{"entity": "journal", "iuid": "9bcd66cc59a644e0942d2b169e9e2dc0", "timestamp": "2026-07-17T08:22:49.545Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/RSC%20Chem%20Biol.json"}, "display": {"href": "https://publications.scilifelab.se/journal/RSC%20Chem%20Biol"}}, "title": "RSC Chem Biol", "issn": "2633-0679", "issn-l": null, "publications_count": 6, "publications": [{"entity": "publication", "iuid": "c3cc39df288e4158b74d51e4eceda6bc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c3cc39df288e4158b74d51e4eceda6bc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c3cc39df288e4158b74d51e4eceda6bc"}}, "title": "High-resolution structure of proIAPP(1-48) fibrils suggests a mechanistic pathway for diabetes-associated IAPP fibril polymorphs.", "authors": [{"family": "Valli", "given": "Dylan", "initials": "D", "orcid": "0009-0005-6060-4169", "researcher": {"href": "https://publications.scilifelab.se/researcher/56aa1f7e1c77487a95cbe1070944dd3c.json"}}, {"family": "Maj", "given": "Micha\u0142", "initials": "M", "orcid": "0000-0003-1567-9514", "researcher": {"href": "https://publications.scilifelab.se/researcher/1be0f07d0c5f40adac62cf38f2244e79.json"}}], "type": "journal article", "published": "2025-10-31", "journal": {"title": "RSC Chem Biol", "issn": "2633-0679", "issn-l": null}, "abstract": "The human islet amyloid polypeptide (hIAPP) aggregates into amyloid fibrils that contribute to \u03b2-cell failure in type 2 diabetes. hIAPP is produced from a 67-residue precursor, proIAPP, but incomplete cleavage by prohormone convertase 2 (PC2) produces the 48-residue intermediate proIAPP(1-48), which accelerates amyloid formation in vivo. Here we show that proIAPP(1-48) assembles almost exclusively into a single fibril polymorph. Using cryo-electron microscopy we solved its structure at 3.5 \u00c5 resolution and uncovered a P-shaped, C2-symmetric dimer whose backbone and side-chain packing are nearly identical to the disease-associated TW2 polymorph propagated from pancreatic tissue, although with different helical symmetry. All eleven extra N-terminal residues remain disordered but create a weak density around His29. Based on time-averaged density derived from molecular dynamics (MD) simulations, we identified multiple hydrogen(H)-bonding interactions, which may contribute to stabilising the TW2-like fold and explain the peripheral cryo-EM density. These data establish a structural link between defective proIAPP processing and the polymorphic spectrum of islet amyloid and suggest a seeding pathway by which proIAPP(1-48) templates pathogenic architectures that fully processed hIAPP rarely adopts in vitro.", "doi": "10.1039/d5cb00228a", "pmid": "41210656", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12590159"}, {"db": "pii", "key": "d5cb00228a"}], "notes": [], "created": "2025-11-24T16:00:26.102Z", "modified": "2025-11-24T16:00:26.208Z"}, {"entity": "publication", "iuid": "ea1d7c59296941b4bb2c44e61fe0cac6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ea1d7c59296941b4bb2c44e61fe0cac6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ea1d7c59296941b4bb2c44e61fe0cac6"}}, "title": "Nucleobase catalysts for the enzymatic activation of 8-oxoguanine DNA glycosylase 1.", "authors": [{"family": "Hank", "given": "Emily C", "initials": "EC", "orcid": "0000-0002-3777-4697", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3e38aa74d2c4ae0b7c77d7f1da17727.json"}}, {"family": "D'Arcy-Evans", "given": "Nicholas D", "initials": "ND"}, {"family": "Scaletti", "given": "Emma Rose", "initials": "ER"}, {"family": "Ben\u00edtez-Buelga", "given": "Carlos", "initials": "C"}, {"family": "Wallner", "given": "Olov", "initials": "O", "orcid": "0000-0002-6481-237X", "researcher": {"href": "https://publications.scilifelab.se/researcher/83eb2f7ee2f34f2cbacaae2dadcd90e9.json"}}, {"family": "Ortis", "given": "Florian", "initials": "F"}, {"family": "Zhou", "given": "Kaixin", "initials": "K"}, {"family": "Meng", "given": "Liuzhen", "initials": "L"}, {"family": "Del Prado", "given": "Alicia", "initials": "A", "orcid": "0000-0002-5480-0367", "researcher": {"href": "https://publications.scilifelab.se/researcher/39389cbfdeac46e8985c1597e00d45e1.json"}}, {"family": "Calvo", "given": "Patricia", "initials": "P"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "Nierlin", "given": "Karen", "initials": "K"}, {"family": "Ko\u0161enina", "given": "Sara", "initials": "S", "orcid": "0000-0001-7893-0249", "researcher": {"href": "https://publications.scilifelab.se/researcher/9370d4ecf19c438bb205c43c23f94f26.json"}}, {"family": "Kr\u00e4mer", "given": "Andreas", "initials": "A"}, {"family": "Eddershaw", "given": "Alice", "initials": "A"}, {"family": "Kehler", "given": "Mario", "initials": "M"}, {"family": "Long", "given": "Maeve", "initials": "M", "orcid": "0000-0001-5146-0750", "researcher": {"href": "https://publications.scilifelab.se/researcher/b68df86f81504376b77b98b0916c84c4.json"}}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd07c6c543544af1a904e039f73ba857.json"}}, {"family": "Dawson", "given": "Holly", "initials": "H"}, {"family": "Stewart", "given": "Josephine", "initials": "J", "orcid": "0000-0002-3506-5264", "researcher": {"href": "https://publications.scilifelab.se/researcher/62e8f2e54f1a4f1d96d8f4ae1de97a93.json"}}, {"family": "Dickey", "given": "Adam", "initials": "A"}, {"family": "Astorga", "given": "Mikhael E", "initials": "ME"}, {"family": "Varga", "given": "Marek", "initials": "M"}, {"family": "Homan", "given": "Evert J", "initials": "EJ", "orcid": "0000-0002-9057-1848", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0d6d2714b2544bfa37d383ef1357ba4.json"}}, {"family": "Scobie", "given": "Martin", "initials": "M", "orcid": "0000-0002-7073-8495", "researcher": {"href": "https://publications.scilifelab.se/researcher/87c041a8b3414f5db02873dc8013806b.json"}}, {"family": "Knapp", "given": "Stefan", "initials": "S", "orcid": "0000-0001-5995-6494", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4d84c40612d48f280d4ead25558d835.json"}}, {"family": "Sastre", "given": "Leandro", "initials": "L"}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.json"}}, {"family": "de Vega", "given": "Miguel", "initials": "M", "orcid": "0000-0003-1285-7549", "researcher": {"href": "https://publications.scilifelab.se/researcher/77e5f3b41f634728b525ff94b0496bc4.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Michel", "given": "Maurice", "initials": "M", "orcid": "0000-0003-3261-2493", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f7cb5d695254481b745f86a824ac1b5.json"}}], "type": "journal article", "published": "2025-10-28", "journal": {"title": "RSC Chem Biol", "issn": "2633-0679", "issn-l": null}, "abstract": "Bifunctional DNA glycosylases employ an active site lysine or the N-terminus to form a Schiff base with an abasic (AP) site base excision repair intermediate. For 8-oxoguanine DNA glycosylase 1 (OGG1), cleaving this reversible structure is the rate-determining step in the initiation of 8-oxoguanine (8-oxoG) repair in DNA. Evolution has led OGG1 to use a product-assisted catalysis approach, where the excised 8-oxoG acts as a Br\u00f8nsted base for cleavage of a Schiff base intermediate. However, the physicochemical properties of 8-oxoG significantly limit the inherent enzymatic turnover leading to a weak, cellularly absent, AP lyase activity. We hypothesized that chemical synthesis of purine analogues enables access to complex structures that are suitable as product-like catalysts. Herein, the nucleobase landscape is profiled for its potential to increase OGG1 Schiff base cleavage. 8-Substituted 6-thioguanines emerge as potent and selective scaffolds enabling OGG1 to cleave AP sites opposite any canonical nucleobase by \u03b2-elimination. This effectively broadens the enzymatic substrate scope of OGG1, shaping a complete, artificial AP-lyase function. In addition, a second class of compounds, 6-substituted pyrazolo-[3,4-d]-pyrimidines, stimulate OGG1 function at high pH, while thioguanines govern enzymatic control at acidic pH. This enables up to 20-fold increased enzyme turnover and a de novo OGG1 \u03b2-elimination in conditions commonly not tolerated. The tool compounds employed here are non-toxic in cells and stimulate the repair of AP sites through a natural, APE1 dependent pathway, as opposed to previously reported \u03b2,\u03b4-lyase stimulator TH10785.", "doi": "10.1039/d4cb00323c", "pmid": "41195166", "labels": {"Chemical Biology Consortium Sweden": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12584757"}, {"db": "pii", "key": "d4cb00323c"}], "notes": [], "created": "2025-11-25T11:35:44.104Z", "modified": "2025-11-27T13:32:01.339Z"}, {"entity": "publication", "iuid": "85de2289fd19407dad34e21e261cb987", "links": {"self": {"href": "https://publications.scilifelab.se/publication/85de2289fd19407dad34e21e261cb987.json"}, "display": {"href": "https://publications.scilifelab.se/publication/85de2289fd19407dad34e21e261cb987"}}, "title": "Detection and characterisation of ligand-induced conformational changes in acetylcholine binding proteins using biosensors and X-ray crystallography.", "authors": [{"family": "FitzGerald", "given": "Edward A", "initials": "EA", "orcid": "0000-0002-0603-1241", "researcher": {"href": "https://publications.scilifelab.se/researcher/66338852ec3d475380ba5bf6d50be1b7.json"}}, {"family": "Cederfelt", "given": "Daniela", "initials": "D"}, {"family": "Kovryzhenko", "given": "Daria", "initials": "D"}, {"family": "Boronat", "given": "Pierre", "initials": "P"}, {"family": "Lund", "given": "Bjarte Aarmo", "initials": "BA", "orcid": "0000-0001-9141-0555", "researcher": {"href": "https://publications.scilifelab.se/researcher/941bad0f031c47cea46b35bc049d778a.json"}}, {"family": "Dobritzsch", "given": "Doreen", "initials": "D"}, {"family": "Hennig", "given": "Sven", "initials": "S", "orcid": "0000-0002-8297-6845", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a64c0c8bf0e457d8251a98f54fc79df.json"}}, {"family": "Paseiro", "given": "Pablo Porragas", "initials": "PP"}, {"family": "de Esch", "given": "Iwan J P", "initials": "IJP"}, {"family": "Danielson", "given": "U Helena", "initials": "UH", "orcid": "0000-0003-2728-0340", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2bf7dffedf44237807c23718c72efa6.json"}}], "type": "journal article", "published": "2025-10-01", "journal": {"title": "RSC Chem Biol", "issn": "2633-0679", "volume": "6", "issue": "10", "pages": "1625-1639", "issn-l": null}, "abstract": "Analysis of ligand-induced structural changes in proteins is challenging due to the lack of experimental methods suited for detection and characterisation of both ligand binding and induced structural changes. We have explored biosensors with different detection principles to study interactions between ligands and acetylcholine binding proteins (AChBPs), soluble homologues of Cys-loop ligand gated ion channels (LGICs) that undergo similar structural changes as LGICs upon ligand binding. X-ray crystallography was used to identify binding sites and establish if the detected conformational changes involved small changes in loop C or major structural changes in the pentamer associated with ion channel opening. Experiments were initially focused on ligands exhibiting complex surface plasmon resonance (SPR) biosensor sensorgrams or detected by second harmonic generation (SHG) biosensor analysis. Surface acoustic wave (SAW) and SHG biosensors confirmed that complexities in SPR data were indeed due to ligand-induced conformational changes. Grating coupled interferometry (GCI) biosensor sensorgrams were less complex, despite similar detection principles. switchSENSE biosensor analysis revealed that ligands resulted in either a compaction or expansion of the protein structure. X-ray crystallography of the protein-ligand complexes was only successful for 7 out of 12 ligands, despite nM-\u03bcM affinities. Crystals were not obtained for the two compounds shown by SHG analysis to induce large structural changes, while electron densities were not seen in the structures for some ligands. The work presented herein shows that several biosensor technologies have a unique capability to detect and discriminate binding and ligand induced conformational changes in proteins, also when interactions are rapid, weak and structural changes are small. However, they are complementary and provide different information.", "doi": "10.1039/d5cb00041f", "pmid": "40896114", "labels": {"Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC12394895"}, {"db": "pii", "key": "d5cb00041f"}], "notes": [], "created": "2025-11-18T22:03:28.805Z", "modified": "2025-11-18T22:03:29.261Z"}, {"entity": "publication", "iuid": "203d08d6d1304755a054814170303345", "links": {"self": {"href": "https://publications.scilifelab.se/publication/203d08d6d1304755a054814170303345.json"}, "display": {"href": "https://publications.scilifelab.se/publication/203d08d6d1304755a054814170303345"}}, "title": "Plasma membrane labelling efficiency, internalization and partitioning of functionalized fluorescent lipids as a function of lipid structure.", "authors": [{"family": "Sezgin", "given": "Erdinc", "initials": "E", "orcid": "0000-0002-4915-388X", "researcher": {"href": "https://publications.scilifelab.se/researcher/34d3b05d68d64f698ff08dc655d2fe26.json"}}], "type": "journal article", "published": "2025-09-01", "journal": {"title": "RSC Chem Biol", "issn": "2633-0679", "issn-l": null}, "abstract": "Labeling the plasma membrane for advanced imaging remains a significant challenge. For time-lapse live cell imaging, probe internalization and photobleaching are major limitations affecting most membrane-specific dyes. In fixed or permeabilized cells, many membrane probes either lose signal after fixation or fail to remain localized to the plasma membrane. Thus, improved probes are critically needed for applications in spatial biology. In this study, we systematically compared a range of custom-synthesized and commercially available lipid-based probes for their efficiency in labeling the plasma membrane in live, fixed, and permeabilized cells. We identified a superior probe, which outperformed others due to its lipid structure. This comparison provides insights into ideal lipid probes for visualizing the plasma membrane using advanced imaging techniques.", "doi": "10.1039/d5cb00116a", "pmid": "40927427", "labels": {"Integrated Microscopy Technologies Stockholm": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12415625"}, {"db": "pii", "key": "d5cb00116a"}], "notes": [], "created": "2025-09-13T11:07:39.964Z", "modified": "2025-09-15T10:04:02.296Z"}, {"entity": "publication", "iuid": "bb84c8f0da2546d197d9be264a758437", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bb84c8f0da2546d197d9be264a758437.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bb84c8f0da2546d197d9be264a758437"}}, "title": "Design and application of a fluorescent probe for imaging of endogenous Bruton's tyrosine kinase with preserved enzymatic activity.", "authors": [{"family": "Valaka", "given": "Anna P", "initials": "AP", "orcid": "0009-0008-7007-6971", "researcher": {"href": "https://publications.scilifelab.se/researcher/90c945c6f7b84acc8fc0097ec194332e.json"}}, {"family": "Nystr\u00f6m", "given": "Hampus", "initials": "H", "orcid": "0009-0006-8139-3839", "researcher": {"href": "https://publications.scilifelab.se/researcher/a763c1525ea446bd913291a2599ea9f7.json"}}, {"family": "H\u00e5versen", "given": "Liliana", "initials": "L"}, {"family": "Benitez-Martin", "given": "Carlos", "initials": "C", "orcid": "0000-0003-1821-9388", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1fcdd6e053b462998fe7f463be60d96.json"}}, {"family": "Sch\u00e4fer", "given": "Clara", "initials": "C", "orcid": "0000-0001-7634-3980", "researcher": {"href": "https://publications.scilifelab.se/researcher/58fcf0b78e574d5f9a52fcab14632117.json"}}, {"family": "Jang", "given": "Woo Suk", "initials": "WS"}, {"family": "Camponeschi", "given": "Alessandro", "initials": "A", "orcid": "0000-0002-6472-2438", "researcher": {"href": "https://publications.scilifelab.se/researcher/ccbaffafd6a24f4abed1e402219fa472.json"}}, {"family": "Andr\u00e9asson", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4695-7943", "researcher": {"href": "https://publications.scilifelab.se/researcher/28eb5affb5664c54be9171dfce6bea15.json"}}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J", "orcid": "0000-0003-0786-8091", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e85f6d287ce4c60a7b35b287efb4f79.json"}}, {"family": "Gr\u00f8tli", "given": "Morten", "initials": "M", "orcid": "0000-0003-3621-4222", "researcher": {"href": "https://publications.scilifelab.se/researcher/764706606bcb4afba1150af332c0f124.json"}}], "type": "journal article", "published": "2025-04-02", "journal": {"title": "RSC Chem Biol", "issn": "2633-0679", "issn-l": null, "volume": "6", "issue": "4", "pages": "618-629"}, "abstract": "Fluorophore integration into proteins within living cells is essential for exploring proteins in their natural environment. Bruton's tyrosine kinase (BTK), is a validated oncology target and is crucial for B cell proliferation and activation. Developing BTK-labelling probes is key to understand BTK's dynamic signalling pathway. In this work, we aimed to develop a novel fluorescent labelling probe for endogenous BTK imaging while preserving its enzymatic activity. Evobrutinib, a second-generation BTK inhibitor with high selectivity, was chosen as the scaffold. We designed two probes, Evo-1 and Evo-2, with a BODIPY fluorescent group, guided by molecular modelling. The synthesis was achieved using optimised Suzuki-Miyaura cross-coupling and amide coupling reactions. Biochemical assays confirmed covalent binding to Cys481 of BTK while preserving its enzymatic activity. Labelling of endogenous BTK with Evo-2 with reduced off-target effects in Ramos cells was validated in cellular assays. The dynamic signalling pathway of BTK in its native environment was investigated by confocal microscopy with Evo-2. This methodology is a valuable asset in the chemical biology toolbox for studying protein dynamics and interactions in real time without interfering with the protein activity.", "doi": "10.1039/d4cb00313f", "pmid": "40026844", "labels": {"Glycoproteomics and MS Proteomics": "Service", "Integrated Microscopy Technologies Gothenburg": "Service", "Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11867108"}, {"db": "pii", "key": "d4cb00313f"}], "notes": [], "created": "2025-10-23T16:03:12.593Z", "modified": "2025-11-27T13:34:09.343Z"}, {"entity": "publication", "iuid": "70c1a704e3354fe09fbe0185d3d28f8c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/70c1a704e3354fe09fbe0185d3d28f8c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/70c1a704e3354fe09fbe0185d3d28f8c"}}, "title": "Mapping the energy landscape of protein-ligand binding via linear free energy relationships determined by protein NMR relaxation dispersion.", "authors": [{"family": "Stenstr\u00f6m", "given": "Olof", "initials": "O"}, {"family": "Diehl", "given": "Carl", "initials": "C"}, {"family": "Modig", "given": "Kristofer", "initials": "K"}, {"family": "Nilsson", "given": "Ulf J", "initials": "UJ", "orcid": "0000-0001-5815-9522", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d23150eb03f42ae866d49ff331ebc79.json"}}, {"family": "Akke", "given": "Mikael", "initials": "M", "orcid": "0000-0002-2395-825X", "researcher": {"href": "https://publications.scilifelab.se/researcher/e36b418e03154b90a8722670bed9e81a.json"}}], "type": "journal article", "published": "2021-02-01", "journal": {"title": "RSC Chem Biol", "issn": "2633-0679", "volume": "2", "issue": "1", "pages": "259-265", "issn-l": null}, "abstract": "Biochemical signaling is mediated by complexes between macromolecular receptors and their ligands, with the duration of the signal being directly related to the lifetime of the ligand-receptor complex. In the field of drug design, the recognition that drug efficacy in vivo depends on the lifetime of the drug-protein complex has spawned the concept of designing drugs with particular binding kinetics. To advance this field it is critical to investigate how the molecular details of designed ligands might affect the binding kinetics, as well as the equilibrium binding constant. Here we use protein NMR relaxation dispersion to determine linear free energy relationships involving the on- and off-rates and the affinity for a series of congeneric ligands targeting the carbohydrate recognition domain of galectin-3. Using this approach we determine the energy landscape and the position of the transition state along the reaction coordinate of protein-ligand binding. The results show that ligands exhibiting reduced off-rates achieve this by primarily stabilizing the bound state, but do not affect the transition state to any greater extent. The transition state forms early, that is, it is located significantly closer to the free state than to the bound state, suggesting a critical role of desolvation. Furthermore, the data suggest that different subclasses of ligands show different behavior with respect to these characteristics.", "doi": "10.1039/d0cb00229a", "pmid": "34458786", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pii", "key": "d0cb00229a"}, {"db": "pmc", "key": "PMC8341105"}], "notes": [], "created": "2021-12-08T15:47:13.952Z", "modified": "2025-10-17T13:03:56.258Z"}], "created": "2021-12-08T15:47:13.989Z", "modified": "2021-12-08T15:47:13.989Z"}