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991.
Agnieszka Paziewska Bozena Cukrowska Michalina Dabrowska Krzysztof Goryca Magdalena Piatkowska Anna Kluska Michal Mikula Jakub Karczmarski Beata Oralewska Anna Rybak Jerzy Socha Aneta Balabas Natalia Zeber-Lubecka Filip Ambrozkiewicz Ewa Konopka Ilona Trojanowska Malgorzata Zagroba Malgorzata Szperl Jerzy Ostrowski 《PloS one》2015,10(9)
Assessment of non-HLA variants alongside standard HLA testing was previously shown to improve the identification of potential coeliac disease (CD) patients. We intended to identify new genetic variants associated with CD in the Polish population that would improve CD risk prediction when used alongside HLA haplotype analysis. DNA samples of 336 CD and 264 unrelated healthy controls were used to create DNA pools for a genome wide association study (GWAS). GWAS findings were validated with individual HLA tag single nucleotide polymorphism (SNP) typing of 473 patients and 714 healthy controls. Association analysis using four HLA-tagging SNPs showed that, as was found in other populations, positive predicting genotypes (HLA-DQ2.5/DQ2.5, HLA-DQ2.5/DQ2.2, and HLA-DQ2.5/DQ8) were found at higher frequencies in CD patients than in healthy control individuals in the Polish population. Both CD-associated SNPs discovered by GWAS were found in the CD susceptibility region, confirming the previously-determined association of the major histocompatibility (MHC) region with CD pathogenesis. The two most significant SNPs from the GWAS were rs9272346 (HLA-dependent; localized within 1 Kb of DQA1) and rs3130484 (HLA-independent; mapped to MSH5). Specificity of CD prediction using the four HLA-tagging SNPs achieved 92.9%, but sensitivity was only 45.5%. However, when a testing combination of the HLA-tagging SNPs and the MSH5 SNP was used, specificity decreased to 80%, and sensitivity increased to 74%. This study confirmed that improvement of CD risk prediction sensitivity could be achieved by including non-HLA SNPs alongside HLA SNPs in genetic testing. 相似文献
992.
Jiří Šponer Michal Sabat Jaroslav V. Burda Jerzy Leszczynski Pavel Hobza Bernhard Lippert 《Journal of biological inorganic chemistry》1999,4(5):537-545
Ab initio calculations have been carried out to characterize the structure and energetics of a silver(I) complex with the
cytosine-adenine DNA base pair and an aqua ligand in the coordination sphere of Ag. In addition, we have also studied analogous
complexes with Cu(I) and Au(I), and structures in which adenine has been replaced by purine in order to investigate the structural
role of the adenine amino group. The calculations revealed that all metal-modified structures are dominated by the metal-base
interactions, while the water-metal ion interaction and many-body interligand repulsion are less important contributions.
Nevertheless, the structural role of the water molecule in the complex is quite apparent and in agreement with an earlier
crystallographic study. The metal-modified base pairs exhibit large conformational flexibility toward out-of-plane motions
(propeller twist and buckle), comparable or, in some cases, even larger than that observed in the base pairs without metal
ions. All structures have been optimized within the Hartree-Fock approximation, while interaction energies were evaluated
with the inclusion of electron correlation.
Received: 25 March 1999 / Accepted: 10 June 1999 相似文献
993.
994.
Olexandr Isayev Carlos E. Crespo‐Hernández Leonid Gorb Frances C. Hill Jerzy Leszczynski 《Proteins》2012,80(12):2728-2741
Reduction, catalyzed by the bacterial nitroreductases, is the quintessential first step in the biodegradation of a variety of nitroaromatic compounds from contaminated waters and soil. The Enterobacter cloacae nitroreductase (EcNR) enzyme is considered as a prospective biotechnological tool for bioremediation of hazardous nitroaromatic compounds. Using diverse computational methods, we obtain insights into the structural basis of activity and mechanism of its function. We have performed molecular dynamics simulation of EcNR in three different states (free EcNR in oxidized form, fully reduced EcNR with benzoate inhibitor and fully reduced EcNR with nitrobenzene) in explicit solvent and with full electrostatics. Principal Component Analysis (PCA) of the variance‐covariance matrix showed that the complexed nitroreductase becomes more flexible overall upon complexation, particularly helix H6, in the vicinity of the binding site. A multiple sequence alignment was also constructed in order to examine positional constraints on substitution in EcNR. Five regions which are highly conserved within the flavin mononucleotide (FMN) binding site were identified. Obtained results and their implications for EcNR functioning are discussed, and new plausible mechanism has been proposed. Proteins 2012; © 2012 Wiley Periodicals, Inc. 相似文献
995.
996.
Ciesielski SJ Schilke BA Osipiuk J Bigelow L Mulligan R Majewska J Joachimiak A Marszalek J Craig EA Dutkiewicz R 《Journal of molecular biology》2012,417(1-2):1-12
The ubiquitous mitochondrial J-protein Jac1, called HscB in Escherichia coli, and its partner Hsp70 play a critical role in the transfer of Fe-S clusters from the scaffold protein Isu to recipient proteins. Biochemical results from eukaryotic and prokaryotic systems indicate that formation of the Jac1-Isu complex is important for both targeting of the Isu for Hsp70 binding and stimulation of Hsp70's ATPase activity. However, in apparent contradiction, we previously reported that an 8-fold decrease in Jac1's affinity for Isu1 is well tolerated in vivo, raising the question as to whether the Jac1:Isu interaction actually plays an important biological role. Here, we report the determination of the structure of Jac1 from Saccharomyces cerevisiae. Taking advantage of this information and recently published data from the homologous bacterial system, we determined that a total of eight surface-exposed residues play a role in Isu binding, as assessed by a set of biochemical assays. A variant having alanines substituted for these eight residues was unable to support growth of a jac1-Δ strain. However, replacement of three residues caused partial loss of function, resulting in a significant decrease in the Jac1:Isu1 interaction, a slow growth phenotype, and a reduction in the activity of Fe-S cluster-containing enzymes. Thus, we conclude that the Jac1:Isu1 interaction plays an indispensable role in the essential process of mitochondrial Fe-S cluster biogenesis. 相似文献
997.
In the present study, we have performed comparative analysis of different prenyllipids in Chlamydomonas reinhardtii cultures during high light stress under variety of conditions (presence of inhibitors, an uncoupler, heavy water). The obtained results indicate that plastoquinol is more active than α-tocopherol in scavenging of singlet oxygen generated in photosystem II. Besides plastoquinol, also its oxidized form, plastoquinone shows antioxidant action during the stress conditions, resulting in formation of plastoquinone-C, whose level can be regarded as an indicator of singlet oxygen oxidative stress in vivo. The pronounced stimulation of α-tocopherol consumption and α-tocopherolquinone formation by an uncoupler, FCCP, together with the results of additional model system studies, led to the suggestion that α-tocopherol can be recycled in thylakoid membranes under high light conditions from 8a-hydroperoxy-α-tocopherone, the primary oxidation product of α-tocopherol by singlet oxygen. 相似文献
998.
The redox state of plastoquinone-pool in chloroplasts is crucial for driving many responses to variable environment, from short-term effects to those at the gene expression level. In the present studies, we showed for the first time that the plastoquinone-pool undergoes relatively fast oxidation during high light stress of low light-grown Arabidopsis plants. This oxidation was not caused by photoinhibition of photosystem II, but mainly by singlet oxygen generated in photosystem II and non-photochemical quenching in light harvesting complex antenna of the photosystem, as revealed in experiments with a singlet oxygen scavenger and with Arabidopsis npq4 mutant. The latter mechanism suppresses the influx of electrons to the plastoquinone-pool preventing its excessive reduction. The obtained results are of crucial importance in light of the function of the redox state of the plastoquinone-pool in triggering many high light-stimulated physiological responses of plants. 相似文献
999.
Waluk DP Sucharski F Sipos L Silberring J Hunt MC 《The Journal of biological chemistry》2012,287(20):16158-16167
Lysine acetylation is a major post-translational modification of proteins and regulates many physiological processes such as metabolism, cell migration, aging, and inflammation. Proteomic studies have identified numerous lysine-acetylated proteins in human and mouse models (Kim, S. C., Sprung, R., Chen, Y., Xu, Y., Ball, H., Pei, J., Cheng, T., Kho, Y., Xiao, H., Xiao, L., Grishin, N. V., White, M., Yang, X. J., and Zhao, Y. (2006) Mol. Cell 23, 607-618). One family of proteins identified in this study was the murine glycine N-acyltransferase (GLYAT) enzymes, which are acetylated on lysine 19. Lysine 19 is a conserved residue in human glycine N-acyltransferase-like 2 (hGLYATL2) and in several other species, showing that this residue may be important for enzyme function. Mutation of lysine 19 in recombinant hGLYATL2 to glutamine (K19Q) and arginine (K19R) resulted in a 50-80% lower production of N-oleoyl glycine and N-arachidonoylglycine, indicating that lysine 19 is important for enzyme function. LC/MS/MS confirmed that Lys-19 is not acetylated in wild-type hGLYATL2, indicating that Lys-19 requires to be deacetylated for full activity. The hGLYATL2 enzyme conjugates medium- and long-chain saturated and unsaturated acyl-CoA esters to glycine, resulting in the production of N-oleoyl glycine and also N-arachidonoyl glycine. N-Oleoyl glycine and N-arachidonoyl glycine are structurally and functionally related to endocannabinoids and have been identified as signaling molecules that regulate functions like the perception of pain and body temperature and also have anti-inflammatory properties. In conclusion, acetylation of lysine(s) in hGLYATL2 regulates the enzyme activity, thus linking post-translational modification of proteins with the production of biological signaling molecules, the N-acyl glycines. 相似文献
1000.
Plant genome modification by homologous recombination 总被引:11,自引:0,他引:11
The mechanisms and frequencies of various types of homologous recombination (HR) have been studied in plants for several years. However, the application of techniques involving HR for precise genome modification is still not routine. The low frequency of HR remains the major obstacle but recent progress in gene targeting in Arabidopsis and rice, as well as accumulating knowledge on the regulation of recombination levels, is an encouraging sign of the further development of HR-based approaches for genome engineering in plants. 相似文献