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11.
Goring DR Banks P Fallis L Baszczynski CL Beversdorf WD Rothstein SJ 《The Plant journal : for cell and molecular biology》1992,2(6):999-1003
We have previously described a developmentally regulated mRNA in maize that accumulates in mature embryos and is involved in a variety of stress responses in the plant. The sequence of the encoded 16 kDa protein (MA16) predicts that it is an RNA-binding protein, since it possesses a ribonucleoprotein consensus sequence-type RNA-binding domain (CS-RBD). To assess the predicted RNA binding property of the protein and as a starting point to characterize its function we have used ribohomopolymer-binding assays. Here we show that the MA16-encoded protein binds preferentially to uridine- and guanosine-rich RNAs. In light of these results a likely role for this protein in RNA metabolism during late embryogenesis and in the stress response is discussed. 相似文献
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Hu H Kolesnikov A Riggs JR Wesson KE Stephens R Leahy EM Shrader WD Sprengeler PA Green MJ Sanford E Nguyen M Gjerstad E Cabuslay R Young WB 《Bioorganic & medicinal chemistry letters》2006,16(17):4567-4570
The 4-amino-5-azaindole as an amidino-benzimidazole replacement is described. A series of potent and selective analogs were discovered and showed desirable ex vivo efficacy as measured by PT. 相似文献
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Young WB Sprengeler P Shrader WD Li Y Rai R Verner E Jenkins T Fatheree P Kolesnikov A Janc JW Cregar L Elrod K Katz B 《Bioorganic & medicinal chemistry letters》2006,16(3):710-713
Inhibition of coagulation proteases such as thrombin, fXa, and fVIIa has been a focus of ongoing research to produce safe and effective antithrombotic agents. Herein, we describe a unique zinc-mediated chelation strategy to streamline the discovery of potent inhibitors of fIIa, fXa, and fVIIa. SAR studies that led to the development of selective inhibitors of fXa will also be detailed. 相似文献
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Vijaykumar D Rai R Shaghafi M Ton T Torkelson S Leahy EM Riggs JR Hu H Sprengeler PA Shrader WD O'Bryan C Cabuslay R Sanford E Gjerstadt E Liu L Sukbuntherng J Young WB 《Bioorganic & medicinal chemistry letters》2006,16(14):3829-3832
Efforts toward developing orally bioavailable factor VIIa inhibitors starting from parenteral lead compound 1 are described. SAR resulted in improved physicochemical properties, leading to enhanced oral absorption in rat. 相似文献
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Young WB Rai R Shrader WD Burgess-Henry J Hu H Elrod KC Sprengeler PA Katz BA Sukbuntherng J Mordenti J 《Bioorganic & medicinal chemistry letters》2006,16(7):2034-2036
Plasma kallikrein is a serine protease that is involved in pathways of inflammation, complement fixation, coagulation, and fibrinolysis. Herein, we describe the SAR and structural binding modes of a series of inhibitors of plasma kallikrein as well as the pharmacokinetics of a lead analog 11 in rat. 相似文献
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Shrader WD Kolesnikov A Burgess-Henry J Rai R Hendrix J Hu H Torkelson S Ton T Young WB Katz BA Yu C Tang J Cabuslay R Sanford E Janc JW Sprengeler PA 《Bioorganic & medicinal chemistry letters》2006,16(6):1596-1600
Within the trypsin family of coagulation proteases, obtaining highly selective inhibitors of factor VIIa has been challenging. We report a series of factor VIIa (fVIIa) inhibitors based on the 5-amidino-2-(2-hydroxy-biphenyl-3-yl)-benzimidazole (1) scaffold with potency for fVIIa and high selectivity against factors IIa, Xa, and trypsin. With this scaffold class, we propose that a unique hydrogen bond interaction between a hydroxyl on the distal ring of the biaryl system and the backbone carbonyl of fVIIa lysine-192 provides a basis for enhanced selectivity and potency for fVIIa. 相似文献
18.
Microorganisms are associated with a variety of ancient geological materials. However, conclusive proof that these organisms
are as old as the geological material and not more recent introductions has generally been lacking. Over the years, numerous
reports of the isolation of ancient bacteria from geological materials have appeared. Most of these have suffered from the
fact that the protocol for the surface sterilization of the sample was either poorly defined, inadequate or rarely included
data to validate the overall effectiveness of the sterilization protocol. With proper sterility validation and isolation protocol,
a legitimate claim for the isolation of an ancient microbe can be made. Biochemical, physiological, or morphological data
indicate that these ancient microbes are not significantly different from modern isolates. As the role (decomposition) of
modern and ancient microbes has not changed over time, it is probably unreasonable to expect these organisms to be vastly
different. A discussion on the reasons for the homogeneity of ancient and modern microbes is presented. Journal of Industrial Microbiology & Biotechnology (2002) 28, 32–41 DOI: 10.1038/sj/jim/7000174
Received 20 May 2001/ Accepted in revised form 16 June 2001 相似文献
19.
The N-end rule in Escherichia coli: cloning and analysis of the leucyl, phenylalanyl-tRNA-protein transferase gene aat. 总被引:2,自引:0,他引:2 下载免费PDF全文
The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. Distinct versions of the N-end rule operate in bacteria, fungi, and mammals. We report the cloning and analysis of aat, the Escherichia coli gene that encodes leucyl, phenylalanyl-tRNA-protein transferase (L/F-transferase), a component of the bacterial N-end rule pathway. L/F-transferase is required for the degradation of N-end rule substrates bearing an N-terminal arginine or lysine. The aat gene maps to the 19-min region of the E. coli chromosome and encodes a 234-residue protein whose sequence lacks significant similarities to sequences in data bases. In vitro, L/F-transferase catalyzes the posttranslational conjugation of leucine or phenylalanine to the N termini of proteins that bear an N-terminal arginine or lysine. However, the isolation and sequence analysis of a beta-galactosidase variant engineered to expose an N-terminal arginine in vivo revealed the conjugation of leucine but not of phenylalanine to the N terminus of the beta-galactosidase variant. Thus, the specificity of L/F-transferase in vivo may be greater than that in vitro. The aat gene is located approximately 1 kb from clpA, which encodes a subunit of ATP-dependent protease Clp. Although both aat and clpA are required for the degradation of certain N-end rule substrates, their nearly adjacent genes are convergently transcribed. The aat gene lies downstream of an open reading frame that encodes a homolog of the mammalian multidrug resistance P glycoproteins. 相似文献
20.
Tang J Yu CL Williams SR Springman E Jeffery D Sprengeler PA Estevez A Sampang J Shrader W Spencer J Young W McGrath M Katz BA 《The Journal of biological chemistry》2005,280(49):41077-41089
Plasma kallikrein is a serine protease that has many important functions, including modulation of blood pressure, complement activation, and mediation and maintenance of inflammatory responses. Although plasma kallikrein has been purified for 40 years, its structure has not been elucidated. In this report, we described two systems (Pichia pastoris and baculovirus/Sf9 cells) for expression of the protease domain of plasma kallikrein, along with the purification and high resolution crystal structures of the two recombinant forms. In the Pichia pastoris system, the protease domain was expressed as a heterogeneously glycosylated zymogen that was activated by limited trypsin digestion and treated with endoglycosidase H deglycosidase to reduce heterogeneity from the glycosylation. The resulting protein was chromatographically resolved into four components, one of which was crystallized. In the baculovirus/Sf9 system, homogeneous, crystallizable, and nonglycosylated protein was expressed after mutagenizing three asparagines (the glycosylation sites) to glutamates. When assayed against the peptide substrates, pefachrome-PK and oxidized insulin B chain, both forms of the protease domain were found to have catalytic activity similar to that of the full-length protein. Crystallization and x-ray crystal structure determination of both forms have yielded the first three-dimensional views of the catalytic domain of plasma kallikrein. The structures, determined at 1.85 A for the endoglycosidase H-deglycosylated protease domain produced from P. pastoris and at 1.40 A for the mutagenically deglycosylated form produced from Sf9 cells, show that the protease domain adopts a typical chymotrypsin-like serine protease conformation. The structural information provides insights into the biochemical and enzymatic properties of plasma kallikrein and paves the way for structure-based design of protease inhibitors that are selective either for or against plasma kallikrein. 相似文献