Author Report for: Wagner GNo contact information in database for Wagner G
Tyukhtenko S, Ma X, Rajarshi G, Karageorgos I, Anderson KW, Hudgens JW, Guo JJ, Nasr ML, Zvonok N and Makriyannis A <2 more author(s)> Tyukhtenko S, Ma X, Rajarshi G, Karageorgos I, Anderson KW, Hudgens JW, Guo JJ, Nasr ML, Zvonok N, Vemuri K, Wagner G, Makriyannis A (- 2) Ref: Sci Rep, 10:18531, 2020 : PubMed ESTHER: Tyukhtenko_2020_Sci.Rep_10_18531 PubMedSearch: Tyukhtenko 2020 Sci.Rep 10 18531 PubMedID: 33116203 Gene_locus related to this paper: human-MGLL Abstract Inhibition of human Monoacylglycerol Lipase (hMGL) offers a novel approach for treating neurological diseases. The design of inhibitors, targeting active-inactive conformational transitions of the enzyme, can be aided by understanding the interplay between structure and dynamics. Here, we report the effects of mutations within the catalytic triad on structure, conformational gating and dynamics of hMGL by combining kinetics, NMR, and HDX-MS data with metadynamics simulations. We found that point mutations alter delicate conformational equilibria between active and inactive states. HDX-MS reveals regions of the hMGL that become substantially more dynamic upon substitution of catalytic acid Asp-239 by alanine. These regions, located far from the catalytic triad, include not only loops but also rigid alpha-helixes and beta-strands, suggesting their involvement in allosteric regulation as channels for long-range signal transmission. The results identify the existence of a preorganized global communication network comprising of tertiary (residue-residue contacts) and quaternary (rigid-body contacts) networks that mediate robust, rapid intraprotein signal transmission. Catalytic Asp-239 controls hMGL allosteric communications and may be considered as an essential residue for the integration and transmission of information to enzymes' remote regions, in addition to its well-known role to facilitate Ser-122 activation. Our findings may assist in the identification of new druggable sites in hMGL. Title: Structure of a CGI-58 Motif Provides the Molecular Basis of Lipid Droplet Anchoring Boeszoermenyi A, Nagy HM, Arthanari H, Pillip CJ, Lindermuth H, Luna RE, Wagner G, Zechner R, Zangger K, Oberer M Ref: Journal of Biological Chemistry, 290:26361, 2015 : PubMed ESTHER: Boeszoermenyi_2015_J.Biol.Chem_290_26361 PubMedSearch: Boeszoermenyi 2015 J.Biol.Chem 290 26361 PubMedID: 26350461 Gene_locus related to this paper: human-ABHD5 Abstract Triacylglycerols (TGs) stored in lipid droplets (LDs) are hydrolyzed in a highly regulated metabolic process called lipolysis to free fatty acids that serve as energy substrates for beta-oxidation, precursors for membrane lipids and signaling molecules. Comparative gene identification-58 (CGI-58) stimulates the enzymatic activity of adipose triglyceride lipase (ATGL), which catalyzes the hydrolysis of TGs to diacylglycerols and free fatty acids. In adipose tissue, protein-protein interactions between CGI-58 and the LD coating protein perilipin 1 restrain the ability of CGI-58 to activate ATGL under basal conditions. Phosphorylation of perilipin 1 disrupts these interactions and mobilizes CGI-58 for the activation of ATGL. We have previously demonstrated that the removal of a peptide at the N terminus (residues 10-31) of CGI-58 abrogates CGI-58 localization to LDs and CGI-58-mediated activation of ATGL. Here, we show that this tryptophan-rich N-terminal peptide serves as an independent LD anchor, with its three tryptophans serving as focal points of the left (harboring Trp(21) and Trp(25)) and right (harboring Trp(29)) anchor arms. The solution state NMR structure of a peptide comprising the LD anchor bound to dodecylphosphocholine micelles as LD mimic reveals that the left arm forms a concise hydrophobic core comprising tryptophans Trp(21) and Trp(25) and two adjacent leucines. Trp(29) serves as the core of a functionally independent anchor arm. Consequently, simultaneous tryptophan alanine permutations in both arms abolish localization and activity of CGI-58 as opposed to tryptophan substitutions that occur in only one arm. Title: Dynamic thiolation-thioesterase structure of a non-ribosomal peptide synthetase Frueh DP, Arthanari H, Koglin A, Vosburg DA, Bennett AE, Walsh CT, Wagner G Ref: Nature, 454:903, 2008 : PubMed ESTHER: Frueh_2008_Nature_454_903 PubMedSearch: Frueh 2008 Nature 454 903 PubMedID: 18704088 Gene_locus related to this paper: ecoli-entf Abstract Non-ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) produce numerous secondary metabolites with various therapeutic/antibiotic properties. Like fatty acid synthases (FAS), these enzymes are organized in modular assembly lines in which each module, made of conserved domains, incorporates a given monomer unit into the growing chain. Knowledge about domain or module interactions may enable reengineering of this assembly line enzymatic organization and open avenues for the design of new bioactive compounds with improved therapeutic properties. So far, little structural information has been available on how the domains interact and communicate. This may be because of inherent interdomain mobility hindering crystallization, or because crystallized molecules may not represent the active domain orientations. In solution, the large size and internal dynamics of multidomain fragments (>35 kilodaltons) make structure determination by nuclear magnetic resonance a challenge and require advanced technologies. Here we present the solution structure of the apo-thiolation-thioesterase (T-TE) di-domain fragment of the Escherichia coli enterobactin synthetase EntF NRPS subunit. In the holoenzyme, the T domain carries the growing chain tethered to a 4'-phosphopantetheine whereas the TE domain catalyses hydrolysis and cyclization of the iron chelator enterobactin. The T-TE di-domain forms a compact but dynamic structure with a well-defined domain interface; the two active sites are at a suitable distance for substrate transfer from T to TE. We observe extensive interdomain and intradomain motions for well-defined regions and show that these are modulated by interactions with proteins that participate in the biosynthesis. The T-TE interaction described here provides a model for NRPS, PKS and FAS function in general as T-TE-like di-domains typically catalyse the last step in numerous assembly-line chain-termination machineries. Title: Structural basis for the selectivity of the external thioesterase of the surfactin synthetase Koglin A, Lohr F, Bernhard F, Rogov VV, Frueh DP, Strieter ER, Mofid MR, Guntert P, Wagner G and Dotsch V <2 more author(s)> Koglin A, Lohr F, Bernhard F, Rogov VV, Frueh DP, Strieter ER, Mofid MR, Guntert P, Wagner G, Walsh CT, Marahiel MA, Dotsch V (- 2) Ref: Nature, 454:907, 2008 : PubMed ESTHER: Koglin_2008_Nature_454_907 PubMedSearch: Koglin 2008 Nature 454 907 PubMedID: 18704089 Gene_locus related to this paper: bacsu-srf4 Abstract Non-ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) found in bacteria, fungi and plants use two different types of thioesterases for the production of highly active biological compounds. Type I thioesterases (TEI) catalyse the release step from the assembly line of the final product where it is transported from one reaction centre to the next as a thioester linked to a 4'-phosphopantetheine (4'-PP) cofactor that is covalently attached to thiolation (T) domains. The second enzyme involved in the synthesis of these secondary metabolites, the type II thioesterase (TEII), is a crucial repair enzyme for the regeneration of functional 4'-PP cofactors of holo-T domains of NRPS and PKS systems. Mispriming of 4'-PP cofactors by acetyl- and short-chain acyl-residues interrupts the biosynthetic system. This repair reaction is very important, because roughly 80% of CoA, the precursor of the 4'-PP cofactor, is acetylated in bacteria. Here we report the three-dimensional structure of a type II thioesterase from Bacillus subtilis free and in complex with a T domain. Comparison with structures of TEI enzymes shows the basis for substrate selectivity and the different modes of interaction of TEII and TEI enzymes with T domains. Furthermore, we show that the TEII enzyme exists in several conformations of which only one is selected on interaction with its native substrate, a modified holo-T domain. Title: The nucleotide sequence of Saccharomyces cerevisiae chromosome IV Jacq C, Alt-Morbe J, Andre B, Arnold W, Bahr A, Ballesta JP, Bargues M, Baron L, Becker A and Zaccaria P <126 more author(s)> Jacq C, Alt-Morbe J, Andre B, Arnold W, Bahr A, Ballesta JP, Bargues M, Baron L, Becker A, Biteau N, Blocker H, Blugeon C, Boskovic J, Brandt P, Bruckner M, Buitrago MJ, Coster F, Delaveau T, del Rey F, Dujon B, Eide LG, Garcia-Cantalejo JM, Goffeau A, Gomez-Peris AC, Granotier C, Hanemann V, Hankeln T, Hoheisel JD, Jager W, Jimenez A, Jonniaux JL, Kramer C, Kuster H, Laamanen P, Legros Y, Louis E, Muller-Rieker S, Monnet A, Moro M, Muller-Auer S, Nussbaumer B, Paricio N, Paulin L, Perea J, Perez-Alonso M, Perez-Ortin JE, Pohl TM, Prydz H, Purnelle B, Rasmussen SW, Remacha M, Revuelta JL, Rieger M, Salom D, Saluz HP, Saiz JE, Saren AM, Schafer M, Scharfe M, Schmidt ER, Schneider C, Scholler P, Schwarz S, Soler-Mira A, Urrestarazu LA, Verhasselt P, Vissers S, Voet M, Volckaert G, Wagner G, Wambutt R, Wedler E, Wedler H, Wolfl S, Harris DE, Bowman S, Brown D, Churcher CM, Connor R, Dedman K, Gentles S, Hamlin N, Hunt S, Jones L, McDonald S, Murphy L, Niblett D, Odell C, Oliver K, Rajandream MA, Richards C, Shore L, Walsh SV, Barrell BG, Dietrich FS, Mulligan J, Allen E, Araujo R, Aviles E, Berno A, Carpenter J, Chen E, Cherry JM, Chung E, Duncan M, Hunicke-Smith S, Hyman R, Komp C, Lashkari D, Lew H, Lin D, Mosedale D, Nakahara K, Namath A, Oefner P, Oh C, Petel FX, Roberts D, Schramm S, Schroeder M, Shogren T, Shroff N, Winant A, Yelton M, Botstein D, Davis RW, Johnston M, Hillier L, Riles L, Albermann K, Hani J, Heumann K, Kleine K, Mewes HW, Zollner A, Zaccaria P (- 126) Ref: Nature, 387:75, 1997 : PubMed ESTHER: Jacq_1997_Nature_387_75 PubMedSearch: Jacq 1997 Nature 387 75 PubMedID: 9169867 Gene_locus related to this paper: yeast-dlhh, yeast-ECM18, yeast-YDL109C, yeast-YDR428C, yeast-YDR444W Abstract The complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome IV has been determined. Apart from chromosome XII, which contains the 1-2 Mb rDNA cluster, chromosome IV is the longest S. cerevisiae chromosome. It was split into three parts, which were sequenced by a consortium from the European Community, the Sanger Centre, and groups from St Louis and Stanford in the United States. The sequence of 1,531,974 base pairs contains 796 predicted or known genes, 318 (39.9%) of which have been previously identified. Of the 478 new genes, 225 (28.3%) are homologous to previously identified genes and 253 (32%) have unknown functions or correspond to spurious open reading frames (ORFs). On average there is one gene approximately every two kilobases. Superimposed on alternating regional variations in G+C composition, there is a large central domain with a lower G+C content that contains all the yeast transposon (Ty) elements and most of the tRNA genes. Chromosome IV shares with chromosomes II, V, XII, XIII and XV some long clustered duplications which partly explain its origin. Title: alpha-Bungarotoxin, kappa-bungarotoxin, alpha-cobratoxin and erabutoxin-b do not affect [3H]acetylcholine release from the rat isolated left hemidiaphragm Apel C, Ricny J, Wagner G, Wessler I Ref: Naunyn Schmiedebergs Arch Pharmacol, 352:646, 1995 : PubMed ESTHER: Apel_1995_Naunyn.Schmiedebergs.Arch.Pharmacol_352_646 PubMedSearch: Apel 1995 Naunyn.Schmiedebergs.Arch.Pharmacol 352 646 PubMedID: 9053737 Abstract Endplate preparations of the rat left hemidiaphragm were incubated with [3H]choline to label neuronal transmitter stores. Nerve evoked release of newly-synthesized [3H]acetylcholine was measured in the absence of cholinesterase inhibitors to investigate whether snake venom neurotoxins by blocking presynaptic nicotinic autoreceptors affect evoked transmitter release. Contractions of the indirectly stimulated hemidiaphragm were recorded to characterize the blocking effect of alpha-neurotoxins at the post-synaptic nicotinic receptors. Neither the long chain neurotoxins alpha-cobratoxin (1 microgram ml-1) and alpha-bungarotoxin (5 microgram ml-1) nor the short chain neurotoxin erabutoxin-b (0.1, 1 and 10 micrograms ml-1) affected the nerve-evoked release of [3H]acetylcholine. kappa-Bungarotoxin (1 and 5 micrograms ml-1), a toxin preferentially blocking neuronal nicotinic receptors, did also not affect evoked [3H]acetylcholine release, whereas (+)-tubocurarine (1 microM) under identical conditions reduced the release by about 50%. alpha-Bungarotoxin, alpha-cobratoxin and erabutoxin-b concentration-dependently (0.01-0.6 micrograms ml-1) inhibited nerve-evoked contractions of the hemidiaphragm. All neurotoxins except erabutoxin-b enhanced the basal tritium efflux immediately when applied to the endplate preparation or to a non-innervated muscle strip labelled with [3H]choline. This effect was attributed to an enhanced efflux of [3H]phosphorylcholine, whereas the efflux of [3H]choline and [3H]acetylcholine was not affected. It is concluded that the alpha-neurotoxins and kappa-bungarotoxin do not block presynaptic nicotinic receptors of motor nerves. These nicotinic autoreceptors differ from nicotinic receptors localized at the muscle membrane and at autonomic ganglia. Title: Complete DNA sequence of yeast chromosome II Feldmann H, Aigle M, Aljinovic G, Andre B, Baclet MC, Barthe C, Baur A, Becam AM, Biteau N and Schaaff-Gerstenschlger I <91 more author(s)> Feldmann H, Aigle M, Aljinovic G, Andre B, Baclet MC, Barthe C, Baur A, Becam AM, Biteau N, Boles E, Brandt T, Brendel M, Bruckner M, Bussereau F, Christiansen C, Contreras R, Crouzet M, Cziepluch C, Demolis N, Delaveau T, Doignon F, Domdey H, Dusterhus S, Dubois E, Dujon B, El Bakkoury M, Entian KD, Feurmann M, Fiers W, Fobo GM, Fritz C, Gassenhuber H, Glandsdorff N, Goffeau A, Grivell LA, de Haan M, Hein C, Herbert CJ, Hollenberg CP, Holmstrom K, Jacq C, Jacquet M, Jauniaux JC, Jonniaux JL, Kallesoe T, Kiesau P, Kirchrath L, Kotter P, Korol S, Liebl S, Logghe M, Lohan AJ, Louis EJ, Li ZY, Maat MJ, Mallet L, Mannhaupt G, Messenguy F, Miosga T, Molemans F, Muller S, Nasr F, Obermaier B, Perea J, Pierard A, Piravandi E, Pohl FM, Pohl TM, Potier S, Proft M, Purnelle B, Ramezani Rad M, Rieger M, Rose M, Schaaff-Gerstenschlager I, Scherens B, Schwarzlose C, Skala J, Slonimski PP, Smits PH, Souciet JL, Steensma HY, Stucka R, Urrestarazu A, van der Aart QJ, van Dyck L, Vassarotti A, Vetter I, Vierendeels F, Vissers S, Wagner G, de Wergifosse P, Wolfe KH, Zagulski M, Zimmermann FK, Mewes HW, Kleine K, Dsterhus S, Mller S, Pirard A, Schaaff-Gerstenschlger I (- 91) Ref: EMBO Journal, 13:5795, 1994 : PubMed ESTHER: Feldmann_1994_EMBO.J_13_5795 PubMedSearch: Feldmann 1994 EMBO.J 13 5795 PubMedID: 7813418 Gene_locus related to this paper: yeast-LDH1, yeast-MCFS2, yeast-yby9 Abstract In the framework of the EU genome-sequencing programmes, the complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome II (807 188 bp) has been determined. At present, this is the largest eukaryotic chromosome entirely sequenced. A total of 410 open reading frames (ORFs) were identified, covering 72% of the sequence. Similarity searches revealed that 124 ORFs (30%) correspond to genes of known function, 51 ORFs (12.5%) appear to be homologues of genes whose functions are known, 52 others (12.5%) have homologues the functions of which are not well defined and another 33 of the novel putative genes (8%) exhibit a degree of similarity which is insufficient to confidently assign function. Of the genes on chromosome II, 37-45% are thus of unpredicted function. Among the novel putative genes, we found several that are related to genes that perform differentiated functions in multicellular organisms of are involved in malignancy. In addition to a compact arrangement of potential protein coding sequences, the analysis of this chromosome confirmed general chromosome patterns but also revealed particular novel features of chromosomal organization. Alternating regional variations in average base composition correlate with variations in local gene density along chromosome II, as observed in chromosomes XI and III. We propose that functional ARS elements are preferably located in the AT-rich regions that have a spacing of approximately 110 kb. Similarly, the 13 tRNA genes and the three Ty elements of chromosome II are found in AT-rich regions. In chromosome II, the distribution of coding sequences between the two strands is biased, with a ratio of 1.3:1. An interesting aspect regarding the evolution of the eukaryotic genome is the finding that chromosome II has a high degree of internal genetic redundancy, amounting to 16% of the coding capacity. Title: Suppression by cholinesterase inhibition of a Ca(2+)-independent efflux of [3H]acetylcholine from the neuromuscular junction of the isolated rat diaphragm Wessler I, Wagner G, Walczok A Ref: European Journal of Pharmacology, 221:371, 1992 : PubMed ESTHER: Wessler_1992_Eur.J.Pharmacol_221_371 PubMedSearch: Wessler 1992 Eur.J.Pharmacol 221 371 PubMedID: 1426013 Abstract Endplate preparations of the left rat hemidiaphragm were incubated with [3H]choline to label neuronal acetylcholine stores. Elevation of the concentration (13.5-135 mmol/l) of extracellular potassium chloride (KCl) stimulated the release of [3H]acetylcholine in a concentration-dependent manner. KCl (27 mmol/l) still caused a significant efflux of [3H]acetylcholine in a Ca(2+)-free medium. Inhibitors of cholinesterase (physostigmine, diisopropylfluorophosphate) suppressed by 80% this Ca(2+)-independent efflux of [3H]acetylcholine. Vesamicol (10 mumol/l), the blocker of the vesicular acetylcholine carrier, also suppressed the stimulated, Ca(2+)-independent efflux of [3H]acetylcholine. The inhibitory effect of physostigmine was not prevented by muscarine or nicotine receptor antagonists, but the inhibitory effect was lost when the stimulus strength was increased (81 mmol/l KCl). The present experiments showed cholinesterase inhibition to suppress a Ca(2+)-independent efflux of [3H]acetylcholine, probably by interference with a membrane-bound acetylcholine carrier. | |||||||
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