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1.
《Protein science : a publication of the Protein Society》2018,27(8):1491-1497
Recent studies have demonstrated that the O‐antigens of some pathogenic bacteria such as Brucella abortus, Francisella tularensis, and Campylobacter jejuni contain quite unusual N‐formylated sugars (3‐formamido‐3,6‐dideoxy‐d ‐glucose or 4‐formamido‐4,6‐dideoxy‐d ‐glucose). Typically, four enzymes are required for the formation of such sugars: a thymidylyltransferase, a 4,6‐dehydratase, a pyridoxal 5'‐phosphate or PLP‐dependent aminotransferase, and an N‐formyltransferase. To date, there have been no published reports of N‐formylated sugars associated with Mycobacterium tuberculosis. A recent investigation from our laboratories, however, has demonstrated that one gene product from M. tuberculosis, Rv3404c, functions as a sugar N‐formyltransferase. Given that M. tuberculosis produces l ‐rhamnose, both a thymidylyltransferase (Rv0334) and a 4,6‐dehydratase (Rv3464) required for its formation have been identified. Thus, there is one remaining enzyme needed for the production of an N‐formylated sugar in M. tuberculosis, namely a PLP‐dependent aminotransferase. Here we demonstrate that the M. tuberculosis rv3402c gene encodes such an enzyme. Our data prove that M. tuberculosis contains all of the enzymatic activities required for the formation of dTDP‐4‐formamido‐4,6‐dideoxy‐d ‐glucose. Indeed, the rv3402c gene product likely contributes to virulence or persistence during infection, though its temporal expression and location remain to be determined. 相似文献
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Yosuke Suzuki Hiroki Itoh Fumihiko Katagiri Fuminori Sato Kanako Kawasaki Yuhki Sato Hiromitsu Mimata Masaharu Takeyama 《Journal of peptide science》2012,18(4):276-281
N‐acetyl‐seryl‐aspartyl‐lysyl‐proline (AcSDKP) is a natural inhibitor of pluripotent hematopoietic stem cell proliferation and is normally found in human plasma. Because AcSDKP is hydrolyzed by the N‐terminal active site of angiotensin converting enzyme and partially eliminated in urine, its plasma level is a result of a complex balance between its production, hydrolysis by ACE, and renal elimination. In this study, we attempted to establish an enzyme immunoassay (EIA) for quantifying AcSDKP‐like immunoreactive substance (IS), which is applicable for monitoring plasma AcSDKP levels in healthy subjects and patients with chronic renal failure. Using β‐ d ‐galactosidase‐labeled Gly‐γAbu‐SDKP as a marker antigen, an anti‐rabbit IgG‐coated immunoplate as a bound/free separator and 4‐methylumbelliferyl‐β‐ d ‐galactopyranoside as a fluorogenic substrate, a highly sensitive and specific EIA was developed for the quantification of AcSDKP‐IS in human plasma. The lower limit of quantification was 0.32 fmol/well, and the sharp inhibition competitive EIA calibration curve obtained was linear between 8.0 and 513 fmol/ml. This EIA was so sensitive that only 10 µl plasma sample was required for a single assay. The coefficients of variation (reproducibility) for human plasma concentrations of 0.2 and 2.1 pmol/ml were 7.2 and 7.7%, respectively, for inter‐assay and 13.3 and 7.8% for intra‐assay comparisons. Plasma AcSDKP‐IS level was significantly higher in patients with chronic renal failure (0.92 ± 0.39 pmol/ml) compared with healthy subjects (0.29 ± 0.07 pmol/ml). These results suggest that our EIA may be useful to evaluate plasma AcSDKP level as a biomarker in various patients. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
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Matthias Hackl Stefan Brunner Klaus Fortschegger Carina Schreiner Lucia Micutkova Christoph Mück Gerhard T. Laschober Günter Lepperdinger Natalie Sampson Peter Berger Dietmar Herndler‐Brandstetter Matthias Wieser Harald Kühnel Alois Strasser Mark Rinnerthaler Michael Breitenbach Michael Mildner Leopold Eckhart Erwin Tschachler Andrea Trost Johann W. Bauer Christine Papak Zlatko Trajanoski Marcel Scheideler Regina Grillari‐Voglauer Beatrix Grubeck‐Loebenstein Pidder Jansen‐Dürr Johannes Grillari 《Aging cell》2010,9(2):291-296
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Yvonne Piotrowski Guido Hansen A. Linda Boomaars‐van der Zanden Eric J. Snijder Alexander E. Gorbalenya Rolf Hilgenfeld 《Protein science : a publication of the Protein Society》2009,18(1):6-16
The polyproteins of coronaviruses are cleaved by viral proteases into at least 15 nonstructural proteins (Nsps). Consisting of five domains, Nsp3 is the largest of these (180–210 kDa). Among these domains, the so‐called X‐domain is believed to act as ADP‐ribose‐1″‐phosphate phosphatase or to bind poly(ADP‐ribose). However, here we show that the X‐domain of Infectious Bronchitis Virus (strain Beaudette), a Group‐3 coronavirus, fails to bind ADP‐ribose. This is explained on the basis of the crystal structure of the protein, determined at two different pH values. For comparison, we also describe the crystal structure of the homologous X‐domain from Human Coronavirus 229E, a Group‐1 coronavirus, which does bind ADP‐ribose. 相似文献
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Blanca M. Santoyo Carlos Gonzlez‐Romero Daniel Zrate‐Zrate R. Israel Hernndez‐Benitez Vanessa Pelayo Edson Barrera Carlos H. Escalante Ayde Fuentes‐Benites Guadalupe Martínez‐Morales Julio Lpez Miguel A. Vzquez Francisco Delgado Hugo A. Jimnez‐Vzquez Joaquín Tamariz 《Chirality》2019,31(9):719-749
Enantiopure 3‐((R)‐ and 3‐((S)‐1‐phenylethyl)‐4‐oxazoline‐2‐ones were evaluated as chiral building blocks for the divergent construction of heterocycles with stereogenic quaternary centers. The N‐(R)‐ or N‐(S)‐1‐phenylethyl group of these compounds proved to be an efficient chiral auxiliary for the asymmetric induction of the 4‐ and 5‐positions of the 4‐oxazolin‐2‐one ring through thermal and MW‐promoted nucleophilic conjugated addition to Michael acceptors and alkyl halides. The resulting adducts were transformed via a cascade process into fused six‐membered carbo‐ and heterocycles. The structure of the reaction products depended on the electrophiles and reaction conditions used. Alternative isomeric 4‐methylene‐2‐oxazolidinones served as chiral precursors for a versatile and divergent approach to highly substituted cyclic carbamates. DFT quantum calculations showed that the formation of bicyclic pyranyl compounds was generated by a diastereoselective concerted hetero‐Diels‐Alder cycloaddition. 相似文献
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20‐O‐β‐d‐Glucopyranosyl‐20(S)‐Protopanaxadiol Suppresses UV‐Induced MMP‐1 Expression Through AMPK‐Mediated mTOR Inhibition as a Downstream of the PKA‐LKB1 Pathway 下载免费PDF全文
Dong Joo Shin Jong‐Eun Kim Tae‐Gyu Lim Eun Hee Jeong Gaeun Park Nam Joo Kang Jun‐Seong Park Myeong‐Hun Yeom Deok Kun Oh Ann M. Bode Zigang Dong Hyong Joo Lee Ki Won Lee 《Journal of cellular biochemistry》2014,115(10):1702-1711
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Hidehisa Kawashima Nobuko Watanabe Hisako K. Ijuin Masakatsu Matsumoto 《Luminescence》2013,28(5):696-704
Bicyclic dioxetanes 2a–c bearing a 2′‐alkoxy‐2‐hydroxy‐1,1′‐binaphthyl‐7‐yl moiety were effectively synthesized and their base‐induced chemiluminescent decomposition was investigated by the use of alkaline metal (Na+ and K+) or Mg2+ alkoxide in MeOH. When 2a–c were treated with tetrabutylammonium fluoride (TBAF) in dimethyl sulfoxide (DMSO) as a reference system, they showed chemiluminescence as a flash of orange light (maximum wavelength λmaxCL = 573–577 nm) with efficiency ΦCL = 6–8 × 10–2. On the other hand, for an alkaline metal (Na+ or K+) alkoxide/MeOH system, 2a–c decomposed slowly to emit a glow of chemiluminescence, the spectra of which were shifted slightly toward red from the TBAF/DMSO system, and ΦCL (= 1.4–2.3 × 10–3) was considerably decreased. In addition, Mg(OMe)2 was found to play a characteristic role as a base for the chemiluminescent decomposition of 2a–c through coordination to the intermediary oxidoaryl‐substituted dioxetanes 13. Thus, Mg2+ increased ΦCL to more than twice those with Na+ or K+, while it shifted λmaxCL considerably toward blue (λmaxCL = 550–566 nm). Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
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Washing is a standard step for enzyme‐linked immunosorbent assays (ELISA) performed on a paper‐based chip, in which nonspecific‐binding antibodies and antigens should be removed completely from the paper surface. In this study, a novel three‐dimensional (3D) washing strategy using a heating ring‐oven was carried out on a paper‐based chip. Compared with a plane washing mode by a ring‐oven, this 3D washing strategy obtained a lower background, as gravity played an important role in the washing step. The paper‐based chip was placed on a 3D plastic holder and the waste area was connected to a heating ring. Use of a heating waste area meant that the nonspecific‐binding protein was continuously carried to the waste area through gravity and capillary action. The angle between the plastic holder and the ring plane was carefully selected. The effect of washing on different parts of the detection area was investigated by upconversion fluorescence and chemiluminescence (CL). This novel 3D washing strategy was performed for carcinoembryonic antigen detection through CL and a lower detection limit of 2 pg ml?1 was obtained. This approach provides an effective washing strategy to remove nonspecific‐binding antibody from a paper‐based immunodevice. 相似文献
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Ecologically mediated selection has increasingly become recognised as an important driver of speciation. The correlation between neutral genetic differentiation and environmental or phenotypic divergence among populations, to which we collectively refer to as isolation‐by‐ecology (IBE), is an indicator of ecological speciation. In a meta‐analysis framework, we determined the strength and commonality of IBE in nature. On the basis of 106 studies, we calculated a mean effect size of IBE with and without controlling for spatial autocorrelation among populations. Effect sizes were 0.34 (95% CI 0.24–0.42) and 0.26 (95% CI 0.13–0.37), respectively, indicating that an average of 5% of the neutral genetic differentiation among populations was explained purely by ecological contrast. Importantly, spatial autocorrelation reduced IBE correlations for environmental variables, but not for phenotypes. Through simulation, we showed how the influence of isolation‐by‐distance and spatial autocorrelation of ecological variables can result in false positives or underestimated correlations if not accounted for in the IBE model. Collectively, this meta‐analysis showed that ecologically induced genetic divergence is pervasive across time‐scales and taxa, and largely independent of the choice of molecular marker. We discuss the importance of these results in the context of adaptation and ecological speciation and suggest future research avenues. 相似文献
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Cheryl A. Conover 《Aging cell》2010,9(6):942-946
This article focuses on the role of PAPP‐A in mammalian aging. It introduces PAPP‐A and a little of its history, briefly discusses the function of PAPP‐A in the insulin‐like growth factor (IGF) system and the regulators of PAPP‐A expression, and then reviews data concerning PAPP‐A in aging and age‐related diseases especially in regard to the PAPP‐A knockout (KO) mouse. The PAPP‐A KO mouse is a valuable new model to test hypotheses concerning the control of the tissue availability of IGF, independent from systemic levels, on healthspan as well as lifespan. 相似文献
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This study is aimed at elucidating the structure of a novel T‐cell adhesion inhibitor, cyclo(1,8)‐CPRGGSVC using one‐ and two‐dimensional (2D) 1H NMR and molecular dynamics (MD) simulation. The peptide is derived from the sequence of its parent peptide cIBR (cyclo(1,12)‐PenPRGGSVLVTGC), which is a fragment of intercellular adhesion molecule‐1 (ICAM‐1). Our previous results show that the cyclo(1,8)‐CPRGGSVC peptide binds to the LFA‐1 I‐domain and inhibits heterotypic T‐cell adhesion, presumably by blocking the LFA‐1/ICAM‐1 interactions. The structure of the peptide was determined using NMR and MD simulation in aqueous solution. Our results indicate that the peptide adopts type‐I β‐turn conformation at the Pro2‐Arg3‐Gly4‐Gly5 (PRGG) sequence. The β‐turn structure at the PRGG motif is well conserved in cIBR peptide and ICAM‐1 receptor, which suggests the importance of the PRGG motif for the biological activity of cyclo(1,8)‐CPRGGSVC peptide. Meanwhile, the Gly5‐Ser6‐Val7‐Cys8‐Cys1 (GSVCC) sequence forms a “turn‐like” random coil structure that does not belong to any structured motif. Therefore, cyclo(1,8)‐CPRGGSVC peptide has only one structured region at the PRGG sequence, which may play an important role in the binding of the peptide to the LFA‐1 I‐domain. The conserved β‐turn conformation of the PRGG motif in ICAM‐1, cIBR, and cyclo(1,8)‐CPRGGSVC peptides can potentially be used to design peptidomimetics. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 633–641, 2009. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com 相似文献
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7,8‐Dihydroxy‐9,10‐epoxy‐7,8,9,10‐tetrahydrobenzo[a]pyrene (BPDE) exposure induces adduct formation and oxidative damage on DNA, and consequently triggers complicated stress responses, including such responses as signaling pathway activation, cell cycle arrest, DNA repair, translesion DNA synthesis and mutagenesis. In the present study, 2‐DE and MALDI‐TOF MS were employed to analyze the differential extracellular protein patterns of human amniotic epithelial cells (FL cells) after exposure to 5 nM BPDE and control. As a result, one protein spot that appeared in the culture medium of BPDE treatment group was successfully identified as 14‐3‐3ζ, and three up‐regulated protein spots were identified as annexin A3, annexin V and hydroxypyruvate isomerase homolog. Among them, 14‐3‐3ζ was further detected in some pleural fluid specimens also. These results demonstrate that BPDE exposure can induce alterations of extracellular protein profiles of exposed cells, which may be served as a starting point for searching candidate biomarkers for benzo[a]pyrene exposure. 相似文献
15.
Pim Cuijpers Eirini Karyotaki Mirjam Reijnders Marianna Purgato Corrado Barbui 《World psychiatry》2018,17(1):90-101
Most psychotherapies for depression have been developed in high‐income Western countries of North America, Europe and Australia. A growing number of randomized trials have examined the effects of these treatments in non‐Western countries. We conducted a meta‐analysis of these studies to examine whether these psychotherapies are effective and to compare their effects between studies from Western and non‐Western countries. We conducted systematic searches in bibliographical databases and included 253 randomized controlled trials, of which 32 were conducted in non‐Western countries. The effects of psychotherapies in non‐Western countries were large (g=1.10; 95% CI: 0.91‐1.30), with high heterogeneity (I2=90; 95% CI: 87‐92). After adjustment for publication bias, the effect size dropped to g=0.73 (95% CI: 0.51‐0.96). Subgroup analyses did not indicate that adaptation to the local situation was associated with the effect size. Comparisons with the studies in Western countries showed that the effects of the therapies were significantly larger in non‐Western countries, also after adjusting for characteristics of the participants, the treatments and the studies. These larger effect sizes in non‐Western countries may reflect true differences indicating that therapies are indeed more effective; or may be explained by the care‐as‐usual control conditions in non‐Western countries, often indicating that no care was available; or may be the result of the relative low quality of many trials in the field. This study suggests that psychotherapies that were developed in Western countries may or may not be more effective in non‐Western countries, but they are probably no less effective and can therefore also be used in these latter countries. 相似文献
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4‐Cyano‐α‐methyl‐l‐phenylalanine as a Spectroscopic Marker for the Investigation of PeptaibioticMembrane Interactions 下载免费PDF全文
Marta De Zotti Sara Bobone Annalisa Bortolotti Edoardo Longo Barbara Biondi Cristina Peggion Fernando Formaggio Claudio Toniolo Andrea Dalla Bona Bernard Kaptein Lorenzo Stella 《化学与生物多样性》2015,12(4):513-527
Two analogs of the ten‐amino acid residue, membrane‐active lipopeptaibiotic trichogin GA IV, mono‐labeled with 4‐cyano‐α‐methyl‐L ‐phenylalanine, a potentially useful fluorescence and IR absorption probe of the local microenvironment, were synthesized by the solid‐phase methodology and conformationally characterized. The single modification was incorporated either at the N‐terminus (position 1) or near the C‐terminus (position 8) of the peptide main chain. In both cases, the replaced amino acid was the equally helicogenic α‐aminoisobutyric acid (Aib) residue. We performed a solution conformational analysis by use of FT‐IR absorption, CD, and 2D‐NMR spectroscopies. The results indicate that both labeled analogs essentially maintain the overall helical propensity of the naturally occurring lipopeptaibiotic. Peptide? membrane interactions were assessed by fluorescence and ATR‐IR absorption techniques. Analogies and differences between the two peptides were highlighted. Taken together, our data confirm literature results that some of the spectroscopic parameters of the 4‐cyanobenzyl chromophore are sensitive markers of the local microenvironment. 相似文献
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Large‐scale synthesis of tert‐butyl (3R,5S)‐6‐chloro‐3,5‐dihydroxyhexanoate by a stereoselective carbonyl reductase with high substrate concentration and product yield 下载免费PDF全文
Zhi‐Qiang Liu Zhong‐Liang Hu Xiao‐Jian Zhang Xiao‐Ling Tang Feng Cheng Ya‐Ping Xue Ya‐Jun Wang Lin Wu Dan‐Kai Yao Yi‐Teng Zhou Yu‐Guo Zheng 《Biotechnology progress》2017,33(3):612-620
To biosynthesize the (3R,5S)‐CDHH in an industrial scale, a newly synthesized stereoselective short chain carbonyl reductase (SCR) was successfully cloned and expressed in Escherichia coli. The fermentation of recombinant E. coli harboring SCR was carried out in 500 L and 5000 L fermenters, with biomass and specific activity of 9.7 g DCW/L, 15749.95 U/g DCW, and 10.97 g DCW/L, 19210.12 U/g DCW, respectively. The recombinant SCR was successfully applied for efficient production of (3R,5S)‐CDHH. The scale‐up synthesis of (3R,5S)‐CDHH was performed in 5000 L bioreactor with 400 g/L of (S)‐CHOH at 30°C, resulting in a space‐time yield of 13.7 mM/h/g DCW, which was the highest ever reported. After isolation and purification, the yield and d.e. of (3R,5S)‐CDHH reached 97.5% and 99.5%, respectively. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:612–620, 2017 相似文献
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Alex L. Zimmer James B. Thoden Hazel M. Holden 《Protein science : a publication of the Protein Society》2014,23(3):273-283
N‐formylated sugars have been observed on the O‐antigens of such pathogenic Gram‐negative bacteria as Campylobacter jejuni and Francisella tularensis. Until recently, however, little was known regarding the overall molecular architectures of the N‐formyltransferases that are required for the biosynthesis of these unusual sugars. Here we demonstrate that the protein encoded by the wbtj gene from F. tularensis is an N‐formyltransferase that functions on dTDP‐4‐amino‐4,6‐dideoxy‐d ‐glucose as its substrate. The enzyme, hereafter referred to as WbtJ, demonstrates a strict requirement for N10‐formyltetrahydrofolate as its carbon source. In addition to the kinetic analysis, the three‐dimensional structure of the enzyme was solved in the presence of dTDP‐sugar ligands to a nominal resolution of 2.1 Å. Each subunit of the dimeric enzyme is dominated by a “core” domain defined by Met 1 to Ser 185. This core motif harbors the active site residues. Following the core domain, the last 56 residues fold into two α‐helices and a β‐hairpin motif. The hairpin motif is responsible primarily for the subunit:subunit interface, which is characterized by a rather hydrophobic pocket. From the study presented here, it is now known that WbtJ functions on C‐4′ amino sugars. Another enzyme recently investigated in the laboratory, WlaRD, formylates only C‐3′ amino sugars. Strikingly, the quaternary structures of WbtJ and WlaRD are remarkably different. In addition, there are several significant variations in the side chains that line their active site pockets, which may be important for substrate specificity. Details concerning the kinetic and structural properties of WbtJ are presented. 相似文献