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ABSTRACT: The inhibition of human dipeptidyl peptidase IV/CD26 (hDPPIV) is an accepted treatment for type 2 diabetes. In this study, an extracellular production system of hDPPIV using Saccharomyces cerevisiae was established to facilitate the screening of hDPPIV inhibitors. As dipeptides that mimic the hDPPIV substrate are candidate inhibitors of this protein, X-Ala or X-Pro dipeptides (in which X represents any amino acid) were tested systematically. Based on the results obtained in the first screening, a second screening was performed for Trp-X dipeptides. To elucidate the manner via which the physicochemical features at the P(1) and P(2) positions contributed to the hDPPIV inhibitory effect, correlations between the inhibitory activity of dipeptides and 13 amino acid indices were analyzed. The most effective inhibitory dipeptide was Trp-Pro (Ki = 0.04 mM). The mode of inhibition of hDPPIV by dipeptides was explained well by some amino acid indices and by the structure of the substrate-binding site of hDPPIV. The information obtained from the systematic analysis of a dipeptide library provides important clues for the development of hDPPIV targeting drugs and functional foods for type 2 diabetes.
Biochemical and Biophysical Research Communications 12/2012; · 2.48 Impact Factor
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Keisuke Ito,
Arkaitz Carracedo,
Dror Weiss,
Fumio Arai,
Ugo Ala,
David E Avigan,
Zachary T Schafer,
Ronald M Evans,
Toshio Suda,
Chih-Hao Lee,
Pier Paolo Pandolfi
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ABSTRACT: Stem-cell function is an exquisitely regulated process. Thus far, the contribution of metabolic cues to stem-cell function has not been well understood. Here we identify a previously unknown promyelocytic leukemia (PML)-peroxisome proliferator-activated receptor δ (PPAR-δ)-fatty-acid oxidation (FAO) pathway for the maintenance of hematopoietic stem cells (HSCs). We have found that loss of PPAR-δ or inhibition of mitochondrial FAO induces loss of HSC maintenance, whereas treatment with PPAR-δ agonists improved HSC maintenance. PML exerts its essential role in HSC maintenance through regulation of PPAR signaling and FAO. Mechanistically, the PML-PPAR-δ-FAO pathway controls the asymmetric division of HSCs. Deletion of Ppard or Pml as well as inhibition of FAO results in the symmetric commitment of HSC daughter cells, whereas PPAR-δ activation increased asymmetric cell division. Thus, our findings identify a metabolic switch for the control of HSC cell fate with potential therapeutic implications.
Nature medicine 08/2012; · 27.14 Impact Factor
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Isabel Garcia-Cao,
Min Sup Song,
Robin M Hobbs,
Gaelle Laurent,
Carlotta Giorgi,
Vincent C J de Boer,
Dimitrios Anastasiou, Keisuke Ito,
Atsuo T Sasaki,
Lucia Rameh,
Arkaitz Carracedo,
Matthew G Vander Heiden,
Lewis C Cantley,
Paolo Pinton,
Marcia C Haigis,
Pier Paolo Pandolfi
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ABSTRACT: Decremental loss of PTEN results in cancer susceptibility and tumor progression. PTEN elevation might therefore be an attractive option for cancer prevention and therapy. We have generated several transgenic mouse lines with PTEN expression elevated to varying levels by taking advantage of bacterial artificial chromosome (BAC)-mediated transgenesis. The "Super-PTEN" mutants are viable and show reduced body size due to decreased cell number, with no effect on cell size. Unexpectedly, PTEN elevation at the organism level results in healthy metabolism characterized by increased energy expenditure and reduced body fat accumulation. Cells derived from these mice show reduced glucose and glutamine uptake and increased mitochondrial oxidative phosphorylation and are resistant to oncogenic transformation. Mechanistically we find that PTEN elevation orchestrates this metabolic switch by regulating PI3K-dependent and -independent pathways and negatively impacting two of the most pronounced metabolic features of tumor cells: glutaminolysis and the Warburg effect.
Cell 03/2012; 149(1):49-62. · 32.40 Impact Factor
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ABSTRACT: In this study, the production of eight G protein-coupled receptors by Saccharomyces cerevisiae was compared using two types of media, one of which contained soy peptides and the other free amino acids. Yeast cell growth improved in the medium with soy peptides, and the expression levels of six of the receptors increased during the exponential phase by an average of 2.3-fold as against the free amino acid-based medium. The enhancement of protein expression by soy peptides can be explained by alleviation of metabolite stress due to amino acid source depletion caused by heterologous protein expression.
Bioscience Biotechnology and Biochemistry 01/2012; 76(3):628-31. · 1.28 Impact Factor
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ABSTRACT: Yeast's extracellular expression provides a cost-efficient means of producing industrially useful recombinant proteins. However, depending on the protein to be expressed, the production results in a poor yield, which is occasionally accompanied with loss of the expression plasmid and hence hampered growth of the host in the inducing medium. Here we propose an alternative approach, high cell-density expression, to improve the yield of a certain range of so-called difficult-to-express proteins. In this expression system, recombinant yeast cells resting in stationary phase (OD(660)=3-4) are suspended in a small aliquot of inducing medium to form a high cell-density culture (e.g., OD(660)=15). When applied to the yeast strains harboring Lentinula edodes laccase (Lcc1 or Lcc4) expressing plasmids, the high cell-density system allowed the host cells to synthesize elevated amounts of the laccase which resulted in >1000- to 6000-fold higher yield than those synthesized in a classical growth-associated manner. The resting cells required aerobic agitation for the maximum production. The production system also worked for other foreign enzymes but not for beta-galactosidase from Aspergillus oryzae or Escherichia coli, likely suggesting an involvement of chaperons that act on a certain range of secretory proteins.
Journal of Bioscience and Bioengineering 11/2011; 113(2):154-9. · 1.79 Impact Factor
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ABSTRACT: Miraculin (MCL) is a homodimeric protein isolated from the red berries of Richadella dulcifica. MCL, although flat in taste at neutral pH, has taste-modifying activity to convert sour stimuli to sweetness. Once MCL is held on the tongue, strong sweetness is sensed over 1 h each time we taste a sour solution. Nevertheless, no molecular mechanism underlying the taste-modifying activity has been clarified. In this study, we succeeded in quantitatively evaluating the acid-induced sweetness of MCL using a cell-based assay system and found that MCL activated hT1R2-hT1R3 pH-dependently as the pH decreased from 6.5 to 4.8, and that the receptor activation occurred every time an acid solution was applied. Although MCL per se is sensory-inactive at pH 6.7 or higher, it suppressed the response of hT1R2-hT1R3 to other sweeteners at neutral pH and enhanced the response at weakly acidic pH. Using human/mouse chimeric receptors and molecular modeling, we revealed that the amino-terminal domain of hT1R2 is required for the response to MCL. Our data suggest that MCL binds hT1R2-hT1R3 as an antagonist at neutral pH and functionally changes into an agonist at acidic pH, and we conclude this may cause its taste-modifying activity.
Proceedings of the National Academy of Sciences 09/2011; 108(40):16819-24. · 9.68 Impact Factor
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ABSTRACT: Neoculin, a sweet protein found in the fruit of Curculigo latifolia, has the ability to change sourness into sweetness. Neoculin turns drinking water sweet, indicating that non-acidic compounds may induce the sweetness. We report that ammonium chloride and certain amino acids elicit the intense sweetness of neoculin. Neoculin can thus sweeten amino acid-enriched foods.
Bioscience Biotechnology and Biochemistry 08/2011; 75(8):1600-2. · 1.28 Impact Factor
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ABSTRACT: We have developed a device that analyses the interaction of food components with model epithelial cells using surface plasmon resonance (SPR). A model of epithelial lingual cells was devised using a liposome composed of a mixture of four phospholipids. The liposome was immobilised to the L1 sensor tip attached to the sensor port of the SPR system. The interaction of food components with the model lingual epithelial cells was determined by the patterns of sensorgrams. According to this method, food components were classified into three groups: group A, strong interaction with the lipid bilayer; group B, weak interaction; and group C, neither A- nor B-type interaction. The sensorgrams of group A showed gradual binding and slow dissociation from the surface of the lipid bilayer. In group B, the food components showed rapid binding and rapid dissociation from the lipid bilayer. The compounds in group C exhibited weak binding to the lipid bilayer, but parts of these samples formed rigid complexes with the lipid bilayer. Sweet proteins producing prolonged sweetness perception as well as miraculin with its taste-modifying activity were classified into group A. The sensory activities of these substances are probably induced by their strong interactions with the epithelial cell surface; they have distinct binding constants with the lipid bilayer. Thaumatin exhibited the strongest interaction, followed by monellin and miraculin. Copyright © 2011 John Wiley & Sons, Ltd.
Flavour and Fragrance Journal 06/2011; 26(4):274 - 278. · 1.42 Impact Factor
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Natsuko Tokuda,
Kiyohiko Igarashi,
Tatsuro Shimamura,
Takami Yurugi-Kobayashi,
Mitsunori Shiroishi, Keisuke Ito,
Taishi Sugawara,
Hidetsugu Asada,
Takeshi Murata,
Norimichi Nomura,
So Iwata,
Takuya Kobayashi
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ABSTRACT: Anion exchangers are membrane proteins that have been identified in a wide variety of species, where they transport Cl(-) and HCO3(-)across the cell membrane. In this study, we cloned an anion-exchange protein from the genome of the basidiomycete Phanerochaete chrysosporium (PcAEP). PcAEP is a 618-amino acid protein that is homologous to the human anion exchanger (AE1) with 22.9% identity and 40.3% similarity. PcAEP was overexpressed by introducing the PcAEP gene into the genome of Pichia pastoris. As a result, PcAEP localized in the membrane of P. pastoris and was solubilized successfully by n-dodecyl-β-D-maltoside. His-tagged PcAEP was purified as a single band on SDS-PAGE using immobilized metal affinity chromatography and gel filtration chromatography. Purified PcAEP was found to bind to SITS, an inhibitor of the AE family, suggesting that the purified protein is folded properly. PcAEP expressed and purified using the present system could be useful for biological and structural studies of the anion exchange family of proteins.
Protein Expression and Purification 04/2011; 79(1):81-7. · 1.59 Impact Factor
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ABSTRACT: Glucansucrase (GSase) from Streptococcus mutans is an essential agent in dental caries pathogenesis. Here, we report the crystal structure of S. mutans glycosyltransferase (GTF-SI), which synthesizes soluble and insoluble glucans and is a glycoside hydrolase (GH) family 70 GSase in the free enzyme form and in complex with acarbose and maltose. Resolution of the GTF-SI structure confirmed that the domain order of GTF-SI is circularly permuted as compared to that of GH family 13 α-amylases. As a result, domains A, B and IV of GTF-SI are each composed of two separate polypeptide chains. Structural comparison of GTF-SI and amylosucrase, which is closely related to GH family 13 amylases, indicated that the two enzymes share a similar transglycosylation mechanism via a glycosyl-enzyme intermediate in subsite -1. On the other hand, novel structural features were revealed in subsites +1 and +2 of GTF-SI. Trp517 provided the platform for glycosyl acceptor binding, while Tyr430, Asn481 and Ser589, which are conserved in family 70 enzymes but not in family 13 enzymes, comprised subsite +1. Based on the structure of GTF-SI and amino acid comparison of GTF-SI, GTF-I and GTF-S, Asp593 in GTF-SI appeared to be the most critical point for acceptor sugar orientation, influencing the transglycosylation specificity of GSases, that is, whether they produced insoluble glucan with α(1-3) glycosidic linkages or soluble glucan with α(1-6) linkages. The structural information derived from the current study should be extremely useful in the design of novel inhibitors that prevent the biofilm formation by GTF-SI.
Journal of Molecular Biology 02/2011; 408(2):177-86. · 4.00 Impact Factor
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Ken-ichiro Nakajima,
Kanako Yokoyama,
Taichi Koizumi,
Ayako Koizumi,
Tomiko Asakura,
Tohru Terada,
Katsuyoshi Masuda, Keisuke Ito,
Akiko Shimizu-Ibuka,
Takumi Misaka,
Keiko Abe
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ABSTRACT: Neoculin occurring in the tropical fruit of Curculigo latifolia is currently the only protein that possesses both a sweet taste and a taste-modifying activity of converting sourness into sweetness. Structurally, this protein is a heterodimer consisting of a neoculin acidic subunit (NAS) and a neoculin basic subunit (NBS). Recently, we found that a neoculin variant in which all five histidine residues are replaced with alanine elicits intense sweetness at both neutral and acidic pH but has no taste-modifying activity. To identify the critical histidine residue(s) responsible for this activity, we produced a series of His-to-Ala neoculin variants and evaluated their sweetness levels using cell-based calcium imaging and a human sensory test. Our results suggest that NBS His11 functions as a primary pH sensor for neoculin to elicit taste modification. Neoculin variants with substitutions other than His-to-Ala were further analyzed to clarify the role of the NBS position 11 in the taste-modifying activity. We found that the aromatic character of the amino acid side chain is necessary to elicit the pH-dependent sweetness. Interestingly, since the His-to-Tyr variant is a novel taste-modifying protein with alternative pH sensitivity, the position 11 in NBS can be critical to modulate the pH-dependent activity of neoculin. These findings are important for understanding the pH-sensitive functional changes in proteinaceous ligands in general and the interaction of taste receptor-taste substance in particular.
PLoS ONE 01/2011; 6(4):e19448. · 4.09 Impact Factor
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Hidetsugu Asada,
Tomoko Uemura,
Takami Yurugi-Kobayashi,
Mitsunori Shiroishi,
Tatsuro Shimamura,
Hirokazu Tsujimoto, Keisuke Ito,
Taishi Sugawara,
Takanori Nakane,
Norimichi Nomura,
Takeshi Murata,
Tatsuya Haga,
So Iwata,
Takuya Kobayashi
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ABSTRACT: Various protein expression systems, such as Escherichia coli (E. coli), Saccharomyces cerevisiae (S. cerevisiae), Pichia pastoris (P. pastoris), insect cells and mammalian cell lines, have been developed for the synthesis of G protein-coupled receptors (GPCRs) for structural studies. Recently, the crystal structures of four recombinant human GPCRs, namely β2 adrenergic receptor, adenosine A2a receptor, CXCR4 and dopamine D3 receptor, were successfully determined using an insect cell expression system. GPCRs expressed in insect cells are believed to undergo mammalian-like posttranscriptional modifications and have similar functional properties than in mammals. Crystal structures of GPCRs have not yet been solved using yeast expression systems. In the present study, P. pastoris and insect cell expression systems for the human muscarinic acetylcholine receptor M2 subtype (CHRM2) were developed and the quantity and quality of CHRM2 synthesized by both expression systems were compared for the application in structural studies.
The ideal conditions for the expression of CHRM2 in P. pastoris were 60 hr at 20°C in a buffer of pH 7.0. The specific activity of the expressed CHRM2 was 28.9 pmol/mg of membrane protein as determined by binding assays using [3H]-quinuclidinyl benzilate (QNB). Although the specific activity of the protein produced by P. pastoris was lower than that of Sf9 insect cells, CHRM2 yield in P. pastoris was 2-fold higher than in Sf9 insect cells because P. pastoris was cultured at high cell density. The dissociation constant (Kd) for QNB in P. pastoris was 101.14 ± 15.07 pM, which was similar to that in Sf9 insect cells (86.23 ± 8.57 pM). There were no differences in the binding affinity of CHRM2 for QNB between P. pastoris and Sf9 insect cells.
Compared to insect cells, P. pastoris is easier to handle, can be grown at lower cost, and can be expressed quicker at a large scale. Yeast, P. pastoris, and insect cells are all effective expression systems for GPCRs. The results of the present study strongly suggested that protein expression in P. pastoris can be applied to the structural and biochemical studies of GPCRs.
Microbial Cell Factories 01/2011; 10:24. · 3.55 Impact Factor
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ABSTRACT: A new device for evaluating the continuity of taste was developed with the use of surface plasmon resonance (SPR). The model of lingual cells was constructed with liposomes immobilized onto an L1 sensor chip for SPR. Using this device, we classified food components into three categories according to the sensorgram pattern and residual ratio on lipid bilayer. Samples in group A strongly interacted with lipid bilayer, those in group B poorly interacted, and those in group C belong to neither group A nor group B. Sweet proteins and gymnemic acids that prolonged sweet perception were categorized in group A. Almost all the carbohydrates investigated and aspartame, of which the taste perception does not continue, belonged to group B. This device made it possible to detect the interaction with lipid bilayer and dissected the mechanism of taste continuity.
Journal of Agricultural and Food Chemistry 11/2010; 58(22):11870-5. · 2.82 Impact Factor
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Keisuke Ito,
Taishi Sugawara,
Ayako Koizumi,
Ken-ichiro Nakajima,
Akiko Shimizu-Ibuka,
Mitsunori Shiroishi,
Hidetsugu Asada,
Takami Yurugi-Kobayashi,
Tatsuro Shimamura,
Tomiko Asakura,
Takumi Misaka,
So Iwata,
Takuya Kobayashi,
Keiko Abe
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ABSTRACT: PURPOSE OF WORK: Soluble protein expression is an important first step during various types of protein studies. Here, we present the screening strategy of secretable mutant. The strategy aimed to identify those cysteine residues that provoke protein misfolding in the heterologous expression system. Intentional mutagenesis studies should consider the size of the library and the time required for expression screening. Here, we proposed a cysteine-to-serine shuffling mutation strategy (CS shuffling) using a Saccharomyces cerevisiae expression system. This strategy of site-directed shuffling mutagenesis of cysteine-to-serine residues aims to identify the cysteine residues that cause protein misfolding in heterologous expression. In the case of a nonglycosylated mutant of the taste-modifying protein miraculin (MCL), which was used here as a model protein, 25% of all constructs obtained from CS shuffling expressed MCL mutant, and serine mutations were found at Cys47 or Cys92, which are involved in the formation of the disulfide bond. This indicates that these residues had the potential to provoke protein misfolding via incorrect disulfide bonding. The CS shuffling can be performed using a small library and within one week, and is an effective screening strategy of soluble protein expression.
Biotechnology Letters 10/2010; 33(1):103-7. · 1.68 Impact Factor
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Carlotta Giorgi, Keisuke Ito,
Hui-Kuan Lin,
Clara Santangelo,
Mariusz R Wieckowski,
Magdalena Lebiedzinska,
Angela Bononi,
Massimo Bonora,
Jerzy Duszynski,
Rosa Bernardi,
Rosario Rizzuto,
Carlo Tacchetti,
Paolo Pinton,
Pier Paolo Pandolfi
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ABSTRACT: The promyelocytic leukemia (PML) tumor suppressor is a pleiotropic modulator of apoptosis. However, the molecular basis for such a diverse proapoptotic role is currently unknown. We show that extranuclear Pml was specifically enriched at the endoplasmic reticulum (ER) and at the mitochondria-associated membranes, signaling domains involved in ER-to-mitochondria calcium ion (Ca(2+)) transport and in induction of apoptosis. We found Pml in complexes of large molecular size with the inositol 1,4,5-trisphosphate receptor (IP(3)R), protein kinase Akt, and protein phosphatase 2a (PP2a). Pml was essential for Akt- and PP2a-dependent modulation of IP(3)R phosphorylation and in turn for IP(3)R-mediated Ca(2+) release from ER. Our findings provide a mechanistic explanation for the pleiotropic role of Pml in apoptosis and identify a pharmacological target for the modulation of Ca(2+) signals.
Science 10/2010; 330(6008):1247-51. · 31.20 Impact Factor
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Takanobu Sakurai,
Takumi Misaka,
Masaji Ishiguro,
Katsuyoshi Masuda,
Taishi Sugawara, Keisuke Ito,
Takuya Kobayashi,
Shinji Matsuo,
Yoshiro Ishimaru,
Tomiko Asakura,
Keiko Abe
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ABSTRACT: G-protein-coupled receptors mediate the senses of taste, smell, and vision in mammals. Humans recognize thousands of compounds as bitter, and this response is mediated by the hTAS2R family, which is one of the G-protein-coupled receptors composed of only 25 receptors. However, structural information on these receptors is limited. To address the molecular basis of bitter tastant discrimination by the hTAS2Rs, we performed ligand docking simulation and functional analysis using a series of point mutants of hTAS2R16 to identify its binding sites. The docking simulation predicted two candidate binding structures for a salicin-hTAS2R16 complex, and at least seven amino acid residues in transmembrane 3 (TM3), TM5, and TM6 were shown to be involved in ligand recognition. We also identified the probable salicin-hTAS2R16 binding mode using a mutated receptor experiment. This study characterizes the molecular interaction between hTAS2R16 and beta-D-glucopyranoside and will also facilitate rational design of bitter blockers.
Journal of Biological Chemistry 09/2010; 285(36):28373-8. · 4.77 Impact Factor
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Keisuke Ito,
Taishi Sugawara,
Ayako Koizumi,
Ken-Ichiro Nakajima,
Akiko Shimizu-Ibuka,
Mitsunori Shiroishi,
Hidetsugu Asada,
Takami Yurugi-Kobayashi,
Tatsuro Shimamura,
Tomiko Asakura,
Katsuyoshi Masuda,
Masaji Ishiguro,
Takumi Misaka,
So Iwata,
Takuya Kobayashi,
Keiko Abe
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ABSTRACT: Miraculin (MCL) is a taste-modifying protein that converts sourness into sweetness. The molecular mechanism underlying the taste-modifying action of MCL is unknown.
Here, a yeast expression system for MCL was constructed to accelerate analysis of its structure-function relationships. The Saccharomyces cerevisiae expression system has advantages as a high-throughput analysis system, but compared to other hosts it is characterized by a relatively low level of recombinant protein expression. To alleviate this weakness, in this study we optimized the codon usage and signal-sequence as the first step. Recombinant MCL (rMCL) was expressed and purified, and the sensory taste was analyzed.
As a result, a 2 mg/l yield of rMCL was successfully obtained. Although sensory taste evaluation showed that rMCL was flat in taste under all the pH conditions employed, taste-modifying activity similar to that of native MCL was recovered after deglycosylation. Mutagenetic analysis revealed that the N-glycan attached to Asn42 was bulky in rMCL.
The high-mannose-type N-glycan attached in yeast blocks the taste-modifying activity of rMCL.
The bulky N-glycan attached to Asn42 may cause steric hindrance in the interaction between active residues and the sweet taste receptor hT1R2/hT1R3.
Biochimica et Biophysica Acta 09/2010; 1800(9):986-92. · 4.66 Impact Factor
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ABSTRACT: Glucansucrases encoded by Streptococcus mutans play essential roles in the synthesis of sticky dental plaques. Based on amino-acid sequence similarity, glucansucrases are classified as members of glycoside hydrolase family 70 (GH 70). Data on the crystal structure of GH 70 glucansucrases have yet to be reported. Here, the GH 70 glucansucrase GTF-SI from S. mutans was overexpressed in Escherichia coli strain BL21 (DE3), purified to homogeneity and crystallized using the hanging-drop vapour-diffusion method. Orthorhombic GTF-SI crystals belonging to space group P2(1)2(1)2 were obtained. A diffraction data set was collected to 2.1 A resolution.
Acta Crystallographica Section F Structural Biology and Crystallization Communications 09/2010; 66(Pt 9):1086-8. · 0.51 Impact Factor
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ABSTRACT: Neoculin has pH-dependent taste-modifying activity. This study found that neoculin changed pH-dependently in its tryptophan- and ANS-derived fluorescence spectra, while no such change occurred in a neoculin variant whose histidine residues were replaced with alanine. These results suggest that the sweetness of neoculin depends on structural change accompanying the pH change, with the histidine residues playing a key role.
Bioscience Biotechnology and Biochemistry 11/2009; 73(11):2552-5. · 1.28 Impact Factor
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Takahiro Maeda, Keisuke Ito,
Taha Merghoub,
Laura Poliseno,
Robin M Hobbs,
Guocan Wang,
Lin Dong,
Manami Maeda,
Louis C Dore,
Arthur Zelent,
Lucio Luzzatto,
Julie Teruya-Feldstein,
Mitchell J Weiss,
Pier Paolo Pandolfi
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ABSTRACT: GATA-1-dependent transcription is essential for erythroid differentiation and maturation. Suppression of programmed cell death is also thought to be critical for this process; however, the link between these two features of erythropoiesis has remained elusive. Here, we show that the POZ-Krüppel family transcription factor, LRF (also known as Zbtb7a/Pokemon), is a direct target of GATA1 and plays an essential antiapoptotic role during terminal erythroid differentiation. We find that loss of Lrf leads to lethal anemia in embryos, due to increased apoptosis of late-stage erythroblasts. This programmed cell death is Arf and p53 independent and is instead mediated by upregulation of the proapoptotic factor Bim. We identify Lrf as a direct repressor of Bim transcription. In strong support of this mechanism, genetic Bim loss delays the lethality of Lrf-deficient embryos and rescues their anemia phenotype. Thus, our data define a key transcriptional cascade for effective erythropoiesis, whereby GATA-1 suppresses BIM-mediated apoptosis via LRF.
Developmental cell 10/2009; 17(4):527-40. · 13.36 Impact Factor
