| 1. |
- Baykal, Abdulhadi, et al.
(författare)
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Synthesis and Characterization of High Catalytic Activity Magnetic Fe3O4 Supported Pd Nanocatalyst
- 2013
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Ingår i: Journal of Superconductivity and Novel Magnetism. - : Springer Science and Business Media LLC. - 1557-1939 .- 1557-1947. ; 26:1, s. 165-171
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Tidskriftsartikel (refereegranskat)abstract
- This study reports the fabrication and characterization of magnetically recyclable catalysts of Fe3O4-Pd nanocomposite as highly effective catalysts for reduction reactions in liquid phase. The characterization of Fe3O4-Pd MRCs were done by X-ray powder diffraction, A +/- nfrared spectroscopy, thermal analyzer, transmission electron spectroscopy, A +/- nductively coupled plasma, UV-Vis spectroscopy, vibrating sample magnetometer, respectively. The reduction of Pd2+ was accomplished with polyethylene glycol 400 (PEG-400) and Fe3O4 nanoparticles were prepared by co-precipitation of FeCI(3)a <...6H(2)O and FeCl(2)a <...4H(2)O. Thus formed Fe3O4-Pd MRCs showed a very high activity in reduction reactions of 4-nitro-aniline and 1,3-di-nitrobenzene in liquid phase. Magnetic character of this system allowed recovery and multiple use without significant loss of its catalytic activity.
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| 2. |
- Helgstrand, Charlotte, et al.
(författare)
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A Leukotriene A(4) Hydrolase-Related Aminopeptidase from Yeast Undergoes Induced Fit upon Inhibitor Binding.
- 2011
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 406, s. 120-134
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Tidskriftsartikel (refereegranskat)abstract
- Vertebrate leukotriene A(4) hydrolases are bifunctional zinc metalloenzymes with an epoxide hydrolase and an aminopeptidase activity. In contrast, highly homologous enzymes from lower organisms only have the aminopeptidase activity. From sequence comparisons, it is not clear why this difference occurs. In order to obtain more information on the evolutionary relationship between these enzymes and their activities, the structure of a closely related leucine aminopeptidase from Saccharomyces cerevisiae that only shows a very low epoxide hydrolase activity was determined. To investigate the molecular architecture of the active site, the structures of both the native protein and the protein in complex with the aminopeptidase inhibitor bestatin were solved. These structures show a more spacious active site, and the protected cavity in which the labile substrate leukotriene A(4) is bound in the human enzyme is partially obstructed and in other parts is more solvent accessible. Furthermore, the enzyme undergoes induced fit upon binding of the inhibitor bestatin, leading to a movement of the C-terminal domain. The main triggers for the domain movement are a conformational change of Tyr312 and a subtle change in backbone conformation of the PYGAMEN fingerprint region for peptide substrate recognition. This leads to a change in the hydrogen-bonding network pulling the C-terminal domain into a different position. Inasmuch as bestatin is a structural analogue of a leucyl dipeptide and may be regarded as a transition state mimic, our results imply that the enzyme undergoes induced fit during substrate binding and turnover.
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| 3. |
- Lindh, Ingrid, et al.
(författare)
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Type II collagen antibody response is enriched in the synovial fluid of rheumatoid joints and directed to the same major epitopes as in collagen induced arthritis in primates and mice
- 2014
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Ingår i: Arthritis Research & Therapy. - London : BioMed Central (BMC). - 1478-6362 .- 1478-6354. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Antibodies towards type II collagen (CII) are detected in patients with rheumatoid arthritis (RA) and in non-human primates and rodents with collagen induced arthritis (CIA). We have previously shown that antibodies specific for several CII-epitopes are pathogenic using monoclonal antibodies from arthritic mice, although the role of different anti-CII epitopes has not been investigated in detail in other species. We therefore performed an inter-species comparative study of the autoantibody response to CII in patients with RA versus monkeys and mice with CIA. METHODS: Analysis of the full epitope repertoire along the disease course of CIA was performed using a library of CII triple-helical peptides. The antibody responses to the major CII epitopes were analyzed in sera and synovial fluid from RA patients, and in sera from rhesus monkeys (Macaca mulatta), common marmosets (Callithrix jacchus) and mice. RESULTS: Many CII epitopes including the major C1, U1, and J1 were associated with established CIA and arginine residues played an important role in the anti-CII antibody interactions. The major epitopes were also recognized in RA patients, both in sera and even more pronounced in synovial fluid: 77% of the patients had antibodies to the U1 epitope. The anti-CII immune response was not restricted to the anti-citrulline protein antibodies (ACPA) positive RA group. CONCLUSION: CII conformational dependent antibody responses are common in RA and are likely to originate from rheumatoid joints but did not show a correlation with ACPA response. Importantly, the fine specificity of the anti-CII response is similar with CIA in monkeys and rodents where the recognized epitopes are conserved and have a major pathogenic role. Thus, anti-CII antibodies may both contribute to, as well as be the consequence of, local joint inflammation. © 2014 Lindh et al.; licensee BioMed Central Ltd.
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| 4. |
- Nurmemmedov, Elmar, et al.
(författare)
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New insights into DNA-binding behavior of Wilms tumor protein (WT1)--a dual study.
- 2009
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Ingår i: Biophysical Chemistry. - : Elsevier BV. - 1873-4200 .- 0301-4622. ; 145:2-3, s. 116-125
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Tidskriftsartikel (refereegranskat)abstract
- Wilms Tumor suppressor protein (WT1) is a transcription factor that is involved in a variety of developmental functions during organ development. It is also implicated in the pathology of several different cancer forms. The protein contains four C(2)H(2)-type zinc fingers and it specifically binds GC-rich sequences in the promoter regions of its target genes, which are either up or down regulated. Two properties make WT1 a more unusual transcription factor - an unconventional amino acid composition for zinc finger 1, and the insertion of a tri-peptide KTS in some of the splice isoforms of WT1. Using six WT1 constructs in which zinc fingers are systematically deleted, a dual study based on a bacterial 1-hybrid system and surface plasmon resonance measurements is performed. The experiments show that the effect of zinc finger 1 is not significant in terms of overall DNA-binding kinetics, however it influences both the specificity of target recognition and stability of interaction in presence of KTS. The KTS insertion, however, only mildly retards binding affinity, mainly by affecting the on-rate. We suggest that the insertion disturbs zinc finger 4 from its binding frame, thus weakening the rate of target recognition. Finally, for the construct in which both zinc fingers 1 and 4 were deleted, the two middle fingers 2-3 still could function as a 'minimal DNA-recognition domain' for WT1, however the formation of a stable protein-DNA complex is impaired since the overall affinity was dramatically reduced mainly since the off-rate was severely affected.
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| 5. |
- Uysal, Hüseyin, et al.
(författare)
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Antibodies to citrullinated proteins : molecular interactions and arthritogenicity
- 2010
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Ingår i: Immunological Reviews. - Hoboken, NJ : Wiley-Blackwell Publishing Inc.. - 0105-2896 .- 1600-065X. ; 233:1, s. 9-33
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of antibodies specific for citrullinated protein epitopes [anti-citrullinated protein antibodies (ACPAs)] is a hallmark for the diagnosis and prognosis of rheumatoid arthritis (RA) and will also be a useful tool for understanding the fundamental pathologic processes. There are several essential questions pertaining to ACPA that remain to be explored, such as understanding the early specificity of the underlying T-cell recognition, whether the production of ACPA is a primary or secondary process, and in the event of such antibodies being arthritogenic, whether they could possibly regulate the disease development. To answer these questions, animal models are needed, but unfortunately ACPA is not a prominent feature of any of the classical animal models of RA. However, we showed recently that ACPA can be isolated from animals susceptible to collagen-induced arthritis that are specific for citrullinated type II collagen (CII). The citrulline specificity could be visualized, and the specificity is determined primarily by a direct interaction with citrulline. We also demonstrated that these antibodies are specific for the citrullinated epitopes and are pathogenic in vivo. A new hypothesis to explain how inflammation in RA can be directed to cartilaginous joints and be self-perpetuating is suggested, which involves recognition of post-translational modifications (glycosylation and citrullination) on CII by T and B cells that can have both arthritogenic and regulatory consequences. © 2009 John Wiley & Sons A/S.
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| 6. |
- Uysal, Hüseyin
(författare)
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Structural and Functional Studies on Posttranslational Modifications of Collagen type II in Rheumatoid Arthritis.
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The molecular mechanisms behind the development and progression of rheumatoid arthritis are not known in fine details. Both humoral and cellular responses against collagen type II in joint cartilage seems to be important for the disease development. Especially posttranslational modifications on collagen type II are important in regulation of molecular mechanisms implicated in the disease. In this thesis we tried to identify molecular principles of anti-collagen immunity and its relation with pathogenicity by mainly X-ray crystallography. The crystal structure of anti-collagen antibody CIIC1 showed that it not only binds to collagen type II but also cross reacts with other immunoglobulins which is the typical behavior of rheumatoid factors. The arthritogenic and collagen specific antibody CIIC1 with this dual behavior suggests that RFs specific for joint proteins may form large immune complexes in the joints and simultaneously trigger inflammation and create a vicious cycle that produces new RFs in the way to a complete RA. The second article from the thesis describes the recognition of a citrullinated peptide from collagen type II by the arthritis enhancing antibody ACC4. The structure provides important clues explaining the higher antigenicity of the citrullinated peptide therefore the high titer of the ACPA antibodies in RA. In addition, we also showed that the citrullinated CII epitopes recognized by ACC4 and other ACC antibodies exist on the inflamed cartilage and in the synovial fluid which suggests that ACPA antibodies play a role in a vicious cycle that keeps inflammation continuing. Inflammation causes the formation of citrullinated antigenic epitopes or peptides which drives the formation of new ACPA antibodies eventually paves the way to a chronic inflammation and RA. The last two papers describe our experimental design to understand the role of cellular response against collagen type II and against another posttranslational modification which is glycosylation on collagen type II. In this context, we reported, in paper III, the experimental procedure that resulted in successful crystallization of MHC class II Aq presenting immunodominant CII peptide. In paper IV, experimental design for efficient production of Aq restricted collagen specific T cell receptors HCQ3 and HCR2 in insect cells by fusing to leucine zippers were described.
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| 7. |
- Uysal, Hüseyin, et al.
(författare)
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Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis
- 2009
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Ingår i: Journal of Experimental Medicine. - New York, NY : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 206:2, s. 449-462
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Tidskriftsartikel (refereegranskat)abstract
- Antibodies to citrulline-modified proteins have a high diagnostic value in rheumatoid arthritis (RA). However, their biological role in disease development is still unclear. To obtain insight into this question, a panel of mouse monoclonal antibodies was generated against a major triple helical collagen type II (CII) epitope (position 359-369; ARGLTGRPGDA) with or without arginines modified by citrullination. These antibodies bind cartilage and synovial tissue, and mediate arthritis in mice. Detection of citrullinated CII from RA patients' synovial fluid demonstrates that cartilage-derived CII is indeed citrullinated in vivo. The structure determination of a Fab fragment of one of these antibodies in complex with a citrullinated peptide showed a surprising beta-turn conformation of the peptide and provided information on citrulline recognition. Based on these findings, we propose that autoimmunity to CII, leading to the production of antibodies specific for both native and citrullinated CII, is an important pathogenic factor in the development of RA.
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| 8. |
- Uysal, Hüseyin, et al.
(författare)
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The crystal structure of the pathogenic collagen type II-specific mouse monoclonal antibody CIIC1 Fab : Structure to function analysis
- 2008
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Ingår i: Molecular Immunology. - Oxford : Elsevier. - 0161-5890 .- 1872-9142. ; 45:8, s. 2196-2204
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Tidskriftsartikel (refereegranskat)abstract
- Monoclonal anti-collagen type II antibody CIIC1 is an arthritogenic autoantibody, which induces arthritis in mice. We crystallized and solved the structure of CIIC1 Fab molecule. Analysis of structure revealed an interaction between the CDR regions of one Fab to the CH1 domain of another Fab, which resembles an antibody-antigen interaction. ELISA experiments confirmed the cross-reactivity of both the full CIIC1 antibody and a single chain Fv fragment to other anti-collagen antibodies which are of different isotypes and epitope specificity. The rheumatoid factor like reactivity of CIIC1 antibody together with its collagen type II specificity may explain the pathogenicity of this antibody. © 2007 Elsevier Ltd. All rights reserved.
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