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41.
Kovári J Barabás O Varga B Békési A Tölgyesi F Fidy J Nagy J Vértessy BG 《Proteins》2008,71(1):308-319
dUTP pyrophosphatase, a preventive DNA repair enzyme, contributes to maintain the appropriate cellular dUTP/dTTP ratio by catalyzing dUTP hydrolysis. dUTPase is essential for viability in bacteria and eukaryotes alike. Identification of species-specific antagonists of bacterial dUTPases is expected to contribute to the development of novel antimicrobial agents. As a first general step, design of dUTPase inhibitors should be based on modifications of the substrate dUTP phosphate chain, as modifications in either base or sugar moieties strongly impair ligand binding. Based on structural differences between bacterial and human dUTPases, derivatization of dUTP-analogous compounds will be required as a second step to invoke species-specific character. Studies performed with dUTP analogues also offer insights into substrate binding characteristics of this important and structurally peculiar enzyme. In this study, alpha,beta-methylene-dUDP was synthesized and its complex with dUTPase was characterized. Enzymatic phosphorylation of this substrate analogue by pyruvate kinase was not possible in contrast to the successful enzymatic phosphorylation of alpha,beta-imino-dUDP. One explanation for this finding is that the different bond angles and the presence of the methylene group may preclude formation of a catalytically competent complex with the kinase. Crystal structure of E. coli dUTPase:alpha,beta-methylene-dUDP and E. coli dUTPase:dUDP:Mn complexes were determined and analyzed in comparison with previous data. Results show that the "trans" alpha-phosphate conformation of alpha,beta-methylene-dUDP differs from the catalytically competent "gauche" alpha-phosphate conformation of the imino analogue and the oxo substrate, manifested in the shifted position of the alpha-phosphorus by more than 3 A. The three-dimensional structures determined in this work show that the binding of the methylene analogue with the alpha-phosphorus in the "gauche" conformation would result in steric clash of the methylene group with the protein atoms. In addition, the metal ion cofactor was not bound in the crystal of the complex with the methylene analogue while it was clearly visible as coordinated to dUDP, arguing that the altered phosphate chain conformation also perturbs metal ion complexation. Isothermal calorimetry titrations indicate that the binding affinity of alpha,beta-methylene-dUDP toward dUTPase is drastically decreased when compared with that of dUDP. In conclusion, the present data suggest that while alpha,beta-methylene-dUDP seems to be practically nonhydrolyzable, it is not a strong binding inhibitor of dUTPase probably due to the altered binding mode of the phosphate chain. Results indicate that in some cases methylene analogues may not faithfully reflect the competent substrate ligand properties, especially if the methylene hydrogens are in steric conflict with the protein. 相似文献
42.
Orsolya Toke Zoltán Bánóczi Gábor Tárkányi Péter Friedrich Ferenc Hudecz 《Journal of peptide science》2009,15(6):404-410
Calpastatin, the endogenous inhibitor of calpain, a cysteine protease in eukaryotic cells, is an intrinsically unstructured protein, which upon binding to the enzyme goes through a conformational change. Peptides calpA (SGKSGMDAALDDLIDTLGG) and calpC (SKPIGPDDAIDALSSDFTS), corresponding to the two conserved subdomains of calpastatin, are known to activate calpain and increase the Ca2+ sensitivity of the enzyme. Using solution NMR spectroscopy, here we show that calpA and calpC are disordered in water but assume an α‐helical conformation in 50% CD3OH. The position and length of the helices are in agreement with those described in the literature for the bound state of the corresponding segments of calpastatin suggesting that the latter might be structurally primed for the interaction with its target. According to our data, the presence of Ca2+ induces a backbone rearrangement in the peptides, an effect that may contribute to setting the fine conformational balance required for the interaction of the peptides with calpain. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
43.
Dangeruta Kersulyte WooKon Lee Dharmalingam Subramaniam Shrikant Anant Phabiola Herrera Lilia Cabrera Jacqueline Balqui Orsolya Barabas Awdhesh Kalia Robert H. Gilman Douglas E. Berg 《PloS one》2009,4(9)
Background
Genes present in only certain strains of a bacterial species can strongly affect cellular phenotypes and evolutionary potentials. One segment that seemed particularly rich in strain-specific genes was found by comparing the first two sequenced Helicobacter pylori genomes (strains 26695 and J99) and was named a “plasticity zone”.Principal Findings
We studied the nature and evolution of plasticity zones by sequencing them in five more Helicobacter strains, determining their locations in additional strains, and identifying them in recently released genome sequences. They occurred as discrete units, inserted at numerous chromosomal sites, and were usually flanked by direct repeats of 5′AAGAATG, a sequence generally also present in one copy at unoccupied sites in other strains. This showed that plasticity zones are transposable elements, to be called TnPZs. Each full length TnPZ contained a cluster of type IV protein secretion genes (tfs3), a tyrosine recombinase family gene (“xerT”), and a large (≥2800 codon) orf encoding a protein with helicase and DNA methylase domains, plus additional orfs with no homology to genes of known function. Several TnPZ types were found that differed in gene arrangement or DNA sequence. Our analysis also indicated that the first-identified plasticity zones (in strains 26695 and J99) are complex mosaics of TnPZ remnants, formed by multiple TnPZ insertions, and spontaneous and transposable element mediated deletions. Tests using laboratory-generated deletions showed that TnPZs are not essential for viability, but identified one TnPZ that contributed quantitatively to bacterial growth during mouse infection and another that affected synthesis of proinflammatory cytokines in cell culture.Conclusions
We propose that plasticity zone genes are contained in conjugative transposons (TnPZs) or remnants of them, that TnPZ insertion is mediated by XerT recombinase, and that some TnPZ genes affect bacterial phenotypes and fitness. 相似文献44.
45.
Parental cooperation in a changing climate: fluctuating environments predict shifts in care division
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Orsolya Vincze András Kosztolányi Zoltán Barta Clemens Küpper Monif Alrashidi Juan A. Amat Araceli Argüelles Ticó Fiona Burns John Cavitt Warren C. Conway Medardo Cruz‐López Atahualpa Eduardo Desucre‐Medrano Natalie dos Remedios Jordi Figuerola Daniel Galindo‐Espinosa Gabriel E. García‐Peña Salvador Gómez Del Angel Cheri Gratto‐Trevor Paul Jönsson Penn Lloyd Tomás Montalvo Jorge Enrique Parra Raya Pruner Pinjia Que Yang Liu Sarah T. Saalfeld Rainer Schulz Lorenzo Serra James J. H. St Clair Lynne E. Stenzel Michael A. Weston Maï Yasué Sama Zefania Tamás Székely 《Global Ecology and Biogeography》2017,26(3):347-358
46.
Synthesis of new 2-amino-2-C-d-glycosyl-acetonitriles in a Strecker reaction from various C-glycosyl aldehydes, chiral amines, and HCN was carried out. While aminonitriles from glycal and 2-deoxy-β-d-glycosyl aldehydes were prepared in satisfactory yields, lower yields were obtained with C-glycosyl aldehydes. Strecker reaction with the benzyl-protected 1-C-formyl-d-galactal and S- or R-1-phenylethylamine (S-PEA or R-PEA) yielded predominantly the R-configured C-glycosyl aminoacetonitrile. The direction of the nucleophilic addition appears to be governed by the configuration of the anomeric carbon with β-linked sugars. Since the stereochemistry of the transition state is unknown according to the configuration of the major product a Felkin–Ahn selectivity can be mainly presumed. 相似文献
47.
Salicylic acid and photosynthesis: signalling and effects 总被引:1,自引:0,他引:1
Tibor Janda Orsolya Kinga Gondor Rusina Yordanova Gabriella Szalai Magda Pál 《Acta Physiologiae Plantarum》2014,36(10):2537-2546
Salicylic acid (SA) is a well-known signalling molecule playing a role in local and systemic acquired resistance against pathogens as well as in acclimation to certain abiotic stressors. As a stress-related signalling compound, it may directly or indirectly affect various physiological processes, including photosynthesis. The effects of exogenously applied SA on plant physiological processes under optimal environmental conditions are controversial. Several studies suggest that SA may have a positive effect on germination or plant growth in various plant species. However, SA may also act as a stress factor, having a negative influence on various physiological processes. Its mode of action depends greatly on several factors, such as the plant species, the environmental conditions (light, temperature, etc.) and the concentration. Exogenous SA may also alleviate the damaging effects of various stress factors, and this protection may also be manifested as higher photosynthetic capacity. Unfavourable environmental conditions have also been shown to increase the endogenous SA level in plants. Recent results strongly suggest that controlled SA levels are important in plants for optimal photosynthetic performance and for acclimation to changing environmental stimuli. The present review discusses the effects of exogenous and endogenous SA on the photosynthetic processes under optimal and stress conditions. 相似文献
48.
Makardhwaj S Shrivastava Zulfiqar Hussain Orsolya Giricz Niraj Shenoy Rahul Polineni Anirban Maitra 《Cell cycle (Georgetown, Tex.)》2014,13(21):3320-3327
Esophageal adenocarcinoma (EAC) is one of the fastest growing malignancies in the US and needs newer therapeutic and diagnostic strategies. Chronic inflammation plays a role in the pathogenesis of EAC and contributes to the dysplastic conversion of normal esophageal epithelium to Barrett's esophagus and frank adenocarcinoma. Chemokines play important roles in mediating inflammation and recent evidence implicates these ligands and their receptors in the development and spread of various tumors. We demonstrated that the chemokines IL8, CXCL1 and CXCL3 are significantly overexpressed during esophageal carcinogenesis and accompanied by amplification and demethylation of the chr4q21 gene locus. We also demonstrated that IL8 levels can be detected in serum of patients with EAC and can serve as potential biomarkers. We now demonstrate that inhibition of IL8 receptor, CXCR2, leads to decreased invasiveness of esophageal adenocarcinoma derived cells without affecting cellular proliferation. Taken together, these studies reveal the important roles that chemokines play in development of esophageal cancer and demonstrate that these pathways can serve as potential therapeutic targets. 相似文献
49.
Extensively managed pastures are of crucial importance in sustaining biodiversity both in local- and landscape-level. Thus, re-introduction of traditional grazing management is a crucial issue in grassland conservation actions worldwide. Traditional grazing with robust cattle breeds in low stocking rates is considered to be especially useful to mimic natural grazing regimes, but well documented case-studies are surprisingly rare on this topic. Our goal was to evaluate the effectiveness of traditional Hungarian Grey cattle grazing as a conservation action in a mosaic alkali landscape. We asked the following questions: (i) How does cattle grazing affect species composition and diversity of the grasslands? (ii) What are the effects of grazing on short-lived and perennial noxious species? (iii) Are there distinct effects of grazing in dry-, mesophilous- and wet grassland types? Vegetation of fenced and grazed plots in a 200-ha sized habitat complex (secondary dry grasslands and pristine mesophilous- and wet alkali grasslands) was sampled from 2006–2009 in East-Hungary. We found higher diversity scores in grazed plots compared to fenced ones in mesophilous- and wet grasslands. Higher cover of noxious species was typical in fenced plots compared to their grazed counterparts in the last year in every studied grassland type. We found an increasing effect of grazing from the dry- towards the wet grassland types. The year-to-year differences also followed similar pattern: the site-dependent effects were the lowest in the dry grassland and an increasing effect was detected along the moisture gradient. We found that extensive Hungarian Grey cattle grazing is an effective tool to suppress noxious species and to create a mosaic vegetation structure, which enables to maintain high species richness in the landscape. Hungarian Grey cattle can feed in open habitats along long moisture gradient, thus in highly mosaic landscapes this breed can be the most suitable livestock type. 相似文献
50.
Hubert Korr Nicholas B. Angstman Tatjana B. Born Kerstin Bosse Birka Brauns Martin Demmler Katja Fueller Orsolya Kántor Barbara M. Kever Navida Rahimyar Sepideh Salimi Jiri Silny Christoph Schmitz 《PloS one》2014,9(10)