the study. Premedication consisted of midazolam and methadone (both 0.1 mg kg(-1) intravenously). Anaesthesia was induced with propofol (2-4 mg kg(-1)) and maintained with isoflurane in oxygen and continuous rate infusions of propofol (5-7 mg kg(-1 )h(-1)) and fentanyl (5 microg kg(-1) bolus, 5 microg kg(-1) h(-1)). Cisatracurium (0.2 mg kg(-1)) provided muscle relaxation. A standard roller pump was used for the extracorporeal circulation. Drugs administered to maintain blood pressure and heart rate within acceptable levels included phenylephrine (3-4 microg kg(-1)), ephedrine (0.1-0.2 mg kg(-1)), nitroglycerine (50-150 microg kg(-1) h(-1)) and metoprolol succinate (30-80 microg kg(-1)). Electrolytes were infused as needed. Postoperative analgesia was provided by an intercostal block (15 mL 0.5% bupivacaine + epinephrine), carprofen (4 mg kg(-1)) and an opioid (methadone 0.1 mg kg(-1) or buprenorphine 0.01 mg kg(-1)). One sheep became hypoxic during the bypass (PaO(2) 47.7 mmHg). Irregularities of the electrocardiogram were observed during manipulation of the heart in all animals. During the initial phase of the bypass, blood pressure decreased in all sheep, accompanied by dilatation of the heart and large intrathoracic veins in five sheep. With appropriate treatment, blood pressure was restored and easily maintained until the end of the bypass. Weaning from the bypass, using an infusion of nitrates, was smooth. One sheep required a blood transfusion because of severe blood loss and another sheep died postoperatively from respiratory complications. Minor irregularities of the electrocardiogram observed during manipulation of the heart were not life threatening and required no treatment. Decreases in blood pressure at the beginning of the bypass can be expected and require treatment. Nitrates are useful in avoiding volume overload during weaning. The anaesthetic protocol is acceptable for surgery under right heart bypass in sheep. 相似文献
995.
996.
de Ruyck J Durisotti V Oudjama Y Wouters J 《The Journal of biological chemistry》2006,281(26):17864-17869
Isopentenyl-diphosphate (IPP):dimethylallyl diphosphate isomerase is a key enzyme in the biosynthesis of isoprenoids. The mechanism of the isomerization reaction involves protonation of the unactivated carbon-carbon double bond in the substrate, but identity of the acidic moiety providing the proton is still not clear. Multiple sequence alignments and geometrical features observed in crystal structures of complexes with IPP isomerase suggest that Tyr-104 could play an important role during catalysis. A series of mutants was constructed by directed mutagenesis and characterized by enzymology. Crystallographic and thermal denaturation data for Y104A and Y104F mutants were obtained. Those data demonstrate the importance of residue Tyr-104 for proper folding of Escherichia coli type I IPP isomerase. 相似文献
997.
Nick Barker Meritxell Huch Pekka Kujala Marc van de Wetering Hugo J. Snippert Johan H. van Es Toshiro Sato Daniel E. Stange Harry Begthel Maaike van den Born Esther Danenberg Stieneke van den Brink Jeroen Korving Arie Abo Peter J. Peters Nick Wright Richard Poulsom Hans Clevers 《Cell Stem Cell》2010,6(1):25-36
998.
999.
The technologies associated with DNA sequencing are rapidly evolving. Indeed, single-molecule DNA sequencing strategies are cheaper and faster than ever before. Despite this progress, every sequencing platform to date relies on reading the genome in small, abstract fragments, typically of less than 1000 bases in length. The overarching aim of the optical map is to complement the information derived from DNA sequencing by providing long-range context on which these short sequence reads can be built. This is typically done using an enzyme to target and modify at short DNA sequences of, say, six bases in length throughout the genome. By accurately placing these short pieces of sequence on long genomic DNA fragments, up to several millions of bases in length, a scaffold for sequence assembly can be obtained. This review focuses on three enzymatic approaches to optical mapping. Optical mapping was first developed using restriction enzymes to sequence-specifically cleave DNA that is immobilized on a surface. More recently, nicking enzymes have found application in the sequence-specific fluorescent labeling of DNA for optical mapping. Such covalent modification allows the DNA to be imaged in solution, and this, in combination with developing nanofluidic technologies, is enabling new high-throughput approaches to mapping. And, finally, this review will discuss the recent development of mapping with subdiffraction-limit precision using methyltransferase enzymes to label the DNA with an ultrahigh density. 相似文献
1000.
The completion of the genome project for Naegleria gruberi provides a unique insight into the metabolic capacities of an organism, for which there is an almost complete lack of experimental data. The metabolism of Naegleria seems to be extremely versatile, as can be expected for a free-living amoeboflagellate, but although considered to be fully aerobic, its genome also predicts important anaerobic traits. Other predictions are that carbohydrates are oxidised to carbon dioxide and water when oxygen is not limiting and that in the absence of oxygen the end-products will be succinate, acetate and minor quantities of ethanol and d-lactate. The hybrid mitochondrion/hydrogenosome has both cytochromes and an [Fe] hydrogenase, but seems to lack pyruvate-ferredoxin oxidoreductase. Genomic information also provides the possibility to identify drugs with a possible mode of action in the fatal primary amoebic meningoencephalitis caused by the closely related opportunistic pathogen Naegleria fowleri. 相似文献