Wagner A

References (8)

Title : Characterization and engineering of a plastic-degrading aromatic polyesterase - Austin_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4350
Author(s) : Austin HP , Allen MD , Donohoe BS , Rorrer NA , Kearns FL , Silveira RL , Pollard BC , Dominick G , Duman R , El Omari K , Mykhaylyk V , Wagner A , Michener WE , Amore A , Skaf MS , Crowley MF , Thorne AW , Johnson CW , Woodcock HL , McGeehan JE , Beckham GT
Ref : Proc Natl Acad Sci U S A , 115 :E4350 , 2018
Abstract : Poly(ethylene terephthalate) (PET) is one of the most abundantly produced synthetic polymers and is accumulating in the environment at a staggering rate as discarded packaging and textiles. The properties that make PET so useful also endow it with an alarming resistance to biodegradation, likely lasting centuries in the environment. Our collective reliance on PET and other plastics means that this buildup will continue unless solutions are found. Recently, a newly discovered bacterium, Ideonella sakaiensis 201-F6, was shown to exhibit the rare ability to grow on PET as a major carbon and energy source. Central to its PET biodegradation capability is a secreted PETase (PET-digesting enzyme). Here, we present a 0.92 A resolution X-ray crystal structure of PETase, which reveals features common to both cutinases and lipases. PETase retains the ancestral alpha/beta-hydrolase fold but exhibits a more open active-site cleft than homologous cutinases. By narrowing the binding cleft via mutation of two active-site residues to conserved amino acids in cutinases, we surprisingly observe improved PET degradation, suggesting that PETase is not fully optimized for crystalline PET degradation, despite presumably evolving in a PET-rich environment. Additionally, we show that PETase degrades another semiaromatic polyester, polyethylene-2,5-furandicarboxylate (PEF), which is an emerging, bioderived PET replacement with improved barrier properties. In contrast, PETase does not degrade aliphatic polyesters, suggesting that it is generally an aromatic polyesterase. These findings suggest that additional protein engineering to increase PETase performance is realistic and highlight the need for further developments of structure/activity relationships for biodegradation of synthetic polyesters.
ESTHER : Austin_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4350
PubMedSearch : Austin_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4350
PubMedID: 29666242
Gene_locus related to this paper: idesa-peth

Title : Molecular characterisation of transport mechanisms at the developing mouse blood-CSF interface: a transcriptome approach - Liddelow_2012_PLoS.One_7_e33554
Author(s) : Liddelow SA , Temple S , Mollgard K , Gehwolf R , Wagner A , Bauer H , Bauer HC , Phoenix TN , Dziegielewska KM , Saunders NR
Ref : PLoS ONE , 7 :e33554 , 2012
Abstract : Exchange mechanisms across the blood-cerebrospinal fluid (CSF) barrier in the choroid plexuses within the cerebral ventricles control access of molecules to the central nervous system, especially in early development when the brain is poorly vascularised. However, little is known about their molecular or developmental characteristics. We examined the transcriptome of lateral ventricular choroid plexus in embryonic day 15 (E15) and adult mice. Numerous genes identified in the adult were expressed at similar levels at E15, indicating substantial plexus maturity early in development. Some genes coding for key functions (intercellular/tight junctions, influx/efflux transporters) changed expression during development and their expression patterns are discussed in the context of available physiological/permeability results in the developing brain. Three genes: Secreted protein acidic and rich in cysteine (Sparc), Glycophorin A (Gypa) and C (Gypc), were identified as those whose gene products are candidates to target plasma proteins to choroid plexus cells. These were investigated using quantitative- and single-cell-PCR on plexus epithelial cells that were albumin- or total plasma protein-immunopositive. Results showed a significant degree of concordance between plasma protein/albumin immunoreactivity and expression of the putative transporters. Immunohistochemistry identified SPARC and GYPA in choroid plexus epithelial cells in the embryo with a subcellular distribution that was consistent with transport of albumin from blood to cerebrospinal fluid. In adult plexus this pattern of immunostaining was absent. We propose a model of the cellular mechanism in which SPARC and GYPA, together with identified vesicle-associated membrane proteins (VAMPs) may act as receptors/transporters in developmentally regulated transfer of plasma proteins at the blood-CSF interface.
ESTHER : Liddelow_2012_PLoS.One_7_e33554
PubMedSearch : Liddelow_2012_PLoS.One_7_e33554
PubMedID: 22457777

Title : First efficient uncharged reactivators for the dephosphylation of poisoned human acetylcholinesterase - Mercey_2011_Chem.Commun.(Camb)_47_5295
Author(s) : Mercey G , Verdelet T , Saint-Andre G , Gillon E , Wagner A , Baati R , Jean L , Nachon F , Renard PY
Ref : Chem Commun (Camb) , 47 :5295 , 2011
Abstract : Nerve agents are highly toxic organophosphorus compounds with strong inhibition potency against acetylcholinesterase (AChE). Herein, we describe two first extremely promising uncharged reactivators for poisoned human AChE with a superior or similar in vitro ability to reactivate the enzyme as compared to that of HI-6, obidoxime, TMB-4 and HLo-7.
ESTHER : Mercey_2011_Chem.Commun.(Camb)_47_5295
PubMedSearch : Mercey_2011_Chem.Commun.(Camb)_47_5295
PubMedID: 21451868

Title : A HTS assay for the detection of organophosphorus nerve agent scavengers - Louise-Leriche_2010_Chemistry_16_3510
Author(s) : Louise-Leriche L , Paunescu E , Saint-Andre G , Baati R , Romieu A , Wagner A , Renard PY
Ref : Chemistry , 16 :3510 , 2010
Abstract : A new pro-fluorescent probe aimed at a HTS assay of scavengers is able to selectively and efficiently cleave the P-S bond of organophosphorus nerve agents and by this provides non-toxic phosphonic acid has been designed and synthesised. The previously described pro-fluorescent probes were based on a conventional activated P-Oaryl bond cleavage, whereas our approach uses a self-immolative linker strategy that allows the detection of phosphonothioase activity with respect to a non-activated P-Salkyl bond. Further, we have also developed and optimised a high-throughput screening assay for the selection of decontaminants (chemical or biochemical scavengers) that could efficiently hydrolyse highly toxic V-type nerve agents. A preliminary screening, realised on a small alpha-nucleophile library, allowed us to identify some preliminary "hits", among which pyridinealdoximes, alpha-oxo oximes, hydroxamic acids and, less active but more original, amidoximes were the most promising. Their selective phosphonothioase activity has been further confirmed by using PhX as the substrate, and thus they offer new perspectives for the synthesis of more potent V nerve agent scavengers.
ESTHER : Louise-Leriche_2010_Chemistry_16_3510
PubMedSearch : Louise-Leriche_2010_Chemistry_16_3510
PubMedID: 20143367

Title : Formation and mobilization of neutral lipids in the yeast Saccharomyces cerevisiae - Wagner_2005_Biochem.Soc.Trans_33_1174
Author(s) : Wagner A , Daum G
Ref : Biochemical Society Transactions , 33 :1174 , 2005
Abstract : Since energy storage is a basic metabolic process, the synthesis of neutral lipids occurs in all kingdoms of life. The yeast Saccharomyces cerevisiae, widely accepted as a model eukaryotic cell, contains two classes of neutral lipids, namely STEs (steryl esters) and TAGs (triacylglycerols). TAGs are synthesized through two pathways governed by the acyl-CoA diacylglycerol acyltransferase Dga1p and the phospholipid diacylglycerol acyltransferase Lro1p. STEs are formed by two STE synthases Are1p and Are2p, two enzymes with overlapping function, which also catalyse TAG formation, although to a minor extent. Neutral lipids are stored in the so-called lipid particles and can be utilized for membrane formation under conditions of lipid depletion. For this purpose, storage lipids have to be mobilized by TAG lipases and STE hydrolases. A TAG lipase named Tgl3p was identified as a major yeast TAG hydrolytic enzyme in lipid particles. Recently, a new family of hydrolases was detected which is required for STE mobilization in S. cerevisiae. These enzymes, named Yeh1p, Yeh2p and Tgl1p, are paralogues of the mammalian acid lipase family. The role of these proteins in biosynthesis and mobilization of TAG and STE, and the regulation of these processes will be discussed in this minireview.
ESTHER : Wagner_2005_Biochem.Soc.Trans_33_1174
PubMedSearch : Wagner_2005_Biochem.Soc.Trans_33_1174
PubMedID: 16246075

Title : Human apolipoprotein AI mimetic peptides for the treatment of atherosclerosis - Navab_2003_Curr.Opin.Investig.Drugs_4_1100
Author(s) : Navab M , Anantharamaiah GM , Reddy ST , Van Lenten BJ , Hough G , Wagner A , Nakamura K , Garber DW , Datta G , Segrest JP , Hama S , Fogelman AM
Ref : Curr Opin Investig Drugs , 4 :1100 , 2003
Abstract : The effects of apolipoprotein (Apo) AI mimetic peptide synthesized from D- and L-amino acids on atherosclerotic lesion formation were investigated in low-density lipoprotein (LDL) receptor-deficient mice on a Western diet and in apoE null mice. In addition, their effects on the inflammatory changes induced in LDL-receptor mice fed a Western diet following influenza A infection were studied. When apolipoprotein AI mimetic peptides synthesized from either D- or L-amino acids were administered to LDL-receptor null mice, only peptides synthesized from D-amino acids were stable in the circulation and enhanced the ability of high-density lipoprotein (HDL) to protect LDL against oxidation. Administration of the peptide D-4F to LDL-receptor null mice and apoE null mice decreased lesion size. Additionally, in LDL receptor null mice after influenza infection, D-4F treatment increased plasma HDL levels and paraoxonase activity, and inhibited increased in LDL-cholesterol and peak levels of interleukin-6 post-infection. Injection of female mice with male macrophages, and subsequent measurement of the male 'sry' gene, revealed a marked increase in macrophage traffic into the aortic arch after infection that was prevented by administration of D-4F. This indicates that: (i) oral D-4F has powerful anti-atherosclerotic properties, and (ii) the loss of the anti-inflammatory properties of HDL after influenza infection in mice is associated with increased arterial macrophage traffic that can be prevented by administration of D-4F.
ESTHER : Navab_2003_Curr.Opin.Investig.Drugs_4_1100
PubMedSearch : Navab_2003_Curr.Opin.Investig.Drugs_4_1100
PubMedID: 14582455

Title : Mutants of luminous bacteria selected for bioluminescent toxicity tests - Wagner_1989_J.Biolumin.Chemilumin_4_342
Author(s) : Wagner A , Winkler U , Lummen P
Ref : J Biolumin Chemilumin , 4 :342 , 1989
Abstract : Mutants of the luminescent bacterial strain NRRL B-11177 were isolated with pleiotropic hypersensitivity towards hydrophobic antimicrobial agents. SDS-PAGE analyses of outer membrane proteins and lipopolysaccharides revealed that the outer membrane structure of the ahs-mutants was altered. QSAR analysis showed that the inhibitory effect of chloro-substituted phenols on bioluminescence of the ahs-mutants depended on their hydrophobicity. The effect of chlorinated phenols and detergents on bioluminescence was increased in the ahs-mutants. The potential use of these mutants in bioluminescent toxicity tests was discussed.
ESTHER : Wagner_1989_J.Biolumin.Chemilumin_4_342
PubMedSearch : Wagner_1989_J.Biolumin.Chemilumin_4_342
PubMedID: 2801221

Title : Some pharmacological properties of the false cholinergic transmitter acetylpyrrolidinecholine and its precursor pyrrolidinecholine - Kilbinger_1976_Naunyn.Schmiedebergs.Arch.Pharmacol_295_81
Author(s) : Kilbinger H , Wagner A , Zerban R
Ref : Naunyn Schmiedebergs Arch Pharmacol , 295 :81 , 1976
Abstract : The acetylchline analogue acetylpyrrolidinecholine as well as the choline analogue pyrrolidinecholine were synthesized and the cholinergic properties of both substances were investigated on the guinea-pig ileum, rat blood pressure and frog rectus abdominis muscle. Acetylpyrrolidinecholine was 3-5 times less potent than acetylcholine on the three preparations tested. The dose-response curves to acetylpyrrolidinecholine were shifted to the right in a parallel manner by atropine and (+)-tubocurarine. The dissociation constants for atropine and (+)-tubocurarine obtained with acetylpyrrolidinecholine as agonist were not different from those obtained with acetylcholine. This indicates that acetylpyrrolidinecholine specifically stimulates muscarine and nicotine receptors. Eserine potentiated the effects of acetylcholine more than those of acetylpyrrolidinecholine. Pyrrolidinecholine was only a weak agonist on the guinea-pig ileum. It caused a rise of rat blood pressure in doses higher than 10 mumol per rat. Neuromuscular transmission of the phrenic nerve-diaphragm preparation of the rat was not impaired during a 150 min incubation period with 1 mM pyrrolidinecholine. It is suggested that the possible formation and release of acetylpyrrolidinecholine as a false cholinergic transmitter does not modify neuromuscular transmission in skeletal muscle.
ESTHER : Kilbinger_1976_Naunyn.Schmiedebergs.Arch.Pharmacol_295_81
PubMedSearch : Kilbinger_1976_Naunyn.Schmiedebergs.Arch.Pharmacol_295_81
PubMedID: 187965