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Query: EC:6.2.1.1 (ACS)
 78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many cellular processes are regulated by the reversible phosphorylation of proteins. Despite the importance of monitoring protein phosphorylation, available methods to modify and enrich phosphopeptides from complex mixtures for subsequent mass spectrometric analysis are challenging. Here the oxidation-reduction condensation was shown for the first time to directly modify the phosphate of phosphopeptides and phosphoproteins. By coupling with a solid-phase resin, the oxidation-reduction condensation was validated for capture and recovery of phosphoserine-, phosphothreonine-, and phosphotyrosine-containing peptides from a peptide mixture. In addition, full-length phosphoproteins or phosphopeptides from a protein digestion were captured and recovered using the oxidation-reduction condensation, demonstrating its compatibility with protein mixtures. The strategy modifies all phosphopeptides, maintains high chemical selectivity, requires only two steps, and relies on commercially available reagents, suggesting that the oxidation-reduction condensation has the potential to enhance phosphopeptide enrichment methods and encourage development of efficient biochemical and proteomics tools targeting phosphorylation.
ACS Chem Biol 2006 Dec 20
PMID:Phosphopeptide modification and enrichment by oxidation-reduction condensation. 1718 34

The genome sequence of Roseovarius sp. strain 217 indicated that many pathway enzymes found in other organisms for the degradation of taurine are represented, but that a novel, apparently energy-dependent pathway is involved in the conversion of acetyl phosphate to acetyl CoA. Thus, an ABC transporter for taurine could be postulated, while inducible taurine: pyruvate aminotransferase, alanine dehydrogenase, sulfoacetaldehyde acetyltransferase and sulfite dehydrogenase could be assayed. Whereas phosphate acetyltransferase has been found in other organisms, none was indicated in the genome sequence and no activity was found in cell-free extracts. Instead, acetate kinase was active as was acetate-CoA ligase.
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PMID:Roseovarius sp. strain 217: aerobic taurine dissimilation via acetate kinase and acetate-CoA ligase. 1742 60

Protein kinase B (PKB/Akt) plays a key role in cell signaling. The PH domain of PKB binds phosphatidylinositol 3,4,5-trisphosphate translocating PKB to the plasma membrane for activation by 3-phosphoinositide-dependent protein kinase 1. The crystal structure of the headgroup inositol 1,3,4,5-tetrakisphosphate Ins(1,3,4,5)P4-PKB complex facilitates in silico ligand design. The novel achiral analogue benzene 1,2,3,4-tetrakisphosphate (Bz(1,2,3,4)P4) possesses phosphate regiochemistry different from that of Ins(1,3,4,5)P4 and surprisingly binds with similar affinity as the natural headgroup. Bz(1,2,3,4)P4 co-crystallizes with the PKBalpha PH domain in a fashion also predictable in silico. The 2-phosphate of Bz(1,2,3,4)P4 does not interact with any residue, and the D5-phosphate of Ins(1,3,4,5)P4 is not mimicked by Bz(1,2,3,4)P4. Bz(1,2,3,4)P4 is an example of a simple inositol phosphate surrogate crystallized in a protein, and this approach could be applied to design modulators of inositol polyphosphate binding proteins.
ACS Chem Biol 2007 Apr 24
PMID:Novel inositol phospholipid headgroup surrogate crystallized in the pleckstrin homology domain of protein kinase Balpha. 1743 22

A convenient new method is described for the introduction of ketone groups at the N-termini of antibodies. The reaction occurs in the presence of pyridoxal-5'-phosphate under conditions mild enough to maintain antigen binding function, as confirmed by enzyme-linked immunosorbent assay. Further derivatization of these functional sites was accomplished through oxime formation, yielding well-defined antibody conjugates for a wide range of applications. The ability of the modified antibodies to bind their targets was confirmed via immunodot blot analysis. The generality of this method has been demonstrated on a number of monoclonal and polyclonal antibodies, all with different binding specificities.
ACS Chem Biol 2007 Apr 24
PMID:Regioselective labeling of antibodies through N-terminal transamination. 1745 1

Protein kinases catalyze the transfer of the gamma-phosphate of ATP to a protein substrate and thereby profoundly alter the properties of the phosphorylated protein. The identification of the substrates of protein kinases has proven to be a very difficult task because of the multitude of structurally related protein kinases present in cells, their apparent redundancy of function, and the lack of absolute specificity of small-molecule inhibitors. Here, we review approaches that utilize chemical genetics to determine the functions and substrates of protein kinases, focusing on the design of ATP analogues and protein kinase binding site mutants.
ACS Chem Biol 2007 May 22
PMID:Using chemical genetics and ATP analogues to dissect protein kinase function. 1751 31

The response of the central carbon metabolism of Escherichia coli to temperature-induced recombinant production of human fibroblast growth factor was studied on the level of metabolic fluxes and intracellular metabolite levels. During production, E. coli TG1:plambdaFGFB, carrying a plasmid encoded gene for the recombinant product, revealed stress related characteristics such as decreased growth rate and biomass yield and enhanced by-product excretion (acetate, pyruvate, lactate). With the onset of production, the adenylate energy charge dropped from 0.85 to 0.60, indicating the occurrence of a severe energy limitation. This triggered an increase of the glycolytic flux which, however, was not sufficient to compensate for the increased ATP demand. The activation of the glycolytic flux was also indicated by the readjustment of glycolytic pool sizes leading to an increased driving force for the reaction catalyzed by phosphofructokinase. Moreover, fluxes through the TCA cycle, into the pentose phosphate pathway and into anabolic pathways decreased significantly. The strong increase of flux into overflow pathways, especially towards acetate was most likely caused by a flux redirection from pyruvate dehydrogenase to pyruvate oxidase. The glyoxylate shunt, not active during growth, was the dominating anaplerotic pathway during production. Together with pyruvate oxidase and acetyl CoA synthase this pathway could function as a metabolic by-pass to overcome the limitation in the junction between glycolysis and TCA cycle and partly recycle the acetate formed back into the metabolism.
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PMID:Response of fluxome and metabolome to temperature-induced recombinant protein synthesis in Escherichia coli. 1768 98

The ion exchange membrane bioreactor (IEMB) proved to be an effective technology for the removal of nitrate and perchlorate from polluted drinking water when using a mono-anion permselective membrane such as Neosepta ACS. Aiming at reducing the cost of the system, this study evaluates the use of a lower-cost anion exchange membrane, which exhibits no preferential mono-anion permselective properties. With this purpose an Excellion I-200 membrane was tested, for the removal of anionic micropollutants, such as nitrate and perchlorate from drinking water supplies. The impact of the lower anion permselectivity of this membrane on the quality of the treated water was determined. It was demonstrated that differences between the membrane properties are responsible for the different permselectivities observed towards multi-valent and mono-valent anions. The use of Excellion I-200 resulted in a less selective removal of perchlorate and nitrate, allowing anions such as sulphate and phosphate species to be transported. When treating 3.1l/m(2)h of water contaminated with 100microg/l of perchlorate and 60mg/l of nitrate, lower removal degrees were obtained (85% of perchlorate and 88% of nitrate), compared with 96% of perchlorate and 99% of nitrate achieved with the Neosepta ACS membrane, operating under the same conditions. However, the Excellion I-200 membrane shows no target anion flux decline during a relatively long period of operation (1 month) and no secondary contamination of the treated water by the carbon source used. These characteristics are essential for a membrane to be successfully used in the IEMB system. Additionally, the selection of the membrane depends on the latter characteristics and on the water quality requirements.
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PMID:Removal of mono-valent oxyanions from water in an ion exchange membrane bioreactor: influence of membrane permselectivity. 1805 85

In Archaea, acetate formation and ATP synthesis from acetyl-CoA is catalyzed by an unusual ADP-forming acetyl-CoA synthetase (ACD) (acetyl-CoA + ADP + P(i) acetate + ATP + HS-CoA) catalyzing the formation of acetate from acetyl-CoA and concomitant ATP synthesis by the mechanism of substrate level phosphorylation. ACD belongs to the protein superfamily of nucleoside diphosphate-forming acyl-CoA synthetases, which also include succinyl-CoA synthetases (SCSs). ACD differs from SCS in domain organization of subunits and in the presence of a second highly conserved histidine residue in the beta-subunit, which is absent in SCS. The influence of these differences on structure and reaction mechanism of ACD was studied with heterotetrameric ACD (alpha(2)beta(2)) from the hyperthermophilic archaeon Pyrococcus furiosus in comparison with heterotetrameric SCS. A structural model of P. furiosus ACD was constructed suggesting a novel spatial arrangement of the subunits different from SCS, however, maintaining a similar catalytic site. Furthermore, kinetic and molecular properties and enzyme phosphorylation as well as the ability to catalyze arsenolysis of acetyl-CoA were studied in wild type ACD and several mutant enzymes. The data indicate that the formation of enzyme-bound acetyl phosphate and enzyme phosphorylation at His-257alpha, respectively, proceed in analogy to SCS. In contrast to SCS, in ACD the phosphoryl group is transferred from the His-257alpha to ADP via transient phosphorylation of a second conserved histidine residue in the beta-subunit, His-71beta. It is proposed that ACD reaction follows a novel four-step mechanism including transient phosphorylation of two active site histidine residues:
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PMID:Reaction mechanism and structural model of ADP-forming Acetyl-CoA synthetase from the hyperthermophilic archaeon Pyrococcus furiosus: evidence for a second active site histidine residue. 1837 46

We have studied the sphingosine 1-phosphate (S1P) receptor system to better understand why certain molecular targets within a closely related family are much more tractable when identifying compelling chemical leads. Five medically important G-protein-coupled receptors for S1P regulate heart rate, coronary artery caliber, endothelial barrier integrity, and lymphocyte trafficking. Selective S1P receptor agonist probes would be of great utility to study receptor subtype-specific function. Through systematic screening of the same libraries, we identified novel selective agonist chemotypes for each of the S1P1 and S1P3 receptors. Ultrahigh-throughput screening (uHTS) for S1P1 was more effective than that for S1P3, with many selective, low nanomolar hits of proven mechanism emerging. Receptor structure modeling and ligand docking reveal differences between the receptor binding pockets, which are the basis for subtype selectivity. Novel selective agonists interact primarily in the hydrophobic pocket of the receptor in the absence of headgroup interactions. Chemistry-space and shape-based analysis of the screening libraries in combination with the binding models explain the observed differential hit rates and enhanced efficiency for lead discovery for S1P1 versus S1P3 in this closely related receptor family.
ACS Chem Biol 2008 Aug 15
PMID:Ligand-binding pocket shape differences between sphingosine 1-phosphate (S1P) receptors S1P1 and S1P3 determine efficiency of chemical probe identification by ultrahigh-throughput screening. 1859 Mar 33

A new synthetic method allows incorporation of 13C or 15N into selected positions within purine nucleotide bases, starting from simple labeled precursors. The procedure harnesses diverse enzymes to support biosynthesis by the pentose phosphate and de novo purine pathways. Selective isotope incorporation should expand the range of RNAs that are amenable to NMR analysis.
ACS Chem Biol 2008 Aug 15
PMID:The purine machine scores a base hit. 1870 57


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