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Author Thacker, C.; Rose, A.M. file  url
doi  openurl
  Title (up) A look at the Caenorhabditis elegans Kex2/Subtilisin-like proprotein convertase family Type Journal Article
  Year 2000 Publication BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology Abbreviated Journal Bioessays  
  Volume 22 Issue 6 Pages 545-553  
  Keywords Animals; Caenorhabditis elegans/*enzymology/genetics; Genes, Helminth; Humans; Multigene Family; Mutation; Phylogeny; *Proprotein Convertases; *Saccharomyces cerevisiae Proteins; Subtilisins/chemistry/genetics/*metabolism  
  Abstract Significant advances have recently been made in our understanding of the mechanisms of activation of proteins that require processing. Often this involves endoproteolytic cleavage of precursor forms at basic residues, and is carried out by a group of serine endoproteinases, termed the proprotein convertases. In mammals, seven different convertases have been identified to date. These act in both the regulated secretory pathway for the processing of prohormones and proneuropeptides and in the constitutive secretory pathway, in which a variety of proproteins are activated endoproteolytically. The recently completed sequence of the nematode Caenorhabditis elegans genome affords a unique opportunity to examine the entire proprotein convertase family in a multicellular organism. Here we review the nature of the family, emphasising the structural features, characteristic of the four nematode genes, that supply all of the necessary functions unique to this group of serine endoproteinases. Studies of the C. elegans genes not only provide important information about the evaluation of this gene family but should help to illuminate the roles of these proteins in mammalian systems. BioEssays 22:545-553, 2000.  
  Call Number Serial 522  
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Author Heinisch, J.J. file  url
doi  openurl
  Title (up) Baker's yeast as a tool for the development of antifungal kinase inhibitors--targeting protein kinase C and the cell integrity pathway Type Journal Article
  Year 2005 Publication Biochimica et Biophysica Acta Abbreviated Journal Biochim Biophys Acta  
  Volume 1754 Issue 1-2 Pages 171-182  
  Keywords Antifungal Agents/*chemistry/metabolism/pharmacology; Cell Cycle/*drug effects; Cell Wall/drug effects/metabolism; Enzyme Inhibitors/*chemistry/metabolism/pharmacology; Humans; MAP Kinase Signaling System/drug effects; Models, Biological; Protein Kinase C/*antagonists & inhibitors/chemistry/drug effects/metabolism; Protein Kinases/genetics/metabolism; Recombinant Fusion Proteins/chemistry/*metabolism; Saccharomyces cerevisiae/chemistry/enzymology/*metabolism; Saccharomyces cerevisiae Proteins/*antagonists & inhibitors/chemistry/drug effects/metabolism  
  Abstract Today, the yeast Saccharomyces cerevisiae is probably the best-studied eukaryotic organism. This review first focuses on the signaling process which is mediated by the unique yeast protein kinase C (Pkc1p) and a downstream mitogen-activated protein kinase (MAPK) cascade. This pathway ensures cellular integrity by sensing cell surface stress and controlling cell wall biosynthesis and progression through the cell cycle. The domain structure of Pkc1p is conserved from yeast to humans. A yeast system for heterologous expression of specific domains in a chimeric yeast/mammalian PKC enzyme (“domain shuffling”) is depicted. It is also proposed how this system could be employed for the study of protein kinase inhibitors in high-throughput screens. Moreover, a reporter assay that allows a quantitative readout of the activity of the cell integrity signaling pathway is introduced. Since a variety of protein kinases take part in the signal transduction, this broadens the range of targets for potential inhibitors.  
  Call Number Serial 554  
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Author Favelukes, G.; Stoppani, A.O. url  openurl
  Title (up) Baker's-yeast fumarase, a thiol enzyme Type Journal Article
  Year 1958 Publication Biochimica et Biophysica Acta Abbreviated Journal Biochim Biophys Acta  
  Volume 28 Issue 3 Pages 654-655  
  Keywords *Hydro-Lyases; Saccharomyces cerevisiae/*metabolism; *Hydrases; *SACCHAROMYCES CEREVISIAE/metabolism  
  Abstract  
  Call Number Grinnell @ engelk @ Serial 483  
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Author Mazzoni, C.; Falcone, C. file  url
openurl 
  Title (up) Caspase-dependent apoptosis in yeast Type Journal Article
  Year 2008 Publication Biochimica et Biophysica Acta Abbreviated Journal Biochim Biophys Acta  
  Volume 1783 Issue 7 Pages 1320-1327  
  Keywords Apoptosis--genetics, physiology; Apoptosis Regulatory Proteins--metabolism; Caspases--metabolism; Mitochondria--metabolism; Saccharomyces cerevisiae--genetics, physiology; Saccharomyces cerevisiae Proteins--metabolism; Signal Transduction  
  Abstract Damaging environment, certain intracellular defects or heterologous expression of pro-apoptotic genes induce death in yeast cells exhibiting typical markers of apoptosis. In mammals, apoptosis can be directed by the activation of groups of proteases, called caspases, that cleave specific substrates and trigger cell death. In addition, in plants, fungi, Dictyostelium and metazoa, paracaspases and metacaspases have been identified that share some homologies with caspases but showing different substrate specificity. In the yeast Saccharomyces cerevisiae, a gene (MCA1/YCA1) has been identified coding for a metacaspase involved in the induction of cell death. Metacaspases are not biochemical, but sequence and functional homologes of caspases, as deletion of them rescues entirely different death scenarios. In this review we will summarize the current knowledge in S. cerevisiae on apoptotic processes, induced by internal and external triggers, which are dependent on the metacaspase gene YCA1.  
  Call Number Serial 850  
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Author Weaver, T.; Lees, M.; Zaitsev, V.; Zaitseva, I.; Duke, E.; Lindley, P.; McSweeny, S.; Svensson, A.; Keruchenko, J.; Keruchenko, I.; Gladilin, K.; Banaszak, L. file  url
openurl 
  Title (up) Crystal structures of native and recombinant yeast fumarase Type Journal Article
  Year 1998 Publication Journal of Molecular Biology Abbreviated Journal J Mol Biol  
  Volume 280 Issue 3 Pages 431-442  
  Keywords Binding Sites; Crystallography, X-Ray; Fumarate Hydratase/*chemistry; Fungal Proteins/*chemistry; Models, Molecular; Polymers/chemistry; *Protein Conformation; Saccharomyces cerevisiae/*enzymology; Water/chemistry  
  Abstract Crystal structures for both native and recombinant forms of yeast fumarase from Saccharomyces cerevisiae have been completed to moderate resolution by two separate laboratories. The recombinant form was obtained by the construction of an expression plasmid for Escherichia coli. Despite a high level of amino acid sequence similarity, purification of the eukaryotic enzyme from the wild-type prokaryotic enzyme was feasible. The crystal structure of the native form, NY-fumarase, encompasses residues R22 through M484, while the recombinant form, RY-fumarase, consists of residues S27 through L485. Both crystal structures lack the N-terminal translocation segment. Each subunit of the homo-tetrameric protein has three domains. The active site is formed by segments from each of three polypeptide chains. The results of these studies on the eukaryotic proteins are unique, since the recombinant form was done in the absence of dicarboxylic acid and has an unoccupied active site. As a comparison, native fumarase was crystallized in the presence of the competitive inhibitor, meso-tartrate. Meso-tartrate occupies a position close to that of the bound citrate molecule found in the active site of the E. coli enzyme. This inhibitor participates in hydrogen bonding to an active-site water molecule. The independent determination of the two structures provides further evidence that an active-site water molecule may play an active role in the fumarase-catalyzed reaction.  
  Call Number Serial 1178  
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Author Durieu-Trautmann, O.; Delavier-Klutchko, C. file  url
openurl 
  Title (up) Effect of ammonia and glutamine on macromolecule synthesis and breakdown during sporulation of Saccharomyces cerevisiae Type Journal Article
  Year 1977 Publication Biochemical and Biophysical Research Communications Abbreviated Journal Biochem Biophys Res Commun  
  Volume 79 Issue 2 Pages 438-442  
  Keywords  
  Abstract The effect of two known inhibitors of sporulation in yeast, ammonia and glutamine, on certain biochemical events during sporogenesis have been studied using sporulating and non sporulating cells. Both strains gave similar results on the increase in dry cell weight, protein and RNA breakdown and the suppression of the intensive RNA and protein syntheses occurring after 4 hours. The inhibitory effect of ammonia and glutamine on RNA and protein syntheses is reversible under the same conditions which do so for sporulation.

Subject Headings: Ammonia/*pharmacology; DNA/biosynthesis; Fungal Proteins/biosynthesis; Glutamine/*pharmacology; Kinetics; RNA/biosynthesis; Saccharomyces cerevisiae/drug effects/*metabolism; Spores, Fungal/drug effects/metabolism
 
  Call Number Serial 2319  
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Author Yogev, O.; Yogev, O.; Singer, E.; Shaulian, E.; Goldberg, M.; Fox, T.D.; Pines, O. file  url
openurl 
  Title (up) Fumarase: a mitochondrial metabolic enzyme and a cytosolic/nuclear component of the DNA damage response Type Journal Article
  Year 2010 Publication PLoS Biology Abbreviated Journal PLoS Biol  
  Volume 8 Issue 3 Pages e1000328  
  Keywords Cell Nucleus/*metabolism; Cytosol/*metabolism; *DNA Damage; Fumarate Hydratase/genetics/*metabolism; Fumarates/metabolism; Gene Knockdown Techniques; HeLa Cells; Histones/genetics/metabolism; Humans; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism; Isoenzymes/genetics/*metabolism; Kidney Neoplasms/enzymology/genetics; Leiomyomatosis/enzymology/genetics; Mitochondria/*enzymology; Saccharomyces cerevisiae/enzymology/genetics; Saccharomyces cerevisiae Proteins/genetics/metabolism; Tumor Suppressor Proteins/genetics/metabolism  
  Abstract In eukaryotes, fumarase (FH in human) is a well-known tricarboxylic-acid-cycle enzyme in the mitochondrial matrix. However, conserved from yeast to humans is a cytosolic isoenzyme of fumarase whose function in this compartment remains obscure. A few years ago, FH was surprisingly shown to underlie a tumor susceptibility syndrome, Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). A biallelic inactivation of FH has been detected in almost all HLRCC tumors, and therefore FH was suggested to function as a tumor suppressor. Recently it was suggested that FH inhibition leads to elevated intracellular fumarate, which in turn acts as a competitive inhibitor of HPH (HIF prolyl hydroxylase), thereby causing stabilization of HIF (Hypoxia-inducible factor) by preventing proteasomal degradation. The transcription factor HIF increases the expression of angiogenesis regulated genes, such as VEGF, which can lead to high microvessel density and tumorigenesis. Yet this mechanism does not fully explain the large cytosolic population of fumarase molecules. We constructed a yeast strain in which fumarase is localized exclusively to mitochondria. This led to the discovery that the yeast cytosolic fumarase plays a key role in the protection of cells from DNA damage, particularly from DNA double-strand breaks. We show that the cytosolic fumarase is a member of the DNA damage response that is recruited from the cytosol to the nucleus upon DNA damage induction. This function of fumarase depends on its enzymatic activity, and its absence in cells can be complemented by high concentrations of fumaric acid. Our findings suggest that fumarase and fumaric acid are critical elements of the DNA damage response, which underlies the tumor suppressor role of fumarase in human cells and which is most probably HIF independent. This study shows an exciting crosstalk between primary metabolism and the DNA damage response, thereby providing a scenario for metabolic control of tumor propagation.  
  Call Number Serial 1880  
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Author Van de Ven, W.J.; Creemers, J.W.; Roebroek, A.J. file  url
openurl 
  Title (up) Furin: the prototype mammalian subtilisin-like proprotein-processing enzyme. Endoproteolytic cleavage at paired basic residues of proproteins of the eukaryotic secretory pathway Type Journal Article
  Year 1991 Publication Enzyme Abbreviated Journal Enzyme  
  Volume 45 Issue 5-6 Pages 257-270  
  Keywords Animals; Binding Sites; Catalysis; Cloning, Molecular; Drosophila melanogaster; Furin; Humans; Invertebrate Hormones/genetics/metabolism; Mice; Models, Molecular; Multigene Family; Protein Conformation; Protein Precursors/*metabolism; *Protein Processing, Post-Translational; Sequence Homology, Amino Acid; Substrate Specificity; Subtilisins/genetics/*metabolism  
  Abstract Furin, the translational product of the recently discovered fur gene, appears to be the first known mammalian member of the subtilisin family of serine proteases and the first known mammalian proprotein-processing enzyme with cleavage selectivity for paired basic amino acid residues. Structurally and functionally, it resembles the prohormone-processing enzyme, kexin (EC 3.4.21.61), which is encoded by the KEX2 gene of yeast Saccharomyces cerevisiae. Most likely, furin is primarily involved in the processing of precursors of proteins that are secreted via the constitutive secretory pathway. Here, we review the discovery of the fur gene and describe the isolation of cDNA clones corresponding to human and mouse fur and to two fur-like genes of Drosophila melanogaster, Dfur1 and Dfur2. We also compare the structural organization of the various deduced furin proteins to that of yeast kexin, and of other members of the subtilisin family of serine proteases. Furthermore, the biosynthesis of biologically active human and mouse furin is evaluated. Finally, the cleavage specificity for paired basic amino acid residues of human and mouse furin is demonstrated by the correct processing of the precursor for von Willebrand factor.  
  Call Number Serial 524  
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Author Williams, R.P.; Gott, C.L.; Qadri, S.M.; Scott, R.H. file  url
openurl 
  Title (up) Influence of temperature of incubation and type of growth medium on pigmentation in Serratia marcescens Type Journal Article
  Year 1971 Publication Journal of Bacteriology Abbreviated Journal J Bacteriol  
  Volume 106 Issue 2 Pages 438-443  
  Keywords Anti-Bacterial Agents/*biosynthesis; Bacterial Proteins/biosynthesis; Bacteriological Techniques; Caseins; Cell Division; Chloramphenicol/pharmacology; *Culture Media; Hot Temperature; Hydrogen-Ion Concentration; Oxygen; Pigments, Biological/*biosynthesis; Prodigiosin/biosynthesis; Protein Hydrolysates; Pyrroles/*biosynthesis; Saccharomyces; Serratia marcescens/cytology/drug effects/growth & development/*metabolism; Spectrophotometry; *Temperature; Time Factors  
  Abstract Maximal amounts of prodigiosin were synthesized in either minimal or complete medium after incubation of cultures at 27 C for 7 days. Biosynthesis of prodigiosin began earlier and the range of temperature for formation was greater in complete medium. No prodigiosin was formed in either medium when cultures were incubated at 38 C; however, after a shift to 27 C, pigmentation ensued, provided the period of incubation at 38 C was not longer than 36 hr for minimal medium or 48 hr for complete medium. Washed, nonpigmented cells grown in either medium at 38 C for 72 hr could synthesize prodigiosin when suspended in saline at 27 C when casein hydrolysate was added. These suspensions produced less prodigiosin at a slower rate than did cultures growing in casein hydrolysate at 27 C without prior incubation at 38 C. Optimal concentration of casein hydrolysate for pigment formation by suspensions was 0.4%; optimal temperature was 27 C. Anaerobic incubation, shift back to 38 C, killing cells by heating, or chloramphenicol (25 mug/ml) inhibited pigmentation. Suspensions of washed cells forming pigment reached pH 8.0 to 8.3 rapidly and maintained this pH throughout incubation for 7 days. Measurements of viable count and of protein, plus other data, indicated that cellular multiplication did not occur in suspensions of washed cells during pigment formation. By this procedure utilizing a shift down in temperature, biosynthesis of prodigiosin by washed cells could be separated from multiplication of bacteria.  
  Call Number Serial 1615  
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Author Parsons, A.B.; Brost, R.L.; Ding, H.; Li, Z.; Zhang, C.; Sheikh, B.; Brown, G.W.; Kane, P.M.; Hughes, T.R.; Boone, C. file  url
doi  openurl
  Title (up) Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathways Type Journal Article
  Year 2004 Publication Nature Biotechnology Abbreviated Journal Nat Biotechnol  
  Volume 22 Issue 1 Pages 62-69  
  Keywords Biotechnology/*methods; Cluster Analysis; Drug Industry/*methods; *Drug Resistance; Fungal Proteins/metabolism; Gene Deletion; *Gene Expression Regulation; Mutation; Pharmacogenetics; Proton-Translocating ATPases/metabolism; Saccharomyces cerevisiae/*genetics; Software  
  Abstract Bioactive compounds can be valuable research tools and drug leads, but it is often difficult to identify their mechanism of action or cellular target. Here we investigate the potential for integration of chemical-genetic and genetic interaction data to reveal information about the pathways and targets of inhibitory compounds. Taking advantage of the existing complete set of yeast haploid deletion mutants, we generated drug-hypersensitivity (chemical-genetic) profiles for 12 compounds. In addition to a set of compound-specific interactions, the chemical-genetic profiles identified a large group of genes required for multidrug resistance. In particular, yeast mutants lacking a functional vacuolar H(+)-ATPase show multidrug sensitivity, a phenomenon that may be conserved in mammalian cells. By filtering chemical-genetic profiles for the multidrug-resistant genes and then clustering the compound-specific profiles with a compendium of large-scale genetic interaction profiles, we were able to identify target pathways or proteins. This method thus provides a powerful means for inferring mechanism of action.  
  Call Number Serial 339  
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