{"entity": "researcher", "timestamp": "2026-04-20T03:42:13.498Z", "family": "Sch\u00fcler", "given": "Herwig", "initials": "H", "orcid": "0000-0003-4059-3501", "affiliations": ["Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/f49b25ddfc934f3ca41020c3f38c6bfc.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/f49b25ddfc934f3ca41020c3f38c6bfc"}}, "publications": [{"entity": "publication", "iuid": "3fe1414d1f404aa7868cec9204360adb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3fe1414d1f404aa7868cec9204360adb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3fe1414d1f404aa7868cec9204360adb"}}, "title": "Regulation of ADP-ribosyltransferase activity by ART domain dimerization in PARP15", "authors": [{"family": "Ebenwaldner", "given": "Carmen", "initials": "C", "orcid": "0000-0002-7919-2994", "researcher": {"href": "https://publications.scilifelab.se/researcher/e2aedf9747ff49eb904e353f28847b61.json"}}, {"family": "Garc\u00eda Saura", "given": "Antonio Gin\u00e9s", "initials": "AG"}, {"family": "Ekstr\u00f6m", "given": "Simon", "initials": "S", "orcid": "0000-0002-7694-285X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6416b323664f4126b70067193d7b8347.json"}}, {"family": "Bernfur", "given": "Katja", "initials": "K", "orcid": "0000-0002-7927-9563", "researcher": {"href": "https://publications.scilifelab.se/researcher/4600cd5ea61b41e4ab9b85af90fb41b4.json"}}, {"family": "Moche", "given": "Martin", "initials": "M"}, {"family": "Logan", "given": "Derek T", "initials": "DT", "orcid": "0000-0002-0098-8560", "researcher": {"href": "https://publications.scilifelab.se/researcher/da2734243cdb4142be696e5a82e788ae.json"}}, {"family": "Cohen", "given": "Michael S", "initials": "MS", "orcid": "0000-0002-7636-4156", "researcher": {"href": "https://publications.scilifelab.se/researcher/352749e458584319ab9d870abec5d90f.json"}}, {"family": "Sch\u00fcler", "given": "Herwig", "initials": "H", "orcid": "0000-0003-4059-3501", "researcher": {"href": "https://publications.scilifelab.se/researcher/f49b25ddfc934f3ca41020c3f38c6bfc.json"}}], "type": "journal-article", "published": "2025-10-29", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "16", "issue": "1", "pages": null}, "abstract": null, "doi": "10.1038/s41467-025-65315-9", "pmid": null, "labels": {"Structural Proteomics": "Collaborative"}, "xrefs": [], "notes": [], "created": "2024-11-27T17:26:39.850Z", "modified": "2025-11-26T16:30:32.588Z"}, {"entity": "publication", "iuid": "34c177a6bf874180a7803c15a79588ae", "links": {"self": {"href": "https://publications.scilifelab.se/publication/34c177a6bf874180a7803c15a79588ae.json"}, "display": {"href": "https://publications.scilifelab.se/publication/34c177a6bf874180a7803c15a79588ae"}}, "title": "System-wide identification and prioritization of enzyme substrates by thermal analysis.", "authors": [{"family": "Saei", "given": "Amir Ata", "initials": "AA", "orcid": "0000-0002-2639-6328", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1694ffdcd94a55b6c172a854706e0f.json"}}, {"family": "Beusch", "given": "Christian M", "initials": "CM", "orcid": "0000-0001-9100-8283", "researcher": {"href": "https://publications.scilifelab.se/researcher/278e50b11a3c4ef69b6e2708f99b5f3e.json"}}, {"family": "Sabatier", "given": "Pierre", "initials": "P", "orcid": "0000-0002-2734-1791", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a75556311084e2b827ab1f646d7a16c.json"}}, {"family": "Wells", "given": "Juan Astorga", "initials": "JA", "orcid": "0000-0003-1017-8841", "researcher": {"href": "https://publications.scilifelab.se/researcher/14530d9aa03747858976b4889e959fe5.json"}}, {"family": "Gharibi", "given": "Hassan", "initials": "H", "orcid": "0000-0002-3072-4929", "researcher": {"href": "https://publications.scilifelab.se/researcher/b85179acfa7e4916ad40ae478d6dcc0a.json"}}, {"family": "Meng", "given": "Zhaowei", "initials": "Z"}, {"family": "Chernobrovkin", "given": "Alexey", "initials": "A", "orcid": "0000-0001-7709-0161", "researcher": {"href": "https://publications.scilifelab.se/researcher/d36b29dc4fd44785b36b9baa9e291757.json"}}, {"family": "Rodin", "given": "Sergey", "initials": "S"}, {"family": "N\u00e4reoja", "given": "Katja", "initials": "K"}, {"family": "Thorsell", "given": "Ann-Gerd", "initials": "A"}, {"family": "Karlberg", "given": "Tobias", "initials": "T"}, {"family": "Cheng", "given": "Qing", "initials": "Q"}, {"family": "Lundstr\u00f6m", "given": "Susanna L", "initials": "SL"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "V\u00e9gv\u00e1ri", "given": "\u00c1kos", "initials": "\u00c1", "orcid": "0000-0002-1287-0906", "researcher": {"href": "https://publications.scilifelab.se/researcher/74be6e7c877e4f0da6c7ed3747f3ef9d.json"}}, {"family": "Arn\u00e9r", "given": "Elias S J", "initials": "ESJ", "orcid": "0000-0002-4807-6114", "researcher": {"href": "https://publications.scilifelab.se/researcher/70a545effced47da8a5192a7472ceb8f.json"}}, {"family": "Sch\u00fcler", "given": "Herwig", "initials": "H", "orcid": "0000-0003-4059-3501", "researcher": {"href": "https://publications.scilifelab.se/researcher/f49b25ddfc934f3ca41020c3f38c6bfc.json"}}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "journal article", "published": "2021-02-26", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "12", "issue": "1", "pages": "1296"}, "abstract": "Despite the immense importance of enzyme-substrate reactions, there is a lack of general and unbiased tools for identifying and prioritizing substrate proteins that are modified by the enzyme on the structural level. Here we describe a high-throughput unbiased proteomics method called System-wide Identification and prioritization of Enzyme Substrates by Thermal Analysis (SIESTA). The approach assumes that the enzymatic post-translational modification of substrate proteins is likely to change their thermal stability. In our proof-of-concept studies, SIESTA successfully identifies several known and novel substrate candidates for selenoprotein thioredoxin reductase 1, protein kinase B (AKT1) and poly-(ADP-ribose) polymerase-10 systems. Wider application of SIESTA can enhance our understanding of the role of enzymes in homeostasis and disease, opening opportunities to investigate the effect of post-translational modifications on signal transduction and facilitate drug discovery.", "doi": "10.1038/s41467-021-21540-6", "pmid": "33637753", "labels": {"Chemical Proteomics": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-021-21540-6"}, {"db": "pmc", "key": "PMC7910609"}], "notes": [], "created": "2020-01-23T10:41:17.194Z", "modified": "2021-12-09T09:37:12.987Z"}, {"entity": "publication", "iuid": "f870d06d8746421ebbb308e2a749cf8e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f870d06d8746421ebbb308e2a749cf8e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f870d06d8746421ebbb308e2a749cf8e"}}, "title": "Engineering Af1521 improves ADP-ribose binding and identification of ADP-ribosylated proteins.", "authors": [{"family": "Nowak", "given": "Kathrin", "initials": "K"}, {"family": "Rosenthal", "given": "Florian", "initials": "F"}, {"family": "Karlberg", "given": "Tobias", "initials": "T"}, {"family": "B\u00fctepage", "given": "Mareike", "initials": "M"}, {"family": "Thorsell", "given": "Ann-Gerd", "initials": "AG"}, {"family": "Dreier", "given": "Birgit", "initials": "B"}, {"family": "Grossmann", "given": "Jonas", "initials": "J"}, {"family": "Sobek", "given": "Jens", "initials": "J"}, {"family": "Imhof", "given": "Ralph", "initials": "R"}, {"family": "L\u00fcscher", "given": "Bernhard", "initials": "B", "orcid": "0000-0002-9622-8709", "researcher": {"href": "https://publications.scilifelab.se/researcher/b777138c7e7740c5926a5385997dec9c.json"}}, {"family": "Sch\u00fcler", "given": "Herwig", "initials": "H", "orcid": "0000-0003-4059-3501", "researcher": {"href": "https://publications.scilifelab.se/researcher/f49b25ddfc934f3ca41020c3f38c6bfc.json"}}, {"family": "Pl\u00fcckthun", "given": "Andreas", "initials": "A", "orcid": "0000-0003-4191-5306", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f67a65bf469443a89665bd244bfd0f7.json"}}, {"family": "Leslie Pedrioli", "given": "Deena M", "initials": "DM", "orcid": "0000-0003-2342-8010", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d2182b2344f4758abdf6fb8a05a39eb.json"}}, {"family": "Hottiger", "given": "Michael O", "initials": "MO", "orcid": "0000-0002-7323-2270", "researcher": {"href": "https://publications.scilifelab.se/researcher/8cc0bd6ccac3417fb8c04e02a5833efd.json"}}], "type": "journal article", "published": "2020-10-15", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "5199", "issn-l": "2041-1723"}, "abstract": "Protein ADP-ribosylation is a reversible post-translational modification that regulates important cellular functions. The identification of modified proteins has proven challenging and has mainly been achieved via enrichment methodologies. Random mutagenesis was used here to develop an engineered Af1521 ADP-ribose binding macro domain protein with 1000-fold increased affinity towards ADP-ribose. The crystal structure reveals that two point mutations K35E and Y145R form a salt bridge within the ADP-ribose binding domain. This forces the proximal ribose to rotate within the binding pocket and, as a consequence, improves engineered Af1521 ADPr-binding affinity. Its use in our proteomic ADP-ribosylome workflow increases the ADP-ribosylated protein identification rates and yields greater ADP-ribosylome coverage. Furthermore, generation of an engineered Af1521 Fc fusion protein confirms the improved detection of cellular ADP-ribosylation by immunoblot and immunofluorescence. Thus, this engineered isoform of Af1521 can also serve as a valuable tool for the analysis of cellular ADP-ribosylation under in vivo conditions.", "doi": "10.1038/s41467-020-18981-w", "pmid": "33060572", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7566600"}, {"db": "pii", "key": "10.1038/s41467-020-18981-w"}], "notes": [], "created": "2024-04-03T14:24:02.267Z", "modified": "2024-04-03T14:24:02.738Z"}, {"entity": "publication", "iuid": "0bb3726f467a454f93f1ffed642bf61b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0bb3726f467a454f93f1ffed642bf61b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0bb3726f467a454f93f1ffed642bf61b"}}, "title": "A Focused DNA-Encoded Chemical Library for the Discovery of Inhibitors of NAD+-Dependent Enzymes.", "authors": [{"family": "Yuen", "given": "Lik Hang", "initials": "LH"}, {"family": "Dana", "given": "Srikanta", "initials": "S", "orcid": "0000-0003-0503-3082", "researcher": {"href": "https://publications.scilifelab.se/researcher/eec7ed2fde2649efb5dd98fa8d38790f.json"}}, {"family": "Liu", "given": "Yu", "initials": "Y"}, {"family": "Bloom", "given": "Samuel I", "initials": "SI"}, {"family": "Thorsell", "given": "Ann-Gerd", "initials": "AG"}, {"family": "Neri", "given": "Dario", "initials": "D"}, {"family": "Donato", "given": "Anthony J", "initials": "AJ"}, {"family": "Kireev", "given": "Dmitri", "initials": "D", "orcid": "0000-0001-8479-8555", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e18a814164e44b39fb105bc963fd329.json"}}, {"family": "Sch\u00fcler", "given": "Herwig", "initials": "H", "orcid": "0000-0003-4059-3501", "researcher": {"href": "https://publications.scilifelab.se/researcher/f49b25ddfc934f3ca41020c3f38c6bfc.json"}}, {"family": "Franzini", "given": "Raphael M", "initials": "RM", "orcid": "0000-0001-6772-5119", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e2a980af3104379b2614d765dc66e23.json"}}], "type": "journal article", "published": "2019-04-03", "journal": {"title": "J. Am. Chem. Soc.", "issn": "1520-5126", "volume": "141", "issue": "13", "pages": "5169-5181", "issn-l": "0002-7863"}, "abstract": "DNA-encoded chemical libraries are increasingly used in pharmaceutical research because they enable the rapid discovery of synthetic protein ligands. Here we explored whether target-class focused DNA-encoded chemical libraries can be cost-effective tools to achieve robust screening productivity for a series of proteins. The study revealed that a DNA-encoded library designed for NAD+-binding pockets (NADEL) effectively sampled the chemical binder space of enzymes with ADP-ribosyltransferase activity. The extracted information directed the synthesis of inhibitors for several enzymes including PARP15 and SIRT6. The high dissimilarity of NADEL screening fingerprints for different proteins translated into inhibitors that showed selectivity for their target. The discovery of patterns of enriched structures for six out of eight tested proteins is remarkable for a library of 58 302 DNA-tagged structures and illustrates the prospect of focused DNA-encoded libraries as economic alternatives to large library platforms.", "doi": "10.1021/jacs.8b08039", "pmid": "30855951", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [], "notes": [], "created": "2024-04-03T14:25:58.272Z", "modified": "2024-04-03T14:25:59.429Z"}, {"entity": "publication", "iuid": "e89bae0bea434005ba4ddc7ceb519507", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e89bae0bea434005ba4ddc7ceb519507.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e89bae0bea434005ba4ddc7ceb519507"}}, "title": "14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a hydrophobic surface.", "authors": [{"family": "Karlberg", "given": "Tobias", "initials": "T"}, {"family": "Hornyak", "given": "Peter", "initials": "P"}, {"family": "Pinto", "given": "Ana Filipa", "initials": "AF"}, {"family": "Milanova", "given": "Stefina", "initials": "S"}, {"family": "Ebrahimi", "given": "Mahsa", "initials": "M"}, {"family": "Lindberg", "given": "Mikael", "initials": "M"}, {"family": "P\u00fcllen", "given": "Nikolai", "initials": "N"}, {"family": "Nordstr\u00f6m", "given": "Axel", "initials": "A", "orcid": "0000-0003-2314-3322", "researcher": {"href": "https://publications.scilifelab.se/researcher/718995e4280a4976831170548a64d96f.json"}}, {"family": "L\u00f6verli", "given": "Elinor", "initials": "E"}, {"family": "Caraballo", "given": "R\u00e9mi", "initials": "R"}, {"family": "Wong", "given": "Emily V", "initials": "EV"}, {"family": "N\u00e4reoja", "given": "Katja", "initials": "K"}, {"family": "Thorsell", "given": "Ann-Gerd", "initials": "AG"}, {"family": "Elofsson", "given": "Mikael", "initials": "M"}, {"family": "De La Cruz", "given": "Enrique M", "initials": "EM"}, {"family": "Bj\u00f6rkegren", "given": "Camilla", "initials": "C", "orcid": "0000-0001-7354-9270", "researcher": {"href": "https://publications.scilifelab.se/researcher/0bb62675186e4e13b6eb47c10c307ab8.json"}}, {"family": "Sch\u00fcler", "given": "Herwig", "initials": "H", "orcid": "0000-0003-4059-3501", "researcher": {"href": "https://publications.scilifelab.se/researcher/f49b25ddfc934f3ca41020c3f38c6bfc.json"}}], "type": "journal article", "published": "2018-09-17", "journal": {"volume": "9", "issn": "2041-1723", "issue": "1", "pages": "3785", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "Pseudomonas are a common cause of hospital-acquired infections that may be lethal. ADP-ribosyltransferase activities of Pseudomonas exotoxin-S and -T depend on 14-3-3 proteins inside the host cell. By binding in the 14-3-3 phosphopeptide binding groove, an amphipathic C-terminal helix of ExoS and ExoT has been thought to be crucial for their activation. However, crystal structures of the 14-3-3\u03b2:ExoS and -ExoT complexes presented here reveal an extensive hydrophobic interface that is sufficient for complex formation and toxin activation. We show that C-terminally truncated ExoS ADP-ribosyltransferase domain lacking the amphipathic binding motif is active when co-expressed with 14-3-3. Moreover, swapping the amphipathic C-terminus with a fragment from Vibrio Vis toxin creates a 14-3-3 independent toxin that ADP-ribosylates known ExoS targets. Finally, we show that 14-3-3 stabilizes ExoS against thermal aggregation. Together, this indicates that 14-3-3 proteins activate exotoxin ADP-ribosyltransferase domains by chaperoning their hydrophobic surfaces independently of the amphipathic C-terminal segment.", "doi": "10.1038/s41467-018-06194-1", "pmid": "30224724", "labels": {"Protein Science Facility (PSF)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-018-06194-1"}, {"db": "pmc", "key": "PMC6141617"}], "notes": [], "created": "2018-09-18T08:55:18.810Z", "modified": "2024-01-16T13:48:45.502Z"}]}