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991.
Tiralongo J Ashikov A Routier F Eckhardt M Bakker H Gerardy-Schahn R von Itzstein M 《Glycobiology》2006,16(1):73-81
The architectural conservation of nucleotide sugar transport proteins (NSTs) enabled the theoretical prediction of putative NSTs in diverse gene databases. In the human genome, 17 NST sequences have been identified but only six have been unequivocally characterized with respect to their transport specificities. Defining transport characteristics of recombinant NSTs has become a major challenge because true zero background systems are widely absent. Production of recombinant NSTs in heterologous systems has developed multifunctionality for some NSTs leading to a novel level of complexity in the field. Assuming that (1) the specificity of NSTs is determined at the primary sequence level and (2) the proteins are autonomously functional units, final definition of the substrate specificity will depend on the use of isolated transport proteins. Herein, we describe the first report of the functional expression of mouse CMP-sialic acid transporter (CST) in Escherichia coli and thus provide significant progress towards the production of transporter proteins in quantities suitable for functional and structural analyses. Recovery of the active NST from inclusion bodies was achieved after solubilization with 8 M urea and stepwise renaturation. After reconstitution into phospholipid vesicles, the recombinant protein demonstrated specific transport for CMP-N-acetylneuraminic acid (CMP-Neu5Ac) with no transport of UDP-sugars. Kinetic studies carried out with CMP-Neu5Ac and established CMP-Neu5Ac antagonist's evaluated natural conformation of the reconstituted protein and clearly demonstrate that the transporter acts as a simple mobile carrier. 相似文献
992.
993.
Miguel Angel Jimnez-Montao 《Bio Systems》2009,98(2):105-114
We describe a compact representation of the genetic code that factorizes the table in quartets. It represents a “least grammar” for the genetic language. It is justified by the Klein-4 group structure of RNA bases and codon doublets. The matrix of the outer product between the column-vector of bases and the corresponding row-vector VT = (C G U A), considered as signal vectors, has a block structure consisting of the four cosets of the K × K group of base transformations acting on doublet AA. This matrix, translated into weak/strong (W/S) and purine/pyrimidine (R/Y) nucleotide classes, leads to a code table with mixed and unmixed families in separate regions. A basic difference between them is the non-commuting (R/Y) doublets: AC/CA, GU/UG. We describe the degeneracy in the canonical code and the systematic changes in deviant codes in terms of the divisors of 24, employing modulo multiplication groups. We illustrate binary sub-codes characterizing mutations in the quartets. We introduce a decision-tree to predict the mode of tRNA recognition corresponding to each codon, and compare our result with related findings by Jestin and Soulé [Jestin, J.-L., Soulé, C., 2007. Symmetries by base substitutions in the genetic code predict 2′ or 3′ aminoacylation of tRNAs. J. Theor. Biol. 247, 391–394], and the rearrangements of the table by Delarue [Delarue, M., 2007. An asymmetric underlying rule in the assignment of codons: possible clue to a quick early evolution of the genetic code via successive binary choices. RNA 13, 161–169] and Rodin and Rodin [Rodin, S.N., Rodin, A.S., 2008. On the origin of the genetic code: signatures of its primordial complementarity in tRNAs and aminoacyl-tRNA synthetases. Heredity 100, 341–355], respectively. 相似文献
994.
995.
Mary T. Didiuk David A. Griffith John W. Benbow Kevin K.C. Liu Daniel P. Walker F. Christopher Bi Joel Morris Angel Guzman-Perez Hua Gao Bruce M. Bechle Ryan M. Kelley Xiaojing Yang Kenneth Dirico Syed Ahmed William Hungerford Joseph DiBrinno Michael P. Zawistoski Scott W. Bagley Jianke Li Yuan Zeng Kosea S. Frederick 《Bioorganic & medicinal chemistry letters》2009,19(16):4555-4559
Synthesis and structure–activity relationship (SAR) studies on 5-trifluoromethylpyrido[4,3-d]pyrimidin-4(3H)-ones, a novel class of calcium receptor antagonists is described with particular emphasis on optimization of the pharmacokinetic/pharmacodynamic parameters required for a short duration of action compound. Orally-active compounds were identified which displayed the desired animal pharmacology (rapid and transient stimulation of parathyroid hormone) essential for bone anabolic effects. 相似文献
996.
997.
Angel A. Recio Despaigne Jeferson G. Da Silva Ana Cerúlia M. do Carmo Oscar E. Piro Eduardo E. Castellano Heloisa Beraldo 《Inorganica chimica acta》2009,362(7):2117-2122
2-Benzoylpyridine-phenylhydrazone (H2BzPh), 2-benzoylpyridine-para-chloro-phenylhydrazone (H2BzpClPh), and 2-benzoylpyridine-para-nitro-phenyl (H2BzpNO2Ph) hydrazone were obtained and fully characterized, as well as their zinc(II) complexes [Zn(H2BzPh)Cl2] (1), [Zn(H2BzClPh)Cl2] (2) and [Zn(H2BzpNO2Ph)Cl2] (3). During the syntheses of complex 1 a second product crystallized, which was characterized as [Zn(2BzPh)2] (1a). Upon re-crystallization in 1:9 DMSO:acetone conversion of 2 into [Zn(H2BzpClPh)Cl2] · H2O (2a) and of 3 into [Zn(2BzpNO2Ph)Cl(DMSO)] (3a) occurred. The crystal structures of 1a, 2a and 3a were determined. In 1a the two nearly perpendicular H2BzPh ligands give rise to a distorted octahedral environment around the metal. The 5-fold coordination around the metal is completed with two chloride ions in 2a and with one chloride and one oxygen atom from DMSO in 3a. 相似文献
998.
The effects of non-heme iron binding on the function, structure, and stability of a monomeric phenylalanine hydroxylase from
the thermophile Chloroflexus aurantiacus (caPAH) were investigated. Comparative studies on holo (iron-bound) and apo (iron-depleted) caPAH indicated that iron(II)
binding does not significantly affect the overall structure of the enzyme. Thermal denaturation studies performed using differential
scanning calorimetry showed that the unfolding reaction was kinetically controlled and that holo-caPAH displayed a large increase
in thermal stability (approximately 15 °C upshift in the T
m value) compared with the apoenzyme. Analysis using a simple irreversible two-state model also showed a higher kinetic stability
for holo-caPAH at optimal growth temperature (denaturing approximately 8 times more slowly than the apo form at 55 °C). Experiments
performed in the presence of urea in combination with structure–energetics calculations suggest that iron binding reduces
the change in accessible surface area exposed in the unfolding transition state (from approximately 36% to approximately 5%
of the total change in accessible surface area) and also the surface involved in water-unsatisfied broken internal contacts
(solvation barriers). Additional comparative analyses using phenylalanine hydroxylase from mesophilic and psychrophilic organisms
suggest that, in addition to its catalytic role, the non-heme iron serves to enhance the kinetic stability of phenylalanine
hydroxylase at the optimal growth temperature of the organism.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
999.
Ronghui Lin Sigmond G. Johnson Peter J. Connolly Steven K. Wetter Eva Binnun Terry V. Hughes William V. Murray Niranjan B. Pandey Sandra J. Moreno-Mazza Mary Adams Angel R. Fuentes-Pesquera Steven A. Middleton 《Bioorganic & medicinal chemistry letters》2009,19(8):2333-2337
2,7-Diamino-thiazolo[4,5-d]pyrimidine analogues were synthesized as novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Representative compounds showed potent and selective EGFR inhibitory activities and inhibited in vitro cellular proliferation in EGFR-overexpressing human tumor cells. The synthesis and preliminary biological, physical, and pharmacokinetic evaluation of these thiazolopyrimidine compounds are reported. 相似文献
1000.
Andreas Weiss Miriam Bibel Vanita Chopra Jonathan Fox Kimberly Kegel Stephan Grueninger David Housman H. Diana Rosas Scott Zeitlin Paolo Paganetti 《Analytical biochemistry》2009,395(1):8-1414
The genetic mutation causing Huntington’s disease is a polyglutamine expansion in the huntingtin protein where more than 37 glutamines cause disease by formation of toxic intracellular fragments, aggregates, and cell death. Despite a clear pathogenic role for mutant huntingtin, understanding huntingtin expression during the presymptomatic phase of the disease or during disease progression has remained obscure. Central to clarifying the role in the pathomechanism of disease is the ability to easily and accurately measure mutant huntingtin in accessible human tissue samples as well as cell and animal models. Here we describe a highly sensitive time-resolved Förster resonance energy transfer (FRET) assay for quantification of soluble mutant huntingtin in brain, plasma, and cerebrospinal fluid. Surprisingly, in mice, soluble huntingtin levels decrease during disease progression, inversely correlating with brain aggregate load. Mutant huntingtin is easily detected in human brain and blood-derived fractions, providing a utility to assess mutant huntingtin expression during disease course as well as a pharmacodynamic marker for disease-modifying therapeutics targeting expression, cleavage, or degradation of mutant huntingtin. The design of the homogeneous one-step method for huntingtin detection is such that it can be easily applied to measure other proteins of interest. 相似文献