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991.
992.
Over-expression of STP13, a hexose transporter, improves plant growth and nitrogen use in Arabidopsis thaliana seedlings 总被引:1,自引:0,他引:1
In Arabidopsis thaliana , the regulation of hexose levels by the large monosaccharide transporter (MST) gene family influences many aspects of plant growth. The cloning and transgenic expression of one family member (STP13) enabled the manipulation of carbon (C) and nitrogen (N) metabolism in Arabidopsis . Transgenic seedlings constitutively over-expressing STP13 (STP13OX) had increased rates of glucose uptake, higher endogenous sucrose levels and accumulated more total C and biomass per plant when grown on soil-less media supplemented with 55 m m glucose and sufficient N (9 m m nitrate). Furthermore, STP13OX seedlings acquired 90% more total N than the Col-0 seedlings, and had higher levels of expression of the nitrate transporter NRT2.2 . In addition, STP13OX seedlings were larger and had higher biomass than Col-0 seedlings when grown under a limiting N condition (3 m m nitrate). Transgene analysis of STP13 reveals that its gene product is localized to the plasma membrane (PM) in tobacco BY-2 suspension cells, that it encodes a functional MST in planta , and that the STP13 promoter directs GUS expression to the vasculature and to leaf mesophyll cells. This work highlights the link between C and N metabolism, demonstrating that a plant's N use may be improved by increasing the availability of C. 相似文献
993.
Determination of the target nucleosides for members of two families of 16S rRNA methyltransferases that confer resistance to partially overlapping groups of aminoglycoside antibiotics
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Miloje Savic Josip Lovri? Tatjana Ilic Tomic Branka Vasiljevic Graeme L. Conn 《Nucleic acids research》2009,37(16):5420-5431
The 16S ribosomal RNA methyltransferase enzymes that modify nucleosides in the drug binding site to provide self-resistance in aminoglycoside-producing micro-organisms have been proposed to comprise two distinct groups of S-adenosyl-l-methionine (SAM)-dependent RNA enzymes, namely the Kgm and Kam families. Here, the nucleoside methylation sites for three Kgm family methyltransferases, Sgm from Micromonospora zionensis, GrmA from Micromonospora echinospora and Krm from Frankia sp. Ccl3, were experimentally determined as G1405 by MALDI-ToF mass spectrometry. These results significantly extend the list of securely characterized G1405 modifying enzymes and experimentally validate their grouping into a single enzyme family. Heterologous expression of the KamB methyltransferase from Streptoalloteichus tenebrarius experimentally confirmed the requirement for an additional 60 amino acids on the deduced KamB N-terminus to produce an active methyltransferase acting at A1408, as previously suggested by an in silico analysis. Finally, the modifications at G1405 and A1408, were shown to confer partially overlapping but distinct resistance profiles in Escherichia coli. Collectively, these data provide a more secure and systematic basis for classification of new aminoglycoside resistance methyltransferases from producers and pathogenic bacteria on the basis of their sequences and resistance profiles. 相似文献
994.
Andrew S. Felts Sam A. Saleh Uyen Le Alice L. Rodriguez C. David Weaver P. Jeffrey Conn Craig W. Lindsley Kyle A. Emmitte 《Bioorganic & medicinal chemistry letters》2009,19(23):6623-6626
A high-throughput cell-based screen identified a series of 6-substituted-4-anilinoquinazolines as non-competitive antagonists of metabotropic glutamate receptor 5 (mGlu5). This Letter describes the SAR of this series and the profile of selected compounds in selectivity and radioligand binding assays. 相似文献
995.
Richard Williams Kari A. Johnson Patrick R. Gentry Colleen M. Niswender Charles D. Weaver P. Jeffrey Conn Craig W. Lindsley Corey R. Hopkins 《Bioorganic & medicinal chemistry letters》2009,19(17):4967-4970
This Letter describes the synthesis and SAR of the novel positive allosteric modulator, VU0155041, a compound that has shown in vivo efficacy in rodent models of Parkinson’s disease. The synthesis takes advantage of an iterative parallel synthesis approach to rapidly synthesize and evaluate a number of analogs of VU0155041. 相似文献
996.
Munns R James RA Xu B Athman A Conn SJ Jordans C Byrt CS Hare RA Tyerman SD Tester M Plett D Gilliham M 《Nature biotechnology》2012,30(4):360-364
The ability of wheat to maintain a low sodium concentration ([Na(+)]) in leaves correlates with improved growth under saline conditions. This trait, termed Na(+) exclusion, contributes to the greater salt tolerance of bread wheat relative to durum wheat. To improve the salt tolerance of durum wheat, we explored natural diversity in shoot Na(+) exclusion within ancestral wheat germplasm. Previously, we showed that crossing of Nax2, a gene locus in the wheat relative Triticum monococcum into a commercial durum wheat (Triticum turgidum ssp. durum var. Tamaroi) reduced its leaf [Na(+)] (ref. 5). Here we show that a gene in the Nax2 locus, TmHKT1;5-A, encodes a Na(+)-selective transporter located on the plasma membrane of root cells surrounding xylem vessels, which is therefore ideally localized to withdraw Na(+) from the xylem and reduce transport of Na(+) to leaves. Field trials on saline soils demonstrate that the presence of TmHKT1;5-A significantly reduces leaf [Na(+)] and increases durum wheat grain yield by 25% compared to near-isogenic lines without the Nax2 locus. 相似文献
997.
998.
Melancon BJ Lamers AP Bridges TM Sulikowski GA Utley TJ Sheffler DJ Noetzel MJ Morrison RD Scott Daniels J Niswender CM Jones CK Conn PJ Lindsley CW Wood MR 《Bioorganic & medicinal chemistry letters》2012,22(2):1044-1048
This Letter describes the continued optimization of an MLPCN probe molecule (ML012) through an iterative parallel synthesis approach. After exploring extensive modifications throughout the parent structure, we arrived at a more highly M(1)-selective antagonist, compound 13l (VU0415248). Muscarinic subtype selectivity across all five human and rat receptors for 13l, along with rat selectivity for the lead compound (ML012), is presented. 相似文献
999.
Salovich JM Vinson PN Sheffler DJ Lamsal A Utley TJ Blobaum AL Bridges TM Le U Jones CK Wood MR Daniels JS Conn PJ Niswender CM Lindsley CW Hopkins CR 《Bioorganic & medicinal chemistry letters》2012,22(15):5084-5088
Herein we describe the discovery and development of a novel class of M(4) positive allosteric modulators, culminating in the discovery of ML293. ML293 exhibited modest potency at the human M4 receptor (EC(50)=1.3 μM) and excellent efficacy as noted by the 14.6-fold leftward shift of the agonist concentration-response curve. ML293 was also selective versus the other muscarinic subtypes and displayed excellent in vivo PK properties in rat with low IV clearance (11.6 mL/min/kg) and excellent brain exposure (PO PBL, 10 mg/kg at 1h, [Brain]=10.3 μM, B:P=0.85). 相似文献
1000.
Sheffler DJ Wenthur CJ Bruner JA Carrington SJ Vinson PN Gogi KK Blobaum AL Morrison RD Vamos M Cosford ND Stauffer SR Daniels JS Niswender CM Conn PJ Lindsley CW 《Bioorganic & medicinal chemistry letters》2012,22(12):3921-3925
Herein we report the discovery and SAR of a novel metabotropic glutamate receptor 3 (mGlu(3)) NAM probe (ML289) with 15-fold selectivity versus mGlu(2). The mGlu(3) NAM was discovered via a 'molecular switch' from a closely related, potent mGlu(5) positive allosteric modulator (PAM), VU0092273. This NAM (VU0463597, ML289) displays an IC(50) value of 0.66 μM and is inactive against mGlu(5). 相似文献