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Sparrman, Tobias
Publications (10 of 59) Show all publications
Dinh, V. M., Khokarale, S. G., Ojeda-May, P., Sparrman, T., Irgum, K. & Mikkola, J.-P. (2024). Ionic liquid strategy for chitosan production from chitin and molecular insights. RSC Sustainability, 2(4), 1154-1164
Open this publication in new window or tab >>Ionic liquid strategy for chitosan production from chitin and molecular insights
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2024 (English)In: RSC Sustainability, E-ISSN 2753-8125, Vol. 2, no 4, p. 1154-1164Article in journal (Refereed) Published
Abstract [en]

To produce chitosan is an interesting research. Chitosan is an important polysaccharide in terms of its various applications in industries and is produced from chitin, an abundant biopolymer in crustacean shell biomass wastes. Traditional processes for chitosan manufacture are commonly based on highly concentrated alkaline or acid solutions which are, however, severely eroding and harmful to the environment. In this study, we have described a ‘greener’ method using 1-ethyl-3-methylimidazolium acetate, [Emim][OAc] ionic liquid (IL), for decrystallization of shrimp crystalline chitin flakes followed by a microwave-mediated NaOH or tetrabutylammonium hydroxide, [TBA][OH], solution-based deacetylation for chitosan production. The decrease in crystallinity in IL pre-treated chitin was confirmed by XRD and SEM analysis which subsequently benefited chitosan production with up to 85% degree of deacetylation (%DDA) in shorter time periods (1-2 hours) and lower alkaline concentrations (20-40%). The %DDA in chitin/chitosan was estimated via FT-IR and NMR analysis. Notably, we could regenerate the ionic liquids: in case of [Emim][OAc] 97 wt.% and in case of [TBA][OH] 83 wt.% could be reused. Roles of ionic liquids in the process were discussed. Molecular dynamics (MD) simulations showed the roles of [TBA]+ cations in the molecular driving forces of [TBA][OH]-induced deacetylation mechanism. The strategy promises a sustainable and milder reaction approach to the existing highly corrosive alkaline- or acid-involved processes for chitosan production.

Place, publisher, year, edition, pages
Royal Society of Medicine Press, 2024
National Category
Chemical Sciences
Research subject
sustainability
Identifiers
urn:nbn:se:umu:diva-222314 (URN)10.1039/d4su00053f (DOI)2-s2.0-85189679118 (Scopus ID)
Available from: 2024-03-13 Created: 2024-03-13 Last updated: 2024-07-02Bibliographically approved
De Oliveira, D. H., Gowda, V., Sparrman, T., Gustafsson, L., Sanches Pires, R., Riekel, C., . . . Hedhammar, M. (2024). Structural conversion of the spidroin C-terminal domain during assembly of spider silk fibers. Nature Communications, 15(1), Article ID 4670.
Open this publication in new window or tab >>Structural conversion of the spidroin C-terminal domain during assembly of spider silk fibers
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2024 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 15, no 1, article id 4670Article in journal (Refereed) Published
Abstract [en]

The major ampullate Spidroin 1 (MaSp1) is the main protein of the dragline spider silk. The C-terminal (CT) domain of MaSp1 is crucial for the self-assembly into fibers but the details of how it contributes to the fiber formation remain unsolved. Here we exploit the fact that the CT domain can form silk-like fibers by itself to gain knowledge about this transition. Structural investigations of fibers from recombinantly produced CT domain from E. australis MaSp1 reveal an α-helix to β-sheet transition upon fiber formation and highlight the helix No4 segment as most likely to initiate the structural conversion. This prediction is corroborated by the finding that a peptide corresponding to helix No4 has the ability of pH-induced conversion into β-sheets and self-assembly into nanofibrils. Our results provide structural information about the CT domain in fiber form and clues about its role in triggering the structural conversion of spidroins during fiber assembly.

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-225959 (URN)10.1038/s41467-024-49111-5 (DOI)38821983 (PubMedID)2-s2.0-85195000928 (Scopus ID)
Available from: 2024-06-12 Created: 2024-06-12 Last updated: 2024-06-12Bibliographically approved
Clifton, L. A., Wacklin-Knecht, H. P., Ådén, J., Ul Mushtaq, A., Sparrman, T. & Gröbner, G. (2023). Creation of distinctive Bax-lipid complexes at mitochondrial membrane surfaces drives pore formation to initiate apoptosis. Paper presented at 2023/06/07. Science Advances, 9(22), Article ID eadg7940.
Open this publication in new window or tab >>Creation of distinctive Bax-lipid complexes at mitochondrial membrane surfaces drives pore formation to initiate apoptosis
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2023 (English)In: Science Advances, E-ISSN 2375-2548, Vol. 9, no 22, article id eadg7940Article in journal (Refereed) Published
Abstract [en]

Apotosis is an essential process tightly regulated by the Bcl-2 protein family where proapoptotic Bax triggers cell death by perforating the mitochondrial outer membrane. Although intensively studied, the molecular mechanism by which these proteins create apoptotic pores remains elusive. Here, we show that Bax creates pores by extracting lipids from outer mitochondrial membrane mimics by formation of Bax/lipid clusters that are deposited on the membrane surface. Time-resolved neutron reflectometry and Fourier transform infrared spectroscopy revealed two kinetically distinct phases in the pore formation process, both of which were critically dependent on cardiolipin levels. The initially fast adsorption of Bax on the mitochondrial membrane surface is followed by a slower formation of pores and Bax-lipid clusters on the membrane surface. Our findings provide a robust molecular understanding of mitochondrial membrane perforation by cell-killing Bax protein and illuminate the initial phases of programmed cellular death. Bax initiates apoptosis by perforating mitochondrial membranes via formation of pores and extramembranous Bax-lipid complexes.

Place, publisher, year, edition, pages
American Association for the Advancement of Science (AAAS), 2023
National Category
Biophysics
Identifiers
urn:nbn:se:umu:diva-209321 (URN)10.1126/sciadv.adg7940 (DOI)001009737900018 ()37267355 (PubMedID)2-s2.0-85160903390 (Scopus ID)
Conference
2023/06/07
Funder
Swedish Research Council, 2021-00167Swedish Research Council, 2016-06963The Kempe Foundations, JCK-132
Available from: 2023-06-08 Created: 2023-06-08 Last updated: 2023-09-05Bibliographically approved
Huynh, C. M., Mavliutova, L., Sparrman, T., Sellergren, B. & Irgum, K. (2023). Elucidation of the binding orientation in α2,3- and α2,6-linked neu5ac-gal epitopes toward a hydrophilic molecularly imprinted monolith. ACS Omega, 8(46), 44238-44249
Open this publication in new window or tab >>Elucidation of the binding orientation in α2,3- and α2,6-linked neu5ac-gal epitopes toward a hydrophilic molecularly imprinted monolith
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2023 (English)In: ACS Omega, E-ISSN 2470-1343, Vol. 8, no 46, p. 44238-44249Article in journal (Refereed) Published
Abstract [en]

N-Acetylneuraminic acid and its α2,3/α2,6-glycosidic linkages with galactose (Neu5Ac-Gal) are major carbohydrate antigen epitopes expressed in various pathological processes, such as cancer, influenza, and SARS-CoV-2. We here report a strategy for the synthesis and binding investigation of molecularly imprinted polymers (MIPs) toward α2,3 and α2,6 conformations of Neu5Ac-Gal antigens. Hydrophilic imprinted monoliths were synthesized from melamine monomer in the presence of four different templates, namely, N-acetylneuraminic acid (Neu5Ac), N-acetylneuraminic acid methyl ester (Neu5Ac-M), 3′-sialyllactose (3SL), and 6′-sialyllactose (6SL), in a tertiary solvent mixture at temperatures varying from −20 to +80 °C. The MIPs prepared at cryotemperatures showed a preferential affinity for the α2,6 linkage sequence of 6SL, with an imprinting factor of 2.21, whereas the α2,3 linkage sequence of 3SL resulted in nonspecific binding to the polymer scaffold. The preferable affinity for the α2,6 conformation of Neu5Ac-Gal was evident also when challenged by a mixture of other mono- and disaccharides in an aqueous test mixture. The use of saturation transfer difference nuclear magnetic resonance (STD-NMR) on suspensions of crushed monoliths allowed for directional interactions between the α2,3/α2,6 linkage sequences on their corresponding MIPs to be revealed. The Neu5Ac epitope, containing acetyl and polyalcohol moieties, was the major contributor to the sequence recognition for Neu5Ac(α2,6)Gal(β1,4)Glc, whereas contributions from the Gal and Glc segments were substantially lower.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2023
National Category
Organic Chemistry
Identifiers
urn:nbn:se:umu:diva-217983 (URN)10.1021/acsomega.3c06836 (DOI)38027366 (PubMedID)2-s2.0-85178321169 (Scopus ID)
Funder
EU, Horizon 2020, H2020EU, Horizon 2020, 722171
Available from: 2023-12-14 Created: 2023-12-14 Last updated: 2024-07-02Bibliographically approved
Clifton, L. A., Ul Mushtaq, A., Ådén, J., Sparrman, T., Wacklin-Knecht, H. & Gröbner, G. (2023). Insight into Bcl-2 proteins' functioning at mitochondrial membrane level. Biophysical Journal, 122(3S1), 232a-232a, Article ID 1130-Pos.
Open this publication in new window or tab >>Insight into Bcl-2 proteins' functioning at mitochondrial membrane level
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2023 (English)In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 122, no 3S1, p. 232a-232a, article id 1130-PosArticle in journal, Meeting abstract (Refereed) Published
Abstract [en]

Programmed cell death (apoptosis) is essential in life. In its intrinsic apoptotic pathway opposing members of the B-cell lymphoma 2 (Bcl-2) protein family control the permeability of the mitochondrial outer membrane (MOM) and the release of apoptotic factors such as cytochrome c. Any misregulation of this process can cause disorders most prominently cancer, where often upregulation of cell protecting (anti-apoptotic) Bcl-2 members such as the Bcl-2 membrane protein itself plays a notorious role by blocking MOM perforation by - often drug induced - apoptotic proteins such as Bax which would cause cancer cell death normally. Here, we apply neutron reflectometry (NR) on supported lipid bilayers which mimic MOM environment and solid state/liquid state NMR spectroscopy to unravel the molecular basis driving opposing proteins to interact with each other at the MOM; a mechanism which is not really understood yet due to lack of high-resolution structural insight. Based on our central hypothesis that Bcl-2 drives its cell-protecting function at a membrane-embedded location as revealed by NR (1), we focus i) to determine the structure of human Bcl-2 protein in its membrane setting by combining solution and solid-state NMR; ii) use NR to study the kinetics and lipid/protein pore assemblied upon binding of Bax to mitochondrial membranes and its membrane destroying activities there; and iii) unravel the nature of direct interaction between Bcl-2 and Bax to neutralize each other. Knowledge generated here, will be indispensable in understanding the regulative function of the Bcl-2 family at mitochondrial membranes.

Place, publisher, year, edition, pages
Elsevier, 2023
National Category
Biophysics
Identifiers
urn:nbn:se:umu:diva-205180 (URN)10.1016/j.bpj.2022.11.1366 (DOI)36783142 (PubMedID)2-s2.0-85148107754 (Scopus ID)
Available from: 2023-02-28 Created: 2023-02-28 Last updated: 2023-02-28Bibliographically approved
Verma, A., Åberg-Zingmark, E., Sparrman, T., Ul Mushtaq, A., Rogne, P., Grundström, C., . . . Wolf-Watz, M. (2022). Insights into the evolution of enzymatic specificity and catalysis: from Asgard archaea to human adenylate kinases [Letter to the editor]. Science Advances, 8(44), Article ID eabm4089.
Open this publication in new window or tab >>Insights into the evolution of enzymatic specificity and catalysis: from Asgard archaea to human adenylate kinases
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2022 (English)In: Science Advances, E-ISSN 2375-2548, Vol. 8, no 44, article id eabm4089Article in journal, Letter (Refereed) Published
Abstract [en]

Enzymatic catalysis is critically dependent on selectivity, active site architecture, and dynamics. To contribute insights into the interplay of these properties, we established an approach with NMR, crystallography, and MD simulations focused on the ubiquitous phosphotransferase adenylate kinase (AK) isolated from Odinarchaeota (OdinAK). Odinarchaeota belongs to the Asgard archaeal phylum that is believed to be the closest known ancestor to eukaryotes. We show that OdinAK is a hyperthermophilic trimer that, contrary to other AK family members, can use all NTPs for its phosphorylation reaction. Crystallographic structures of OdinAK-NTP complexes revealed a universal NTP-binding motif, while 19F NMR experiments uncovered a conserved and rate-limiting dynamic signature. As a consequence of trimerization, the active site of OdinAK was found to be lacking a critical catalytic residue and is therefore considered to be "atypical." On the basis of discovered relationships with human monomeric homologs, our findings are discussed in terms of evolution of enzymatic substrate specificity and cold adaptation.

Place, publisher, year, edition, pages
American Association for the Advancement of Science (AAAS), 2022
National Category
Biochemistry and Molecular Biology
Research subject
Biochemistry
Identifiers
urn:nbn:se:umu:diva-201106 (URN)10.1126/sciadv.abm4089 (DOI)000918406800003 ()36332013 (PubMedID)2-s2.0-85141889911 (Scopus ID)
Funder
Swedish Research Council, 2017-04203Swedish Research Council, 2019-03771Swedish Research Council, 2016-03599Knut and Alice Wallenberg Foundation, 2016-03599The Kempe Foundations, SMK-1869Carl Tryggers foundation , 17.504NIH (National Institutes of Health), (R01GM132481
Note

The Protein Expertise Platform (PEP) at the Umeå University is acknowledged for providing reagents for protein production, and M. Lindberg at PEP is appreciated for preparation of plasmids. We acknowledge MAX IV Laboratory (Lund, Sweden) for time on BioMAX and DESY (Hamburg, Germany) for time on PETRA-3. All NMR experiments were performed at the Swedish NMR Center at Umeå University. We also acknowledge the Swedish National Infrastructure for Computing (SNIC) at the High Performance Computing Center North (HPC2N) and the National Energy Research Scientific Computing Center (NERSC) for computational resources.

Available from: 2022-11-19 Created: 2022-11-19 Last updated: 2023-09-05Bibliographically approved
Hasegawa, S., Marshall, J., Sparrman, T. & Näsholm, T. (2021). Decadal nitrogen addition alters chemical composition of soil organic matter in a boreal forest. Geoderma, 386, Article ID 114906.
Open this publication in new window or tab >>Decadal nitrogen addition alters chemical composition of soil organic matter in a boreal forest
2021 (English)In: Geoderma, ISSN 0016-7061, E-ISSN 1872-6259, Vol. 386, article id 114906Article in journal (Refereed) Published
Abstract [en]

Boreal forests store approximately 470 Pg of carbon (C) in the soil, and rates of soil C accumulation are significantly enhanced by long-term nitrogen (N) enrichment. Dissecting the compositional profile of soils could help better understand the potential mechanisms driving changes in C cycling under enriched N conditions.

We examined the impacts of long-term N addition on the chemical composition of soil organic matter (SOM) in a mature boreal forest. Two large experimental plots (15 ha each) were established: a control and a fertilised plot. The latter received NH4NO3 fertilizer at an average rate of 75 kg N ha−1 year−1 for 12 years. While the centre of this plot received the prescribed amounts of fertilizer, the year-to-year variation in distribution of fertilizer around the designated edges of the plot created a gradient in N-loading. Along this gradient, a compositional shift in SOM in the organic horizon was assessed using two methods: pyrolysis-gas chromatography/mass spectrometry (GC/MS) and solid-state 13C nuclear magnetic resonance spectroscopy (13C NMR).

Both of these methods revealed that the chemical composition of SOM changed with increasing N loading, with an increased fraction of lignin derivatives (i.e., aromatic, methoxy/N-alkyl C) relative to that of carbohydrate (i.e., O-alkyl C), accompanied by increased soil C mass (kg m−2) at the fertilised plot. Also, the relative abundance of N compounds in the pyrolysis products increased with the N loading, mainly due to increased methyl N-acetyl-α-D-glucosaminide in the F/H horizon, plausibly of microbial origin. Microbial N processing likely contributed to soil accumulation of fertilizer-derived N.

Our results corroborate the hypothesis that addition of inorganic N suppresses enzymatic white-rot decomposition relative to non-enzymatic brown-rot oxidation. Taken together, our study suggests that N enrichment leads to a selective accumulation of lignin-derived compounds and points to a key role of such compounds for N-induced SOM accumulation.

Place, publisher, year, edition, pages
Elsevier, 2021
Keywords
Boreal forest, Carbon accumulation, Nitrogen enrichment, NMR, Pyrolysis, Soil organic matter
National Category
Soil Science Forest Science
Identifiers
urn:nbn:se:umu:diva-186319 (URN)10.1016/j.geoderma.2020.114906 (DOI)000613923000004 ()2-s2.0-85099139231 (Scopus ID)
Funder
Knut and Alice Wallenberg Foundation, 2015.0047The Kempe Foundations
Available from: 2021-07-21 Created: 2021-07-21 Last updated: 2021-07-21Bibliographically approved
Ul Mushtaq, A., Ådén, J., Sparrman, T., Hedenström, M. & Gröbner, G. (2021). Insight into Functional Membrane Proteins by Solution NMR: The Human Bcl-2 Protein - A Promising Cancer Drug Target. Molecules, 26(5), Article ID 1467.
Open this publication in new window or tab >>Insight into Functional Membrane Proteins by Solution NMR: The Human Bcl-2 Protein - A Promising Cancer Drug Target
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2021 (English)In: Molecules, ISSN 1431-5157, E-ISSN 1420-3049, Vol. 26, no 5, article id 1467Article in journal (Refereed) Published
Abstract [en]

Evasion from programmed cell death (apoptosis) is the main hallmark of cancer and a major cause of resistance to therapy. Many tumors simply ensure survival by over-expressing the cell-protecting (anti-apoptotic) Bcl-2 membrane protein involved in apoptotic regulation. However, the molecular mechanism by which Bcl-2 protein in its mitochondrial outer membrane location protects cells remains elusive due to the absence of structural insight; and current strategies to therapeutically interfere with these Bcl-2 sensitive cancers are limited. Here, we present an NMR-based approach to enable structural insight into Bcl-2 function; an approach also ideal as a fragment-based drug discovery platform for further identification and development of promising molecular Bcl-2 inhibitors. By using solution NMR spectroscopy on fully functional intact human Bcl-2 protein in a membrane-mimicking micellar environment, and constructs with specific functions remaining, we present a strategy for structure determination and specific drug screening of functional subunits of the Bcl-2 protein as targets. Using 19F NMR and a specific fragment library (Bionet) with fluorinated compounds we can successfully identify various binders and validate our strategy in the hunt for novel Bcl-2 selective cancer drug strategies to treat currently incurable Bcl-2 sensitive tumors.

Place, publisher, year, edition, pages
MDPI, 2021
Keywords
Bcl-2 membrane protein, NMR, drug screening
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-181526 (URN)10.3390/molecules26051467 (DOI)000628449100001 ()2-s2.0-85103920124 (Scopus ID)
Funder
Swedish Research Council, 2016-06963Swedish Cancer Society, CAN 2015/482The Kempe FoundationsKnut and Alice Wallenberg Foundation
Available from: 2021-03-17 Created: 2021-03-17 Last updated: 2023-09-05Bibliographically approved
Ul Mushtaq, A., Ådén, J., Clifton, L. A., Wacklin-Knecht, H., Campana, M., Dingeldein, A. P. G., . . . Gröbner, G. (2021). Neutron reflectometry and NMR spectroscopy of full-length Bcl-2 protein reveal its membrane localization and conformation. Communications Biology, 4(1), Article ID 507.
Open this publication in new window or tab >>Neutron reflectometry and NMR spectroscopy of full-length Bcl-2 protein reveal its membrane localization and conformation
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2021 (English)In: Communications Biology, E-ISSN 2399-3642, Vol. 4, no 1, article id 507Article in journal (Refereed) Published
Abstract [en]

B-cell lymphoma 2 (Bcl-2) proteins are the main regulators of mitochondrial apoptosis. Anti-apoptotic Bcl-2 proteins possess a hydrophobic tail-anchor enabling them to translocate to their target membrane and to shift into an active conformation where they inhibit pro-apoptotic Bcl-2 proteins to ensure cell survival. To address the unknown molecular basis of their cell-protecting functionality, we used intact human Bcl-2 protein natively residing at the mitochondrial outer membrane and applied neutron reflectometry and NMR spectroscopy. Here we show that the active full-length protein is entirely buried into its target membrane except for the regulatory flexible loop domain (FLD), which stretches into the aqueous exterior. The membrane location of Bcl-2 and its conformational state seems to be important for its cell-protecting activity, often infamously upregulated in cancers. Most likely, this situation enables the Bcl-2 protein to sequester pro-apoptotic Bcl-2 proteins at the membrane level while sensing cytosolic regulative signals via its FLD region.

Place, publisher, year, edition, pages
Springer Nature, 2021
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-182710 (URN)10.1038/s42003-021-02032-1 (DOI)000647062000003 ()2-s2.0-85105112344 (Scopus ID)
Funder
Swedish Research CouncilSwedish Cancer SocietyThe Kempe FoundationsKnut and Alice Wallenberg Foundation
Available from: 2021-05-04 Created: 2021-05-04 Last updated: 2023-09-05Bibliographically approved
Shamshir, A., Sparrman, T. & Westlund, P.-O. (2020). Analysis of the behaviour of confined molecules using 2H T1 nuclear magnetic relaxation dispersion. Molecular Physics, 118(6), Article ID e1645367.
Open this publication in new window or tab >>Analysis of the behaviour of confined molecules using 2H T1 nuclear magnetic relaxation dispersion
2020 (English)In: Molecular Physics, ISSN 0026-8976, E-ISSN 1362-3028, Vol. 118, no 6, article id e1645367Article in journal (Refereed) Published
Abstract [en]

A four-site exchange model is developed in order to explain deuterium -nuclear magnetic relaxation dispersion (NMRD) profiles of acetonitrile in silica pore systems. The four-site exchange model comprises a bulk, surface and two types of burried or cavity sites. It is found that the residence time of acetonitrile- at a flat Si-surface is less than 100 ps. No bilayer-like ordering of acetonitrile is formed at the Si-surface because no quadrupole splitting was observed. The dispersion in the deuterium T1-NMRD profiles are due to relatively few so-called beta-sites with molecular residence time in the range 0.2-2 micro seconds. This deuterium T-NMR dispersion experiment suggest that the retention time of different analysts can be studied in terms of their residence time in beta sites.

Place, publisher, year, edition, pages
Taylor & Francis, 2020
Keywords
Spin-lattice relaxation time of acetonitrile-d3, NMRD, molecular origin of the retention time, 4-site exchange model
National Category
Physical Chemistry
Identifiers
urn:nbn:se:umu:diva-162676 (URN)10.1080/00268976.2019.1645367 (DOI)000479433000001 ()2-s2.0-85083909827 (Scopus ID)
Available from: 2019-09-02 Created: 2019-09-02 Last updated: 2023-03-23Bibliographically approved
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