{"entity": "researcher", "timestamp": "2026-10-05T21:24:11.535Z", "family": "FitzGerald", "given": "Edward A", "initials": "EA", "orcid": "0000-0002-0603-1241", "affiliations": ["Department of Chemistry \u2013 BMC", "Uppsala University", "Uppsala", "Sweden", "Beactica Therapeutics"], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/66338852ec3d475380ba5bf6d50be1b7.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/66338852ec3d475380ba5bf6d50be1b7"}}, "publications": [{"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": "cdb649940de34aaf9bd52daedf59043f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cdb649940de34aaf9bd52daedf59043f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cdb649940de34aaf9bd52daedf59043f"}}, "title": "Discovery of an Allosteric Ligand Binding Site in SMYD3 Lysine Methyltransferase.", "authors": [{"family": "Talibov", "given": "Vladimir O", "initials": "VO", "orcid": "0000-0002-1135-2744", "researcher": {"href": "https://publications.scilifelab.se/researcher/e2cdaf464ed342d695baf33c19690518.json"}}, {"family": "Fabini", "given": "Edoardo", "initials": "E", "orcid": "0000-0001-8688-2208", "researcher": {"href": "https://publications.scilifelab.se/researcher/388d219ceead49ae9b2ebe5a22af582c.json"}}, {"family": "FitzGerald", "given": "Edward A", "initials": "EA", "orcid": "0000-0002-0603-1241", "researcher": {"href": "https://publications.scilifelab.se/researcher/66338852ec3d475380ba5bf6d50be1b7.json"}}, {"family": "Tedesco", "given": "Daniele", "initials": "D", "orcid": "0000-0003-2585-7791", "researcher": {"href": "https://publications.scilifelab.se/researcher/2eb39e0e14fe43e5aa6a8be62c5373bf.json"}}, {"family": "Cederfeldt", "given": "Daniela", "initials": "D"}, {"family": "Talu", "given": "Martin J", "initials": "MJ"}, {"family": "Rachman", "given": "Moira M", "initials": "MM", "orcid": "0000-0003-3671-8885", "researcher": {"href": "https://publications.scilifelab.se/researcher/b1f1b1f3345049d18bc74b87122ef7f9.json"}}, {"family": "Mihalic", "given": "Filip", "initials": "F"}, {"family": "Manoni", "given": "Elisabetta", "initials": "E"}, {"family": "Naldi", "given": "Marina", "initials": "M", "orcid": "0000-0003-4468-2974", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e95a716834e4fbe86fa28fd0fde8f4a.json"}}, {"family": "Sanese", "given": "Paola", "initials": "P"}, {"family": "Forte", "given": "Giovanna", "initials": "G"}, {"family": "Lepore Signorile", "given": "Martina", "initials": "M"}, {"family": "Barril", "given": "Xavier", "initials": "X"}, {"family": "Simone", "given": "Cristiano", "initials": "C"}, {"family": "Bartolini", "given": "Manuela", "initials": "M", "orcid": "0000-0002-2890-3856", "researcher": {"href": "https://publications.scilifelab.se/researcher/10a0e31d3d414cf6a0b274e0a7495d32.json"}}, {"family": "Dobritzsch", "given": "Doreen", "initials": "D"}, {"family": "Del Rio", "given": "Alberto", "initials": "A", "orcid": "0000-0002-1890-6797", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b547aaccb804575b09a0ded5282f7c8.json"}}, {"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": "2021-05-04", "journal": {"title": "ChemBioChem", "issn": "1439-7633", "volume": "22", "issue": "9", "pages": "1597-1608", "issn-l": "1439-4227"}, "abstract": "SMYD3 is a multifunctional epigenetic enzyme with lysine methyltransferase activity and various interaction partners. It is implicated in the pathophysiology of cancers but with an unclear mechanism. To discover tool compounds for clarifying its biochemistry and potential as a therapeutic target, a set of drug-like compounds was screened in a biosensor-based competition assay. Diperodon was identified as an allosteric ligand; its R and S enantiomers were isolated, and their affinities to SMYD3 were determined (KD =42 and 84 \u03bcM, respectively). Co-crystallization revealed that both enantiomers bind to a previously unidentified allosteric site in the C-terminal protein binding domain, consistent with its weak inhibitory effect. No competition between diperodon and HSP90 (a known SMYD3 interaction partner) was observed although SMYD3-HSP90 binding was confirmed (KD =13 \u03bcM). Diperodon clearly represents a novel starting point for the design of tool compounds interacting with a druggable allosteric site, suitable for the exploration of noncatalytic SMYD3 functions and therapeutics with new mechanisms of action.", "doi": "10.1002/cbic.202000736", "pmid": "33400854", "labels": {"Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8248052"}], "notes": [], "created": "2021-12-08T12:06:32.774Z", "modified": "2025-10-17T13:05:07.894Z"}, {"entity": "publication", "iuid": "4e30c827221d45299555816bce6ebaf2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4e30c827221d45299555816bce6ebaf2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4e30c827221d45299555816bce6ebaf2"}}, "title": "Discovery of fragments inducing conformational effects in dynamic proteins using a second-harmonic generation biosensor", "authors": [{"family": "FitzGerald", "given": "Edward A", "initials": "EA", "orcid": "0000-0002-0603-1241", "researcher": {"href": "https://publications.scilifelab.se/researcher/66338852ec3d475380ba5bf6d50be1b7.json"}}, {"family": "Butko", "given": "Margaret T", "initials": "MT"}, {"family": "Boronat", "given": "Pierre", "initials": "P"}, {"family": "Cederfelt", "given": "Daniela", "initials": "D"}, {"family": "Abramsson", "given": "Mia", "initials": "M", "orcid": "0000-0002-8184-0145", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b13d2ef38bf49d386f12ad170ae939d.json"}}, {"family": "Ludviksdottir", "given": "Hildur", "initials": "H"}, {"family": "van Muijlwijk-Koezen", "given": "Jacqueline E", "initials": "JE"}, {"family": "de Esch", "given": "Iwan J P", "initials": "IJP"}, {"family": "Dobritzsch", "given": "Doreen", "initials": "D"}, {"family": "Young", "given": "Tracy", "initials": "T"}, {"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": "2021-00-00", "journal": {"title": "RSC Adv.", "issn": "2046-2069", "issn-l": "2046-2069", "volume": "11", "issue": "13", "pages": "7527-7537"}, "abstract": null, "doi": "10.1039/d0ra09844b", "pmid": null, "labels": {"Chemical Biology Consortium Sweden": "Service", "Drug Discovery and Development": null}, "xrefs": [], "notes": [], "created": "2021-12-02T12:28:50.784Z", "modified": "2025-10-17T13:05:07.930Z"}]}