| 1. |
- Hansson Wahlberg, Tobias, et al.
(författare)
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Are there any Institutional Facts?
- 2019
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Ingår i: Maurinian Truths : Essays in Honour of Anna-Sofia Maurin on her 50th Birthday - Essays in Honour of Anna-Sofia Maurin on her 50th Birthday. - 9789188899538 - 9789188899545 ; , s. 83-88
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Ekenberg, Love, et al.
(författare)
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Deliberation, representation, equity : research approaches, tools and algorithms for participatory processes
- 2017
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- What can we learn about the development of public interaction in e-democracy from a drama delivered by mobile headphones to an audience standing around a shopping center in a Stockholm suburb? In democratic societies there is widespread acknowledgment of the need to incorporate citizens' input in decision-making processes in more or less structured ways. But participatory decision making is balancing on the borders of inclusion, structure, precision and accuracy. To simply enable more participation will not yield enhanced democracy, and there is a clear need for more elaborated elicitation and decision analytical tools. This rigorous and thought-provoking volume draws on a stimulating variety of international case studies, from flood risk management in the Red River Delta of Vietnam, to the consideration of alternatives to gold mining in Ro?ia Montana in Transylvania, to the application of multi-criteria decision analysis in evaluating the impact of e-learning opportunities at Uganda's Makerere University. Editors Love Ekenberg (senior research scholar, International Institute for Applied Systems Analysis [IIASA], Laxenburg, professor of Computer and Systems Sciences, Stockholm University), Karin Hansson (artist and research fellow, Department of Computer and Systems Sciences, Stockholm University), Mats Danielson (vice president and professor of Computer and Systems Sciences, Stockholm University, affiliate researcher, IIASA) and Göran Cars (professor of Societal Planning and Environment, Royal Institute of Technology, Stockholm) draw innovative collaborations between mathematics, social science, and the arts. They develop new problem formulations and solutions, with the aim of carrying decisions from agenda setting and problem awareness through to feasible courses of action by setting objectives, alternative generation, consequence assessments, and trade-off clarifications. As a result, this book is important new reading for decision makers in government, public administration and urban planning, as well as students and researchers in the fields of participatory democracy, urban planning, social policy, communication design, participatory art, decision theory, risk analysis and computer and systems sciences.
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| 3. |
- Hansson, Mattias, et al.
(författare)
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Amino acid residues His183 and Glu264 in Bacillus subtilis ferrochelatase direct and facilitate the insertion of metal ion into protoporphyrin IX
- 2007
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 46:1, s. 87-94
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Tidskriftsartikel (refereegranskat)abstract
- Ferrochelatase catalyzes the terminal step in the heme biosynthetic pathway, i.e., the incorporation of Fe(II) into protoporphyrin IX. Various biochemical and biophysical methods have been used to probe the enzyme for metal binding residues and the location of the active site. However, the location of the metal binding site and the path of the metal into the porphyrin are still disputed. Using site-directed mutagenesis on Bacillus subtilis ferrochelatase we demonstrate that exchange of the conserved residues His183 and Glu264 affects the metal affinity of the enzyme. We also present the first X-ray crystal structure of ferrochelatase with iron. Only a single iron was found in the active site, coordinated in a square pyramidal fashion by two amino acid residues, His183 and Glu264, and three water molecules. This iron was not present in the structure of a His183Ala modified ferrochelatase. The results strongly suggest that the insertion of a metal ion into protoporphyrin IX by ferrochelatase occurs from a metal binding site represented by His183 and Glu264.
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| 4. |
- Hansson, Mattias, et al.
(författare)
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Bacterial ferrochelatase turns human: Tyr13 determines the apparent metal specificity of Bacillus subtilis ferrochelatase.
- 2011
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Ingår i: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 1432-1327 .- 0949-8257. ; 16:2, s. 235-242
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Tidskriftsartikel (refereegranskat)abstract
- Ferrochelatase catalyzes the insertion of Fe(2+) into protoporphyrin IX. The enzymatic product heme (protoheme IX) is a well-known cofactor in a wide range of proteins. The insertion of metal ions other than Fe(2+) occurs rarely in vivo, but all ferrochelatases that have been studied can insert Zn(2+) at a good rate in vitro. Co(2+), but not Cu(2+), is known to be a good substrate of the mammalian and Saccharomyces cerevisiae ferrochelatases. In contrast, Cu(2+), but not Co(2+), has been found to be a good substrate of bacterial Bacillus subtilis ferrochelatase. It is not known how ferrochelatase discriminates between different metal ion substrates. Structural analysis of B. subtilis ferrochelatase has shown that Tyr13 is an indirect ligand of Fe(2+) and a direct ligand of a copper mesoporphyrin product. A structure-based comparison revealed that Tyr13 aligns with a Met residue in the S. cerevisiae and human ferrochelatases. Tyr13 was changed to Met in the B. subtilis enzyme by site-directed mutagenesis. Enzymatic measurements showed that the modified enzyme inserted Co(2+) at a higher rate than the wild-type B. subtilis ferrochelatase, but it had lost the ability to use Cu(2+) as a substrate. Thus, the B. subtilis Tyr13Met ferrochelatase showed the same metal specificity as that of the ferrochelatases from S. cerevisiae and human.
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| 5. |
- Karlberg, Tobias, et al.
(författare)
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Porphyrin Binding and Distortion and Substrate Specificity in the Ferrochelatase Reaction: The Role of Active Site Residues.
- 2008
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 378:5, s. 1074-1083
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Tidskriftsartikel (refereegranskat)abstract
- The specific insertion of a divalent metal ion into tetrapyrrole macrocycles is catalyzed by a group of enzymes called chelatases. Distortion of the tetrapyrrole has been proposed to be an important component of the mechanism of metallation. We present the structures of two different inhibitor complexes: (1) N-methylmesoporphyrin (N-MeMP) with the His183Ala variant of Bacillus subtilis ferrochelatase; (2) the wild-type form of the same enzyme with deuteroporphyrin IX 2,4-disulfonic acid dihydrochloride (dSDP). Analysis of the structures showed that only one N-MeMP isomer out of the eight possible was bound to the protein and it was different from the isomer that was earlier found to bind to the wild-type enzyme. A comparison of the distortion of this porphyrin with other porphyrin complexes of ferrochelatase and a catalytic antibody with ferrochelatase activity using normal-coordinate structural decomposition reveals that certain types of distortion are predominant in all these complexes. On the other hand, dSDP, which binds closer to the protein surface compared to N-MeMP, does not undergo any distortion upon binding to the protein, underscoring that the position of the porphyrin within the active site pocket is crucial for generating the distortion required for metal insertion. In addition, in contrast to the wild-type enzyme, Cu(2+)-soaking of the His183Ala variant complex did not show any traces of porphyrin metallation. Collectively, these results provide new insights into the role of the active site residues of ferrochelatase in controlling stereospecificity, distortion and metallation.
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| 6. |
- Shipovskov, Stepan, et al.
(författare)
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Metallation of the transition-state inhibitor N-methyl mesoporphyrin by ferrochelatase: Implications for the catalytic reaction mechanism
- 2005
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 352:5, s. 1081-1090
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Tidskriftsartikel (refereegranskat)abstract
- Insertion of metals into various tetrapyrroles is catalysed by a group of enzymes called chelatases, e.g. nickel, cobalt, magnesium and ferrochelatase. It has been proposed that catalytic metallation includes distorting the porphyrin substrate by the enzyme towards a transition state-like geometry in which at least one of the pyrrole rings will be available for metal chelation. Here, we present a study of metal insertion into the transition-state inhibitor of protoporphyrin IX ferrochelatase, N-methyl mesoporphyrin (N-MeMP), by time-resolved crystallography and mass spectrometry with and without the presence of ferrochelatase. The results show that metallation of N-MeMP has a very limited effect on the conformation of the residues that participate in porphyrin and metal binding. These findings support theoretical data, which indicate that product release is controlled largely by the strain created by metal insertion into the distorted porphyrin. The results suggest that, similar to noncatalytic metallation of N-MeMP, the ferrochelatase-assisted metallation depends on the ligand exchange rate for the respective metal. Moreover, ferrochelatase catalyses insertion of Cu(II) and Zn(II) into N-MeMP with a rate that is about 20 times faster than non-enzymatic metallation in solution, suggesting that the catalytic strategy of ferrochelatase includes a stage of acceleration of the rate of ligand exchange for the metal substrate. The greater efficiency of N-MeMP metallation by Cu(II), as compared to Zn(II), contrasts with the Km values for Zn(II), (17 mu M) and Cu(II) (170 mu M) obtained for metallation of protoporphyrin IX. We suggest that this difference in metal specificity depends on the type of distortion imposed by the enzyme on protoporphyrin IX, which is different from the intrinsic non-planar distortion of N-MeMP. A mechanism of control of metal specificity by porphyrin distortion may be general for different chelatases, and may have common features with the mechanism of metal specificity in crown ethers.(c) 2005 Elsevier Ltd. All rights reserved.
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| 7. |
- Skillbäck, Tobias, et al.
(författare)
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A novel quantification-driven proteomic strategy identifies an endogenous peptide of pleiotrophin as a new biomarker of Alzheimer's disease
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- We present a new, quantification-driven proteomic approach to identifying biomarkers. In contrast to the identification-driven approach, limited in scope to peptides that are identified by database searching in the first step, all MS data are considered to select biomarker candidates. The endopeptidome of cerebrospinal fluid from 40 Alzheimer's disease (AD) patients, 40 subjects with mild cognitive impairment, and 40 controls with subjective cognitive decline was analyzed using multiplex isobaric labeling. Spectral clustering was used to match MS/MS spectra. The top biomarker candidate cluster (215% higher in AD compared to controls, area under ROC curve = 0.96) was identified as a fragment of pleiotrophin located near the protein's C-terminus. Analysis of another cohort (n = 60 over four clinical groups) verified that the biomarker was increased in AD patients while no change in controls, Parkinson's disease or progressive supranuclear palsy was observed. The identification of the novel biomarker pleiotrophin 151-166 demonstrates that our quantification-driven proteomic approach is a promising method for biomarker discovery, which may be universally applicable in clinical proteomics.
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