Elias M

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Full name : Elias Mikael

First name : Mikael

Mail : Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100

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Country : Israel

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References (26)

Title : Engineering acyl-homoserine lactone-interfering enzymes toward bacterial control - Billot_2020_J.Biol.Chem_295_12993
Author(s) : Billot R , Plener L , Jacquet P , Elias M , Chabriere E , Daude D
Ref : Journal of Biological Chemistry , 295 :12993 , 2020
Abstract : Enzymes able to degrade or modify acyl-homoserine lactones (AHLs) have drawn considerable interest for their ability to interfere with the bacterial communication process referred to as quorum sensing. Many proteobacteria use AHL to coordinate virulence and biofilm formation in a cell density-dependent manner; thus, AHL-interfering enzymes constitute new promising antimicrobial candidates. Among these, lactonases and acylases have been particularly studied. These enzymes have been isolated from various bacterial, archaeal, or eukaryotic organisms and have been evaluated for their ability to control several pathogens. Engineering studies on these enzymes were carried out and successfully modulated their capacity to interact with specific AHL, increase their catalytic activity and stability, or enhance their biotechnological potential. In this review, special attention is paid to the screening, engineering, and applications of AHL-modifying enzymes. Prospects and future opportunities are also discussed with a view to developing potent candidates for bacterial control.
ESTHER : Billot_2020_J.Biol.Chem_295_12993
PubMedSearch : Billot_2020_J.Biol.Chem_295_12993
PubMedID: 32690609

Title : Biotechnological applications of quorum quenching enzymes - Bzdrenga_2017_Chem.Biol.Interact_267_104
Author(s) : Bzdrenga J , Daude D , Remy B , Jacquet P , Plener L , Elias M , Chabriere E
Ref : Chemico-Biological Interactions , 267 :104 , 2017
Abstract : Numerous bacteria use quorum sensing (QS) to synchronize their behavior and monitor their population density. They use signaling molecules known as autoinducers (AI's) that are synthesized and secreted into their local environment to regulate QS-dependent gene expression. Among QS-regulated pathways, biofilm formation and virulence factor secretion are particularly problematic as they are involved in surface-attachment, antimicrobial agent resistance, toxicity, and pathogenicity. Targeting QS represents a promising strategy to inhibit undesirable bacterial traits. This strategy, referred to as quorum quenching (QQ), includes QS-inhibitors and QQ enzymes. These approaches are appealing because they do not directly challenge bacterial survival, and consequently selection pressure may be low, yielding a lower occurrence of resistance. QQ enzymes are particularly promising because they act extracellularly to degrade AI's and can be used in catalytic quantities. This review draws an overview of QQ enzyme related applications, covering several economically important fields such as agriculture, aquaculture, biofouling and health issues. Finally, the possibility of resistance mechanism occurrence to QQ strategies is discussed.
ESTHER : Bzdrenga_2017_Chem.Biol.Interact_267_104
PubMedSearch : Bzdrenga_2017_Chem.Biol.Interact_267_104
PubMedID: 27223408

Title : [Decontamination of organophosphorus compounds: Towards new alternatives] - Poirier_2017_Ann.Pharm.Fr_75_209
Author(s) : Poirier L , Jacquet P , Elias M , Daude D , Chabriere E
Ref : Ann Pharm Fr , 75 :209 , 2017
Abstract : Organophosphorus coumpounds (OP) are toxic chemicals mainly used for agricultural purpose such as insecticides and were also developed and used as warfare nerve agents. OP are inhibitors of acetylcholinesterase, a key enzyme involved in the regulation of the central nervous system. Chemical, physical and biological approaches have been considered to decontaminate OP. This review summarizes the current and emerging strategies that are investigated to tackle this issue with a special emphasis on enzymatic remediation methods. During the last decade, many studies have been dedicated to the development of biocatalysts for OP removal. Among these, recent reports have pointed out the promising enzyme SsoPox isolated from the archaea Sulfolobus solfataricus. Considering both its intrinsic stability and activity, this hyperthermostable enzyme is highly appealing for the decontamination of OP.
ESTHER : Poirier_2017_Ann.Pharm.Fr_75_209
PubMedSearch : Poirier_2017_Ann.Pharm.Fr_75_209
PubMedID: 28267954

Title : Similar Active Sites and Mechanisms Do Not Lead to Cross-Promiscuity in Organophosphate Hydrolysis: Implications for Biotherapeutic Engineering - Purg_2017_J.Am.Chem.Soc_139_17533
Author(s) : Purg M , Elias M , Kamerlin SCL
Ref : Journal of the American Chemical Society , 139 :17533 , 2017
Abstract : Organophosphate hydrolases are proficient catalysts of the breakdown of neurotoxic organophosphates and have great potential as both biotherapeutics for treating acute organophosphate toxicity and as bioremediation agents. However, proficient organophosphatases such as serum paraoxonase 1 (PON1) and the organophosphate-hydrolyzing lactonase SsoPox are unable to hydrolyze bulkyorganophosphates with challenging leaving groups such as diisopropyl fluorophosphate (DFP) or venomous agent X, creating a major challenge for enzyme design. Curiously, despite their mutually exclusive substrate specificities, PON1 and diisopropyl fluorophosphatase (DFPase) have essentially identical active sites and tertiary structures. In the present work, we use empirical valence bond simulations to probe the catalytic mechanism of DFPase as well as temperature, pH, and mutational effects, demonstrating that DFPase and PON1 also likely utilize identical catalytic mechanisms to hydrolyze their respective substrates. However, detailed examination of both static structures and dynamical simulations demonstrates subtle but significant differences in the electrostatic properties and solvent penetration of the two active sites and, most critically, the role of residues that make no direct contact with either substrate in acting as "specificity switches" between the two enzymes. Specifically, we demonstrate that key residues that are structurally and functionally critical for the paraoxonase activity of PON1 prevent it from being able to hydrolyze DFP with its fluoride leaving group. These insights expand our understanding of the drivers of the evolution of divergent substrate specificity in enzymes with identical active sites and guide the future design of organophosphate hydrolases that hydrolyze compounds with challenging leaving groups.
ESTHER : Purg_2017_J.Am.Chem.Soc_139_17533
PubMedSearch : Purg_2017_J.Am.Chem.Soc_139_17533
PubMedID: 29113434

Title : Harnessing hyperthermostable lactonase from Sulfolobus solfataricus for biotechnological applications - Remy_2016_Sci.Rep_6_37780
Author(s) : Remy B , Plener L , Poirier L , Elias M , Daude D , Chabriere E
Ref : Sci Rep , 6 :37780 , 2016
Abstract : Extremozymes have gained considerable interest as they could meet industrial requirements. Among these, SsoPox is a hyperthermostable enzyme isolated from the archaeon Sulfolobus solfataricus. This enzyme is a lactonase catalyzing the hydrolysis of acyl-homoserine lactones; these molecules are involved in Gram-negative bacterial communication referred to as quorum sensing. SsoPox exhibits promiscuous phosphotriesterase activity for the degradation of organophosphorous chemicals including insecticides and chemical warfare agents. Owing to its bi-functional catalytic abilities as well as its intrinsic stability, SsoPox is appealing for many applications, having potential uses in the agriculture, defense, food and health industries. Here we investigate the biotechnological properties of the mutant SsoPox-W263I, a variant with increased lactonase and phosphotriesterase activities. We tested enzyme resistance against diverse process-like and operating conditions such as heat resistance, contact with organic solvents, sterilization, storage and immobilization. Bacterial secreted materials from both Gram-negative and positive bacteria were harmless on SsoPox-W263I activity and could reactivate heat-inactivated enzyme. SsoPox showed resistance to harsh conditions demonstrating that it is an extremely attractive enzyme for many applications. Finally, the potential of SsoPox-W263I to be active at subzero temperature is highlighted and discussed in regards to the common idea that hyperthermophile enzymes are nearly inactive at low temperatures.
ESTHER : Remy_2016_Sci.Rep_6_37780
PubMedSearch : Remy_2016_Sci.Rep_6_37780
PubMedID: 27876889

Title : Current and emerging strategies for organophosphate decontamination: special focus on hyperstable enzymes - Jacquet_2016_Environ.Sci.Pollut.Res.Int_23_8200
Author(s) : Jacquet P , Daude D , Bzdrenga J , Masson P , Elias M , Chabriere E
Ref : Environ Sci Pollut Res Int , 23 :8200 , 2016
Abstract : Organophosphorus chemicals are highly toxic molecules mainly used as pesticides. Some of them are banned warfare nerve agents. These compounds are covalent inhibitors of acetylcholinesterase, a key enzyme in central and peripheral nervous systems. Numerous approaches, including chemical, physical, and biological decontamination, have been considered for developing decontamination methods against organophosphates (OPs). This work is an overview of both validated and emerging strategies for the protection against OP pollution with special attention to the use of decontaminating enzymes. Considerable efforts have been dedicated during the past decades to the development of efficient OP degrading biocatalysts. Among these, the promising biocatalyst SsoPox isolated from the archaeon Sulfolobus solfataricus is emphasized in the light of recently published results. This hyperthermostable enzyme appears to be particularly attractive for external decontamination purposes with regard to both its catalytic and stability properties.
ESTHER : Jacquet_2016_Environ.Sci.Pollut.Res.Int_23_8200
PubMedSearch : Jacquet_2016_Environ.Sci.Pollut.Res.Int_23_8200
PubMedID: 26832878

Title : Catalytic metal ion rearrangements underline promiscuity and evolvability of a metalloenzyme - Ben-David_2013_J.Mol.Biol_425_1028
Author(s) : Ben-David M , Wieczorek G , Elias M , Silman I , Sussman JL , Tawfik DS
Ref : Journal of Molecular Biology , 425 :1028 , 2013
Abstract : Although largely deemed as structurally conserved, catalytic metal ion sites can rearrange, thereby contributing to enzyme evolvability. Here, we show that in paraoxonase-1, a lipo-lactonase, catalytic promiscuity and divergence into an organophosphate hydrolase are correlated with an alternative mode of the catalytic Ca(2+). We describe the crystal structures of active-site mutants bearing mutations at position 115. The histidine at this position acts as a base to activate the lactone-hydrolyzing water molecule. Mutations to Trp or Gln indeed diminish paraoxonase-1's lactonase activity; however, the promiscuous organophosphate hydrolase activity is enhanced. The structures reveal a 1.8-A upward displacement towards the enzyme's surface of the catalytic Ca(2+) in the His115 mutants and configurational changes in the ligating side chains and water molecules, relative to the wild-type enzyme. Biochemical analysis and molecular dynamics simulations suggest that this alternative, upward metal mode mediates the promiscuous hydrolysis of organophosphates. The upward Ca(2+) mode observed in the His115 mutants also appears to mediate the wild type's paraoxonase activity. However, whereas the upward mode dominates in the Trp115 mutant, it is scarcely populated in wild type. Thus, the plasticity of active-site metal ions may permit alternative, latent, promiscuous activities and also provide the basis for the divergence of new enzymatic functions.
ESTHER : Ben-David_2013_J.Mol.Biol_425_1028
PubMedSearch : Ben-David_2013_J.Mol.Biol_425_1028
PubMedID: 23318950

Title : Crystallization and preliminary X-ray diffraction analysis of the organophosphorus hydrolase OPHC2 from Pseudomonas pseudoalcaligenes - Gotthard_2013_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_69_73
Author(s) : Gotthard G , Hiblot J , Gonzalez D , Chabriere E , Elias M
Ref : Acta Crystallographica Sect F Struct Biol Cryst Commun , 69 :73 , 2013
Abstract : Enzymes that are capable of degrading neurotoxic organophosphorus compounds are of increasing interest because of the lack of efficient and clean methods for their removal. Recently, a novel organophosphorus hydrolase belonging to the metallo-beta-lactamase superfamily was identified and isolated from the mesophilic bacterium Pseudomonas pseudoalcaligenes. This enzyme, named OPHC2, is endowed with significant thermal and pH stability, making it an appealing candidate for engineering studies to develop an efficient organophosphorus biodecontaminant. Combined with biochemical studies, structural information will help decipher the catalytic mechanism of organophosphorus hydrolysis by OPHC2 and identify the residues involved in its substrate specificity. Here, the expression, purification, crystallization and X-ray data collection at 2.1 A resolution of OPHC2 are presented.
ESTHER : Gotthard_2013_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_69_73
PubMedSearch : Gotthard_2013_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_69_73
PubMedID: 23295492

Title : Genome structure and metabolic features in the red seaweed Chondrus crispus shed light on evolution of the Archaeplastida - Collen_2013_Proc.Natl.Acad.Sci.U.S.A_110_5247
Author(s) : Collen J , Porcel B , Carre W , Ball SG , Chaparro C , Tonon T , Barbeyron T , Michel G , Noel B , Valentin K , Elias M , Artiguenave F , Arun A , Aury JM , Barbosa-Neto JF , Bothwell JH , Bouget FY , Brillet L , Cabello-Hurtado F , Capella-Gutierrez S , Charrier B , Cladiere L , Cock JM , Coelho SM , Colleoni C , Czjzek M , Da Silva C , Delage L , Denoeud F , Deschamps P , Dittami SM , Gabaldon T , Gachon CM , Groisillier A , Herve C , Jabbari K , Katinka M , Kloareg B , Kowalczyk N , Labadie K , LeBlanc C , Lopez PJ , McLachlan DH , Meslet-Cladiere L , Moustafa A , Nehr Z , Nyvall Collen P , Panaud O , Partensky F , Poulain J , Rensing SA , Rousvoal S , Samson G , Symeonidi A , Weissenbach J , Zambounis A , Wincker P , Boyen C
Ref : Proc Natl Acad Sci U S A , 110 :5247 , 2013
Abstract : Red seaweeds are key components of coastal ecosystems and are economically important as food and as a source of gelling agents, but their genes and genomes have received little attention. Here we report the sequencing of the 105-Mbp genome of the florideophyte Chondrus crispus (Irish moss) and the annotation of the 9,606 genes. The genome features an unusual structure characterized by gene-dense regions surrounded by repeat-rich regions dominated by transposable elements. Despite its fairly large size, this genome shows features typical of compact genomes, e.g., on average only 0.3 introns per gene, short introns, low median distance between genes, small gene families, and no indication of large-scale genome duplication. The genome also gives insights into the metabolism of marine red algae and adaptations to the marine environment, including genes related to halogen metabolism, oxylipins, and multicellularity (microRNA processing and transcription factors). Particularly interesting are features related to carbohydrate metabolism, which include a minimalistic gene set for starch biosynthesis, the presence of cellulose synthases acquired before the primary endosymbiosis showing the polyphyly of cellulose synthesis in Archaeplastida, and cellulases absent in terrestrial plants as well as the occurrence of a mannosylglycerate synthase potentially originating from a marine bacterium. To explain the observations on genome structure and gene content, we propose an evolutionary scenario involving an ancestral red alga that was driven by early ecological forces to lose genes, introns, and intergenetic DNA; this loss was followed by an expansion of genome size as a consequence of activity of transposable elements.
ESTHER : Collen_2013_Proc.Natl.Acad.Sci.U.S.A_110_5247
PubMedSearch : Collen_2013_Proc.Natl.Acad.Sci.U.S.A_110_5247
PubMedID: 23503846
Gene_locus related to this paper: chocr-r7qut2 , chocr-r7qfm4 , chocr-r7qf11

Title : Catalytic versatility and backups in enzyme active sites: the case of serum paraoxonase 1 - Ben-David_2012_J.Mol.Biol_418_181
Author(s) : Ben-David M , Elias M , Filippi JJ , Dunach E , Silman I , Sussman JL , Tawfik DS
Ref : Journal of Molecular Biology , 418 :181 , 2012
Abstract : The origins of enzyme specificity are well established. However, the molecular details underlying the ability of a single active site to promiscuously bind different substrates and catalyze different reactions remain largely unknown. To better understand the molecular basis of enzyme promiscuity, we studied the mammalian serum paraoxonase 1 (PON1) whose native substrates are lipophilic lactones. We describe the crystal structures of PON1 at a catalytically relevant pH and of its complex with a lactone analogue. The various PON1 structures and the analysis of active-site mutants guided the generation of docking models of the various substrates and their reaction intermediates. The models suggest that promiscuity is driven by coincidental overlaps between the reactive intermediate for the native lactonase reaction and the ground and/or intermediate states of the promiscuous reactions. This overlap is also enabled by different active-site conformations: the lactonase activity utilizes one active-site conformation whereas the promiscuous phosphotriesterase activity utilizes another. The hydrolysis of phosphotriesters, and of the aromatic lactone dihydrocoumarin, is also driven by an alternative catalytic mode that uses only a subset of the active-site residues utilized for lactone hydrolysis. Indeed, PON1's active site shows a remarkable level of networking and versatility whereby multiple residues share the same task and individual active-site residues perform multiple tasks (e.g., binding the catalytic calcium and activating the hydrolytic water). Overall, the coexistence of multiple conformations and alternative catalytic modes within the same active site underlines PON1's promiscuity and evolutionary potential.
ESTHER : Ben-David_2012_J.Mol.Biol_418_181
PubMedSearch : Ben-David_2012_J.Mol.Biol_418_181
PubMedID: 22387469

Title : Divergence and convergence in enzyme evolution: parallel evolution of paraoxonases from quorum-quenching lactonases - Elias_2012_J.Biol.Chem_287_11
Author(s) : Elias M , Tawfik DS
Ref : Journal of Biological Chemistry , 287 :11 , 2012
Abstract : We discuss the basic features of divergent versus convergent evolution and of the common scenario of parallel evolution. The example of quorum-quenching lactonases is subsequently described. Three different quorum-quenching lactonase families are known, and they belong to three different superfamilies. Their key active-site architectures have converged and are strikingly similar. Curiously, a promiscuous organophosphate hydrolase activity is observed in all three families. We describe the structural and mechanistic features that underline this converged promiscuity and how this promiscuity drove the parallel divergence of organophosphate hydrolases within these lactonase families by either natural or laboratory evolution.
ESTHER : Elias_2012_J.Biol.Chem_287_11
PubMedSearch : Elias_2012_J.Biol.Chem_287_11
PubMedID: 22069329

Title : Algal genomes reveal evolutionary mosaicism and the fate of nucleomorphs - Curtis_2012_Nature_492_59
Author(s) : Curtis BA , Tanifuji G , Burki F , Gruber A , Irimia M , Maruyama S , Arias MC , Ball SG , Gile GH , Hirakawa Y , Hopkins JF , Kuo A , Rensing SA , Schmutz J , Symeonidi A , Elias M , Eveleigh RJ , Herman EK , Klute MJ , Nakayama T , Obornik M , Reyes-Prieto A , Armbrust EV , Aves SJ , Beiko RG , Coutinho P , Dacks JB , Durnford DG , Fast NM , Green BR , Grisdale CJ , Hempel F , Henrissat B , Hoppner MP , Ishida K , Kim E , Koreny L , Kroth PG , Liu Y , Malik SB , Maier UG , McRose D , Mock T , Neilson JA , Onodera NT , Poole AM , Pritham EJ , Richards TA , Rocap G , Roy SW , Sarai C , Schaack S , Shirato S , Slamovits CH , Spencer DF , Suzuki S , Worden AZ , Zauner S , Barry K , Bell C , Bharti AK , Crow JA , Grimwood J , Kramer R , Lindquist E , Lucas S , Salamov A , McFadden GI , Lane CE , Keeling PJ , Gray MW , Grigoriev IV , Archibald JM
Ref : Nature , 492 :59 , 2012
Abstract : Cryptophyte and chlorarachniophyte algae are transitional forms in the widespread secondary endosymbiotic acquisition of photosynthesis by engulfment of eukaryotic algae. Unlike most secondary plastid-bearing algae, miniaturized versions of the endosymbiont nuclei (nucleomorphs) persist in cryptophytes and chlorarachniophytes. To determine why, and to address other fundamental questions about eukaryote-eukaryote endosymbiosis, we sequenced the nuclear genomes of the cryptophyte Guillardia theta and the chlorarachniophyte Bigelowiella natans. Both genomes have >21,000 protein genes and are intron rich, and B. natans exhibits unprecedented alternative splicing for a single-celled organism. Phylogenomic analyses and subcellular targeting predictions reveal extensive genetic and biochemical mosaicism, with both host- and endosymbiont-derived genes servicing the mitochondrion, the host cell cytosol, the plastid and the remnant endosymbiont cytosol of both algae. Mitochondrion-to-nucleus gene transfer still occurs in both organisms but plastid-to-nucleus and nucleomorph-to-nucleus transfers do not, which explains why a small residue of essential genes remains locked in each nucleomorph.
ESTHER : Curtis_2012_Nature_492_59
PubMedSearch : Curtis_2012_Nature_492_59
PubMedID: 23201678
Gene_locus related to this paper: guith-l1i9i5 , guith-l1k167 , guitc-l1jmn9

Title : Comparative genomics of the social amoebae Dictyostelium discoideum and Dictyostelium purpureum - Sucgang_2011_Genome.Biol_12_R20.1
Author(s) : Sucgang R , Kuo A , Tian X , Salerno W , Parikh A , Feasley CL , Dalin E , Tu H , Huang E , Barry K , Lindquist E , Shapiro H , Bruce D , Schmutz J , Salamov A , Fey P , Gaudet P , Anjard C , Babu MM , Basu S , Bushmanova Y , van der Wel H , Katoh-Kurasawa M , Dinh C , Coutinho PM , Saito T , Elias M , Schaap P , Kay RR , Henrissat B , Eichinger L , Rivero F , Putnam NH , West CM , Loomis WF , Chisholm RL , Shaulsky G , Strassmann JE , Queller DC , Kuspa A , Grigoriev IV
Ref : Genome Biol , 12 :R20 , 2011
Abstract : BACKGROUND: The social amoebae (Dictyostelia) are a diverse group of Amoebozoa that achieve multicellularity by aggregation and undergo morphogenesis into fruiting bodies with terminally differentiated spores and stalk cells. There are four groups of dictyostelids, with the most derived being a group that contains the model species Dictyostelium discoideum.
RESULTS: We have produced a draft genome sequence of another group dictyostelid, Dictyostelium purpureum, and compare it to the D. discoideum genome. The assembly (8.41 x coverage) comprises 799 scaffolds totaling 33.0 Mb, comparable to the D. discoideum genome size. Sequence comparisons suggest that these two dictyostelids shared a common ancestor approximately 400 million years ago. In spite of this divergence, most orthologs reside in small clusters of conserved synteny. Comparative analyses revealed a core set of orthologous genes that illuminate dictyostelid physiology, as well as differences in gene family content. Interesting patterns of gene conservation and divergence are also evident, suggesting function differences; some protein families, such as the histidine kinases, have undergone little functional change, whereas others, such as the polyketide synthases, have undergone extensive diversification. The abundant amino acid homopolymers encoded in both genomes are generally not found in homologous positions within proteins, so they are unlikely to derive from ancestral DNA triplet repeats. Genes involved in the social stage evolved more rapidly than others, consistent with either relaxed selection or accelerated evolution due to social conflict.
CONCLUSIONS: The findings from this new genome sequence and comparative analysis shed light on the biology and evolution of the Dictyostelia.
ESTHER : Sucgang_2011_Genome.Biol_12_R20.1
PubMedSearch : Sucgang_2011_Genome.Biol_12_R20.1
PubMedID: 21356102
Gene_locus related to this paper: dicpu-f0z7q0 , dicpu-f0z822 , dicpu-f0zfi0 , dicpu-f0zjs1 , dicpu-f0zks4 , dicpu-f0zmm3 , dicpu-f0zmm8 , dicpu-f0zmm9 , dicpu-f0zni7 , dicpu-f0znl3 , dicpu-f0zq90 , dicpu-f0zvn5 , dicpu-f0zxa4 , dicpu-f0zyf9 , dicpu-f1a3n5 , dicpu-f1a5b4 , dicpu-f1a269 , dicpu-f1a615 , dicpu-f0ztw9 , dicpu-f0zri3 , dicpu-f0zys7

Title : Crystallization and preliminary X-ray diffraction analysis of the hyperthermophilic Sulfolobus islandicus lactonase - Gotthard_2011_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_67_354
Author(s) : Gotthard G , Hiblot J , Elias M , Chabriere E
Ref : Acta Crystallographica Sect F Struct Biol Cryst Commun , 67 :354 , 2011
Abstract : Phosphotriesterase-like lactonases (PLLs) constitute an interesting family of enzymes that are of paramount interest in biotechnology with respect to their catalytic functions. As natural lactonases, they may act against pathogens such as Pseudomonas aeruginosa by shutting down their quorum-sensing system (quorum quenching) and thus decreasing pathogen virulence. Owing to their promiscuous phosphotriesterase activity, which can inactivate toxic organophosphorus compounds such as pesticides and nerve agents, they are equally appealing as potent bioscavengers. A new representative of the PLL family has been identified (SisPox) and its gene was cloned from the hyperthermophilic archeon Sulfolobus islandicus. Owing to its hyperthermostable architecture, SisPox appears to be a good candidate for engineering studies. Here, production, purification, crystallization conditions and data collection to 2.34A resolution are reported for this lactonase from the hyperthermophilic S. islandicus.
ESTHER : Gotthard_2011_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_67_354
PubMedSearch : Gotthard_2011_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_67_354
PubMedID: 21393842

Title : Directed evolution of sulfotransferases and paraoxonases by ancestral libraries - Alcolombri_2011_J.Mol.Biol_411_837
Author(s) : Alcolombri U , Elias M , Tawfik DS
Ref : Journal of Molecular Biology , 411 :837 , 2011
Abstract : Large libraries of randomly mutated genes are applied in directed evolution experiments in order to obtain sufficient variability. These libraries, however, contain mostly inactive variants, and the very low frequency of improved variants can only be isolated by high-throughput screening. Small but efficient libraries comprise an attractive alternative. Here, we describe the application of ancestral libraries-libraries based on mutations predicted by phylogenetic analysis and ancestral inference. We designed and constructed such libraries using serum paraoxonases and cytosolic sulfotransferases (SULTs) as model enzymes. Both of these enzyme families exhibit a range of activities in drug metabolism and detoxification of xenobiotics. The ancestral serum paraoxonase and SULT libraries were screened by low-throughput means, including HPLC, using substrates and/or reactions with which all family members exhibit low activity. The libraries showed a remarkably high frequency of highly polymorphic and functionally diverse variants. Screening of as few as 300 variants enabled the isolation of mutants with up to 50-fold higher activity than the starting point enzyme. Structural and kinetic characterizations of an evolved SULT variant show how few ancestral mutations reshaped the active site and modulated the enzyme's specificity. Ancestral libraries therefore comprise a means of focusing diversity to positions and mutations that readily trigger changes in substrate and/or reaction specificity, thereby facilitating the isolation of new enzyme variants for a variety of different substrates and reactions by medium-throughput or even low-throughput screens.
ESTHER : Alcolombri_2011_J.Mol.Biol_411_837
PubMedSearch : Alcolombri_2011_J.Mol.Biol_411_837
PubMedID: 21723874

Title : The Selaginella genome identifies genetic changes associated with the evolution of vascular plants - Banks_2011_Science_332_960
Author(s) : Banks JA , Nishiyama T , Hasebe M , Bowman JL , Gribskov M , dePamphilis C , Albert VA , Aono N , Aoyama T , Ambrose BA , Ashton NW , Axtell MJ , Barker E , Barker MS , Bennetzen JL , Bonawitz ND , Chapple C , Cheng C , Correa LG , Dacre M , DeBarry J , Dreyer I , Elias M , Engstrom EM , Estelle M , Feng L , Finet C , Floyd SK , Frommer WB , Fujita T , Gramzow L , Gutensohn M , Harholt J , Hattori M , Heyl A , Hirai T , Hiwatashi Y , Ishikawa M , Iwata M , Karol KG , Koehler B , Kolukisaoglu U , Kubo M , Kurata T , Lalonde S , Li K , Li Y , Litt A , Lyons E , Manning G , Maruyama T , Michael TP , Mikami K , Miyazaki S , Morinaga S , Murata T , Mueller-Roeber B , Nelson DR , Obara M , Oguri Y , Olmstead RG , Onodera N , Petersen BL , Pils B , Prigge M , Rensing SA , Riano-Pachon DM , Roberts AW , Sato Y , Scheller HV , Schulz B , Schulz C , Shakirov EV , Shibagaki N , Shinohara N , Shippen DE , Sorensen I , Sotooka R , Sugimoto N , Sugita M , Sumikawa N , Tanurdzic M , Theissen G , Ulvskov P , Wakazuki S , Weng JK , Willats WW , Wipf D , Wolf PG , Yang L , Zimmer AD , Zhu Q , Mitros T , Hellsten U , Loque D , Otillar R , Salamov A , Schmutz J , Shapiro H , Lindquist E , Lucas S , Rokhsar D , Grigoriev IV
Ref : Science , 332 :960 , 2011
Abstract : Vascular plants appeared ~410 million years ago, then diverged into several lineages of which only two survive: the euphyllophytes (ferns and seed plants) and the lycophytes. We report here the genome sequence of the lycophyte Selaginella moellendorffii (Selaginella), the first nonseed vascular plant genome reported. By comparing gene content in evolutionarily diverse taxa, we found that the transition from a gametophyte- to a sporophyte-dominated life cycle required far fewer new genes than the transition from a nonseed vascular to a flowering plant, whereas secondary metabolic genes expanded extensively and in parallel in the lycophyte and angiosperm lineages. Selaginella differs in posttranscriptional gene regulation, including small RNA regulation of repetitive elements, an absence of the trans-acting small interfering RNA pathway, and extensive RNA editing of organellar genes.
ESTHER : Banks_2011_Science_332_960
PubMedSearch : Banks_2011_Science_332_960
PubMedID: 21551031
Gene_locus related to this paper: selml-d8qua5 , selml-d8qva1 , selml-d8qyh7 , selml-d8qza0 , selml-d8r5d4 , selml-d8r6d4 , selml-d8r504 , selml-d8r506 , selml-d8rbi1 , selml-d8rbs1 , selml-d8rck8 , selml-d8rf38 , selml-d8rkl6 , selml-d8rpr1 , selml-d8rpy0 , selml-d8ru47 , selml-d8ry54 , selml-d8rzp6 , selml-d8rzy7 , selml-d8s0c9 , selml-d8s0u3 , selml-d8s2t1 , selml-d8s3z8 , selml-d8s401 , selml-d8sba6 , selml-d8sch9 , selml-d8spq2 , selml-d8sq37 , selml-d8ssx7 , selml-d8swp2 , selml-d8t7a3 , selml-d8t8v4 , selml-d8taz4 , selml-d8tdq6 , selml-d8rai8 , selml-d8qt54 , selml-d8r2d8 , selml-d8rmd3 , selml-d8rra9 , selml-d8slg4 , selml-d8swp0 , selml-d8s7i0 , selml-d8qz37 , selml-d8sz00 , selml-d8s776 , selml-d8qw15 , selml-d8ska7 , selml-d8t0c4 , selml-d8r194 , selml-d8s5m8 , selml-d8s7r2 , selml-d8ta80 , selml-d8ru55

Title : The Ectocarpus genome and the independent evolution of multicellularity in brown algae - Cock_2010_Nature_465_617
Author(s) : Cock JM , Sterck L , Rouze P , Scornet D , Allen AE , Amoutzias G , Anthouard V , Artiguenave F , Aury JM , Badger JH , Beszteri B , Billiau K , Bonnet E , Bothwell JH , Bowler C , Boyen C , Brownlee C , Carrano CJ , Charrier B , Cho GY , Coelho SM , Collen J , Corre E , Da Silva C , Delage L , Delaroque N , Dittami SM , Doulbeau S , Elias M , Farnham G , Gachon CM , Gschloessl B , Heesch S , Jabbari K , Jubin C , Kawai H , Kimura K , Kloareg B , Kupper FC , Lang D , Le Bail A , LeBlanc C , Lerouge P , Lohr M , Lopez PJ , Martens C , Maumus F , Michel G , Miranda-Saavedra D , Morales J , Moreau H , Motomura T , Nagasato C , Napoli CA , Nelson DR , Nyvall-Collen P , Peters AF , Pommier C , Potin P , Poulain J , Quesneville H , Read B , Rensing SA , Ritter A , Rousvoal S , Samanta M , Samson G , Schroeder DC , Segurens B , Strittmatter M , Tonon T , Tregear JW , Valentin K , von Dassow P , Yamagishi T , Van de Peer Y , Wincker P
Ref : Nature , 465 :617 , 2010
Abstract : Brown algae (Phaeophyceae) are complex photosynthetic organisms with a very different evolutionary history to green plants, to which they are only distantly related. These seaweeds are the dominant species in rocky coastal ecosystems and they exhibit many interesting adaptations to these, often harsh, environments. Brown algae are also one of only a small number of eukaryotic lineages that have evolved complex multicellularity (Fig. 1). We report the 214 million base pair (Mbp) genome sequence of the filamentous seaweed Ectocarpus siliculosus (Dillwyn) Lyngbye, a model organism for brown algae, closely related to the kelps (Fig. 1). Genome features such as the presence of an extended set of light-harvesting and pigment biosynthesis genes and new metabolic processes such as halide metabolism help explain the ability of this organism to cope with the highly variable tidal environment. The evolution of multicellularity in this lineage is correlated with the presence of a rich array of signal transduction genes. Of particular interest is the presence of a family of receptor kinases, as the independent evolution of related molecules has been linked with the emergence of multicellularity in both the animal and green plant lineages. The Ectocarpus genome sequence represents an important step towards developing this organism as a model species, providing the possibility to combine genomic and genetic approaches to explore these and other aspects of brown algal biology further.
ESTHER : Cock_2010_Nature_465_617
PubMedSearch : Cock_2010_Nature_465_617
PubMedID: 20520714
Gene_locus related to this paper: ectsi-d7fm61 , ectsi-d7fs16 , ectsi-d7fsv3 , ectsi-d7fte8 , ectsi-d7fux6 , ectsi-d7fvr0 , ectsi-d7fvu4 , ectsi-d7fwk0 , ectsi-d7fyh7 , ectsi-d7g0w7 , ectsi-d7g6g5 , ectsi-d7g484 , ectsi-d7g686 , ectsi-d8lca9 , ectsi-d8lfv2 , ectsi-d8lqg6 , ectsi-d8ltj9 , ectsi-d7fjz2 , ectsi-d7g376

Title : Integrative analytical approach by capillary electrophoresis and kinetics under high pressure optimized for deciphering intrinsic and extrinsic cofactors that modulate activity and stability of human paraoxonase (PON1) - Renault_2010_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_878_1346
Author(s) : Renault F , Carus T , Clery-Barraud C , Elias M , Chabriere E , Masson P , Rochu D
Ref : Journal of Chromatography B Analyt Technol Biomed Life Sciences , 878 :1346 , 2010
Abstract : Paraoxonase (PON1) is working in vivo in a particular dynamic environment including HDL particles and associated molecules. To decipher the respective and/or concomitant role of the different cofactors involved in this molecular organization, an approach using multiple experimental techniques based on capillary electrophoresis and classical kinetics or kinetics under high pressure was implemented. The effects of calcium and phosphate as protein or plasma cofactor, of human phosphate binding protein (HPBP) as enzyme chaperone, and of a PON1 inhibitor as an active site stabilizer, on the catalytic activities and functional oligomerization of PON1 were scrutinized. PON1 displays two distinct catalytic behaviors, one against esters and lactones, the other against organophosphorus compounds; its functional states and catalytic activities against these substrates are differently modulated by the molecular environment; PON1 exists under several active multimeric forms; the binding of HPBP amends the size of the oligomeric states and exerts a stabilizing effect on the activities of PON1; PON1 functional properties are modulated by HPBP, calcium and phosphate. This integrative approach using several optimized analytical techniques allowed performing comparison of catalytic properties and oligomeric states of functional PON1 in different enzyme preparations. Relevance of these data to understand in vivo physiological PON1 functioning is mandatory.
ESTHER : Renault_2010_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_878_1346
PubMedSearch : Renault_2010_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_878_1346
PubMedID: 19945920

Title : Genomic analysis of the basal lineage fungus Rhizopus oryzae reveals a whole-genome duplication - Ma_2009_PLoS.Genet_5_e1000549
Author(s) : Ma LJ , Ibrahim AS , Skory C , Grabherr MG , Burger G , Butler M , Elias M , Idnurm A , Lang BF , Sone T , Abe A , Calvo SE , Corrochano LM , Engels R , Fu J , Hansberg W , Kim JM , Kodira CD , Koehrsen MJ , Liu B , Miranda-Saavedra D , O'Leary S , Ortiz-Castellanos L , Poulter R , Rodriguez-Romero J , Ruiz-Herrera J , Shen YQ , Zeng Q , Galagan J , Birren BW , Cuomo CA , Wickes BL
Ref : PLoS Genet , 5 :e1000549 , 2009
Abstract : Rhizopus oryzae is the primary cause of mucormycosis, an emerging, life-threatening infection characterized by rapid angioinvasive growth with an overall mortality rate that exceeds 50%. As a representative of the paraphyletic basal group of the fungal kingdom called "zygomycetes," R. oryzae is also used as a model to study fungal evolution. Here we report the genome sequence of R. oryzae strain 99-880, isolated from a fatal case of mucormycosis. The highly repetitive 45.3 Mb genome assembly contains abundant transposable elements (TEs), comprising approximately 20% of the genome. We predicted 13,895 protein-coding genes not overlapping TEs, many of which are paralogous gene pairs. The order and genomic arrangement of the duplicated gene pairs and their common phylogenetic origin provide evidence for an ancestral whole-genome duplication (WGD) event. The WGD resulted in the duplication of nearly all subunits of the protein complexes associated with respiratory electron transport chains, the V-ATPase, and the ubiquitin-proteasome systems. The WGD, together with recent gene duplications, resulted in the expansion of multiple gene families related to cell growth and signal transduction, as well as secreted aspartic protease and subtilase protein families, which are known fungal virulence factors. The duplication of the ergosterol biosynthetic pathway, especially the major azole target, lanosterol 14alpha-demethylase (ERG11), could contribute to the variable responses of R. oryzae to different azole drugs, including voriconazole and posaconazole. Expanded families of cell-wall synthesis enzymes, essential for fungal cell integrity but absent in mammalian hosts, reveal potential targets for novel and R. oryzae-specific diagnostic and therapeutic treatments.
ESTHER : Ma_2009_PLoS.Genet_5_e1000549
PubMedSearch : Ma_2009_PLoS.Genet_5_e1000549
PubMedID: 19578406

Title : Effects of date ( Phoenix dactylifera L., Medjool or Hallawi Variety) consumption by healthy subjects on serum glucose and lipid levels and on serum oxidative status: a pilot study - Rock_2009_J.Agric.Food.Chem_57_8010
Author(s) : Rock W , Rosenblat M , Borochov-Neori H , Volkova N , Judeinstein S , Elias M , Aviram M
Ref : Journal of Agricultural and Food Chemistry , 57 :8010 , 2009
Abstract : The present pilot study analyzed, for the first time, the in vivo effect of Medjool or Hallawi date consumption by healthy subjects on serum glucose, lipids, and oxidative stress. Total phenolics concentration in the Hallawi versus Medjool dates was greater by 20-31%. The major proportion of the soluble phenolics in both date varieties consisted of phenolic acids, mainly ferulic acid and coumaric acid derivatives, and also chlorogenic and caffeic acid derivatives. Unlike the Medjool dates, Hallawi dates contained a significant proportion of catechins as well. In addition, both varieties contained a quercetin derivative. Both date varieties possess antioxidative properties in vitro, but the ferric ion reducing antioxidant power of Hallawi versus Medjool dates was higher by 24%. Ten healthy subjects consumed, for a period of 4 weeks 100 g/day of either Medjool or Hallawi dates. The date consumption did not significantly affect the subjects' body mass index (BMI), their serum total cholesterol, or their cholesterol levels in the VLDL, LDL, or HDL fractions. Most important, fasting serum glucose and triacylglycerol levels were not increased after consumption of either date variety, and serum triacylglycerol levels even significantly (p < 0.05) decreased, by 8 or 15% after Medjool or Hallawi date consumption, respectively. Basal serum oxidative status was significantly (p < 0.01) decreased by 33%, as compared to the levels observed before consumption, after Hallawi (but not Medjool) date consumption. Similarly, the susceptibility of serum to AAPH-induced lipid peroxidation decreased by 12%, but only after Hallawi date consumption. In agreement with the above results, serum activity of the HDL-associated antioxidant enzyme paraoxonase 1 (PON1) significantly increased, by 8%, after Hallawi date consumption. It is concluded that date consumption (and mainly the Hallawi variety) by healthy subjects, despite their high sugar content, demonstrates beneficial effects on serum triacylglycerol and oxidative stress and does not worsen serum glucose and lipid/lipoprotein patterns, and thus can be considered an antiatherogenic nutrient .
ESTHER : Rock_2009_J.Agric.Food.Chem_57_8010
PubMedSearch : Rock_2009_J.Agric.Food.Chem_57_8010
PubMedID: 19681613

Title : Consumption of wonderful variety pomegranate juice and extract by diabetic patients increases paraoxonase 1 association with high-density lipoprotein and stimulates its catalytic activities - Rock_2008_J.Agric.Food.Chem_56_8704
Author(s) : Rock W , Rosenblat M , Miller-Lotan R , Levy AP , Elias M , Aviram M
Ref : Journal of Agricultural and Food Chemistry , 56 :8704 , 2008
Abstract : Association of paraoxonase 1 (PON1) with high-density lipoprotein (HDL) stabilizes the enzyme. In diabetic patients, PON1 dissociates from HDL and, as a consequence, is less biologically active. Our aim was to investigate the effects of Wonderful variety pomegranate juice (WPJ) and pomegranate polyphenol extract (WPOMxl) consumption on PON1 association with HDL in diabetic patients. Thirty patients with type 2 diabetes mellitus participated in the study. Ten male patients and 10 female patients received concentrated WPJ (50 mL/day for 4 weeks), while another group of 10 male patients received WPOMxl (5 mL/day for 6 weeks). There were no significant effects of WPJ or WPOMxl consumption on fasting blood glucose or hemoglobin A1c levels. After 4 weeks of WPJ consumption by male patients, basal serum oxidative stress was significantly decreased by 35%, whereas serum concentrations of thiol groups significantly increased by 25%. Moreover, HDL-associated PON1 arylesterase, paraoxonase, and lactonase activities increased significantly after WPJ consumption by 34-45%, as compared to the baseline levels. PON1 protein binding to HDL was significantly increased by 30% following WPJ consumption, and the enzyme became more stable. In male patients that consumed WPOMxl and in female patients that consumed PJ, a similar pattern was observed, although to a lesser extent. We conclude that WPJ as well as WPOMxl consumption by diabetic patients does not worsen their diabetic parameters. Furthermore, WPJ as well as WPOMxl consumption contribute to PON1 stabilization, increased association with HDL, and enhanced catalytic activities. These beneficial effects of pomegranate consumption on serum PON1 stability and activity could lead to retardation of atherosclerosis development in diabetic patients.
ESTHER : Rock_2008_J.Agric.Food.Chem_56_8704
PubMedSearch : Rock_2008_J.Agric.Food.Chem_56_8704
PubMedID: 18759451

Title : Structural basis for natural lactonase and promiscuous phosphotriesterase activities - Elias_2008_J.Mol.Biol_379_1017
Author(s) : Elias M , Dupuy J , Merone L , Mandrich L , Porzio E , Moniot S , Rochu D , Lecomte C , Rossi M , Masson P , Manco G , Chabriere E
Ref : Journal of Molecular Biology , 379 :1017 , 2008
Abstract : Organophosphates are the largest class of known insecticides, several of which are potent nerve agents. Consequently, organophosphate-degrading enzymes are of great scientific interest as bioscavengers and biodecontaminants. Recently, a hyperthermophilic phosphotriesterase (known as SsoPox), from the Archaeon Sulfolobus solfataricus, has been isolated and found to possess a very high lactonase activity. Here, we report the three-dimensional structures of SsoPox in the apo form (2.6 A resolution) and in complex with a quorum-sensing lactone mimic at 2.0 A resolution. The structure also reveals an unexpected active site topology, and a unique hydrophobic channel that perfectly accommodates the lactone substrate. Structural and mutagenesis evidence allows us to propose a mechanism for lactone hydrolysis and to refine the catalytic mechanism established for phosphotriesterases. In addition, SsoPox structures permit the correlation of experimental lactonase and phosphotriesterase activities and this strongly suggests lactonase activity as the cognate function of SsoPox. This example demonstrates that promiscuous activities probably constitute a large and efficient reservoir for the creation of novel catalytic activities.
ESTHER : Elias_2008_J.Mol.Biol_379_1017
PubMedSearch : Elias_2008_J.Mol.Biol_379_1017
PubMedID: 18486146

Title : Altered gene expression in Choristoneura fumiferana and Manduca sexta in response to sublethal intoxication by Bacillus thuringiensis Cry1Ab toxin - van Munster_2007_Insect.Mol.Biol_16_25
Author(s) : van Munster M , Prefontaine G , Meunier L , Elias M , Mazza A , Brousseau R , Masson L
Ref : Insect Molecular Biology , 16 :25 , 2007
Abstract : In order to understand how lepidopteran insects react physiologically to Bacillus thuringiensis crystal toxin ingestion, transcriptional profiling of Choristoneura fumiferana larvae exposed to sublethal doses of Cry1Ab protoxin were monitored using a C. fumiferana-specific cDNA microarray derived from a protoxin-specific subtractive library. Differential gene expression occurred primarily between 2 and 5 h postingestion. Metabolic enzymes such as lipases and proteases were generally repressed, whereas genes involved in detoxification, immune system regulation or general stress response were upregulated. A similar protoxin-specific transcriptional pattern was also observed with Manduca sexta larvae, using three upregulated genes (serpin, cytochrome P450 and carboxyl/cholinesterase) and one downregulated gene (beta-glucosidase), suggesting that a susceptible larval response to Cry toxin exposure might be universal among lepidopterous insects.
ESTHER : van Munster_2007_Insect.Mol.Biol_16_25
PubMedSearch : van Munster_2007_Insect.Mol.Biol_16_25
PubMedID: 17257206

Title : The Chlamydomonas genome reveals the evolution of key animal and plant functions - Merchant_2007_Science_318_245
Author(s) : Merchant SS , Prochnik SE , Vallon O , Harris EH , Karpowicz SJ , Witman GB , Terry A , Salamov A , Fritz-Laylin LK , Marechal-Drouard L , Marshall WF , Qu LH , Nelson DR , Sanderfoot AA , Spalding MH , Kapitonov VV , Ren Q , Ferris P , Lindquist E , Shapiro H , Lucas SM , Grimwood J , Schmutz J , Cardol P , Cerutti H , Chanfreau G , Chen CL , Cognat V , Croft MT , Dent R , Dutcher S , Fernandez E , Fukuzawa H , Gonzalez-Ballester D , Gonzalez-Halphen D , Hallmann A , Hanikenne M , Hippler M , Inwood W , Jabbari K , Kalanon M , Kuras R , Lefebvre PA , Lemaire SD , Lobanov AV , Lohr M , Manuell A , Meier I , Mets L , Mittag M , Mittelmeier T , Moroney JV , Moseley J , Napoli C , Nedelcu AM , Niyogi K , Novoselov SV , Paulsen IT , Pazour G , Purton S , Ral JP , Riano-Pachon DM , Riekhof W , Rymarquis L , Schroda M , Stern D , Umen J , Willows R , Wilson N , Zimmer SL , Allmer J , Balk J , Bisova K , Chen CJ , Elias M , Gendler K , Hauser C , Lamb MR , Ledford H , Long JC , Minagawa J , Page MD , Pan J , Pootakham W , Roje S , Rose A , Stahlberg E , Terauchi AM , Yang P , Ball S , Bowler C , Dieckmann CL , Gladyshev VN , Green P , Jorgensen R , Mayfield S , Mueller-Roeber B , Rajamani S , Sayre RT , Brokstein P , Dubchak I , Goodstein D , Hornick L , Huang YW , Jhaveri J , Luo Y , Martinez D , Ngau WC , Otillar B , Poliakov A , Porter A , Szajkowski L , Werner G , Zhou K , Grigoriev IV , Rokhsar DS , Grossman AR
Ref : Science , 318 :245 , 2007
Abstract : Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the approximately 120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella.
ESTHER : Merchant_2007_Science_318_245
PubMedSearch : Merchant_2007_Science_318_245
PubMedID: 17932292
Gene_locus related to this paper: chlre-a0a2k3e2k6 , chlre-a8hmd4 , chlre-a8hqa9 , chlre-a8htq0 , chlre-a8hus6.1 , chlre-a8hus6.2 , chlre-a8icg4 , chlre-a8iwm0 , chlre-a8ize5 , chlre-a8j2s9 , chlre-a8j5w6 , chlre-a8j7f8 , chlre-a8j8u9 , chlre-a8j8v0 , chlre-a8j9u6 , chlre-a8j143 , chlre-a8j248 , chlre-a8jd32 , chlre-a8jd42 , chlre-a8jgj2 , chlre-a8jhc8 , chlre-a8jhe5 , chlre-a8iwj1 , chlre-a8j7d5 , chlre-a0a2k3dii0

Title : Cloning, molecular characterization and expression of ecto-nucleoside triphosphate diphosphohydrolase-1 from Torpedo electric organ - Martin-Satue_2007_Neurochem.Int_50_256
Author(s) : Martin-Satue M , Torrejon-Escribano B , Felipe A , de Aranda IG , Elias M , Marsal J , Blasi J , Solsona C
Ref : Neurochem Int , 50 :256 , 2007
Abstract : During synaptic transmission large amounts of ATP are released from pre- and post-synaptic sources of Torpedo electric organ. A chain reaction sequentially hydrolyses ATP to adenosine, which inhibits acetylcholine secretion. The first enzyme implicated in this extracellular ATP hydrolysis is an ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) that dephosphorylates both ATP and ADP to AMP. This enzyme has been biochemically characterized in the synaptosomal fraction of Torpedo electric organ, having almost equal affinity for ATP as for ADP, a fact that pointed to the type-1 NTPDase enzyme. In the present work we describe the cloning and molecular characterization of the cDNA for an NTPDase from Torpedo marmorata electric organ. The clone, obtained using the RACE-PCR technique, contains and open-reading frame of 1506bp and encodes a 502 amino acids protein that exhibits high homology with other NTPDases1 from vertebrates previously identified, including those of zebrafish and Xenopus, as well as human, rat and mouse. Topology analyses revealed the existence of two transmembrane regions, two short cytoplasmic tails and a long extracellular domain containing five apyrase-conserved regions. Gene expression studies revealed that this gene is expressed in all the Torpedo tissues analyzed. Finally, activity and cellular localization of the protein encoded by this newly cloned cDNA was assessed by heterologous expression experiments involving COS-7 and HeLa cells.
ESTHER : Martin-Satue_2007_Neurochem.Int_50_256
PubMedSearch : Martin-Satue_2007_Neurochem.Int_50_256
PubMedID: 17030469

Title : Stabilization of the active form(s) of human paraoxonase by human phosphate-binding protein - Rochu_2007_Biochem.Soc.Trans_35_1616
Author(s) : Rochu D , Chabriere E , Renault F , Elias M , Clery-Barraud C , Masson P
Ref : Biochemical Society Transactions , 35 :1616 , 2007
Abstract : While there is a consensus that human PON1 (paraoxonase-1) has a protective role, its primary biological function remains unclear. A protective role against poisoning by organophosphates [OPs (organophosphorus compounds)] drove earlier works. Clinical interest has recently focused on a protective role of PON1 against vascular diseases. PON1 resides mainly on HDL (high-density lipoprotein) particles, and converging recent works show that both its activities and stability dramatically depend on this versatile and dynamic molecular environment. The discovery that HPBP (human phosphate-binding protein) has a firm tendency to associate with PON1 has steered new directions for characterizing PON1 functional state(s). Storage stability studies provided evidence that HPBP is involved in maintaining physiologically active PON1 conformation(s). Thermal stability studies showed that human PON1 is remarkably thermostable and that its association with HPBP strongly contributes to slowing down the denaturation rate. A hybrid PON1, displaying mutations that stabilized recombinant enzyme expressed in Escherichia coli, was shown to be more thermostable than natural human PON1. Predictably, its stability was unaffected by the presence of HPBP. Synergistic efforts on characterizing natural PON1 and rPON1 (recombinant PON1) provide information for the design of future stable mutants of PON1-based bioscavengers to be used as safe and effective countermeasures to challenge OPs. Maintaining a stable environment for such administrable human rPON1 should, at least, preserve the anti-atherogenic activity of the enzyme.
ESTHER : Rochu_2007_Biochem.Soc.Trans_35_1616
PubMedSearch : Rochu_2007_Biochem.Soc.Trans_35_1616
PubMedID: 18031277