{"entity": "researcher", "timestamp": "2026-08-20T20:36:35.311Z", "family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "affiliations": ["Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3"}}, "publications": [{"entity": "publication", "iuid": "172755f770e243579d9d401b29efec67", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/172755f770e243579d9d401b29efec67.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/172755f770e243579d9d401b29efec67"}}, "title": "Giving an Enzyme Scissors: Serotonin Derivatives as Potent Organocatalytic Switches for DNA Repair Enzyme OGG1.", "authors": [{"family": "Varga", "given": "Marek", "initials": "M", "orcid": "0000-0002-9685-8145", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/707532fc225c49d1b2d4f9bec632e13f.json"}}, {"family": "Ortis", "given": "Florian", "initials": "F"}, {"family": "Del Prado", "given": "Alicia", "initials": "A", "orcid": "0000-0002-5480-0367", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7625321e94ab4cb5ba256de247cd0fcd.json"}}, {"family": "Eddershaw", "given": "Alice", "initials": "A", "orcid": "0000-0002-8381-4135", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bef07e3914ad492d99119e687845f3c4.json"}}, {"family": "Scaletti Hutchinson", "given": "Emma", "initials": "E", "orcid": "0000-0002-8741-8981", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/77be7f5d51564a75a753579e976c7c72.json"}}, {"family": "Hank", "given": "Emily C", "initials": "EC", "orcid": "0000-0002-3777-4697", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2b412977f2364bef9ec63aa5e552331a.json"}}, {"family": "Zhou", "given": "Kaixin", "initials": "K"}, {"family": "Rudolfov\u00e1", "given": "Nat\u00e1lie", "initials": "N"}, {"family": "Dodaro", "given": "Alessia", "initials": "A"}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Karsten", "given": "Stella", "initials": "S"}, {"family": "Mamonov", "given": "Kirill", "initials": "K"}, {"family": "Ahmed", "given": "Sara H", "initials": "SH"}, {"family": "Bentley", "given": "Kirsty", "initials": "K"}, {"family": "Wallner", "given": "Olov", "initials": "O"}, {"family": "Homan", "given": "Evert J", "initials": "EJ"}, {"family": "Scobie", "given": "Martin", "initials": "M"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}, {"family": "Prejan\u00f2", "given": "Mario", "initials": "M", "orcid": "0000-0002-9140-6246", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3149d1c394e5447b873012134ed902ac.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}, {"family": "de Vega", "given": "Miguel", "initials": "M", "orcid": "0000-0003-1285-7549", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6196fa790b4645c3acef45a87cdac3d0.json"}}, {"family": "Watson", "given": "Allan J B", "initials": "AJB", "orcid": "0000-0002-1582-4286", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/991264ae319e4e95a51e0b47b995c66e.json"}}, {"family": "Michel", "given": "Maurice", "initials": "M"}], "type": "journal article", "published": "2025-11-13", "journal": {"title": "J Med Chem", "issn": "1520-4804", "volume": "68", "issue": "21", "pages": "22455-22483", "issn-l": "0022-2623"}, "abstract": "The base excision repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1) plays a central role in maintaining genome integrity and mediating cellular responses to oxidative stress. As such, it represents an attractive target for pharmaceutical modulation. Small-molecule organocatalytic switches (ORCAs) greatly enhance the rate of OGG1-catalyzed cleavage of DNA abasic sites, thereby accelerating DNA repair. Here, we present the discovery and hit-to-lead optimization of a novel class of highly potent serotonin-derived ORCAs with greatly improved pharmacokinetic properties. Biochemical assays, X-ray crystallography, and molecular dynamics simulations point toward a water-mediated mechanism of activation, distinct from previously proposed Br\u00f8nsted base-assisted models. These findings establish serotonin-based ORCAs as promising chemical probes and potential leads for therapeutic modulation of OGG1 in oxidative stress-driven diseases.", "doi": "10.1021/acs.jmedchem.5c01454", "pmid": "41092057", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12621200"}], "notes": [], "created": "2026-08-20T08:10:54.321Z", "modified": "2026-08-20T08:10:54.746Z"}, {"entity": "publication", "iuid": "140cd67bdbfe479ab8cbcd20eaeca0ea", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/140cd67bdbfe479ab8cbcd20eaeca0ea.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/140cd67bdbfe479ab8cbcd20eaeca0ea"}}, "title": "The anabolic steroid stanozolol is a potent inhibitor of human MutT homolog 1.", "authors": [{"family": "Scaletti Hutchinson", "given": "Emma", "initials": "E"}, {"family": "Gustafsson Westergren", "given": "Robert", "initials": "R"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS"}, {"family": "Scobie", "given": "Martin", "initials": "M"}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}], "type": "journal article", "published": "2025-10-00", "journal": {"title": "FEBS Lett.", "issn": "1873-3468", "volume": "599", "issue": "19", "pages": "2790-2801", "issn-l": "0014-5793"}, "abstract": "Human MutT homolog 1 (hMTH1) removes damaged nucleotides from the nucleotide pool, preventing their incorporation into DNA. Due to its potential as an anticancer drug target, hMTH1 has been the focus of several inhibitor development studies. Unexpectedly, we show that the anabolic steroid stanozolol (Stz) is a potent nanomolar inhibitor of hMTH1. We present the structure of hMTH1 in complex with Stz, which indicates a unique core scaffold that could be exploited for future inhibitor development. Comparison with human protein structures bound with dihydrotestosterone (DHT) shows hMTH1 is entirely unrelated in terms of its structure. As these DHT binding proteins are all involved in steroid regulation, this makes the identification of Stz as a potent hMTH1 inhibitor all the more unusual.", "doi": "10.1002/1873-3468.70116", "pmid": "40878820", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12519060"}], "notes": [], "created": "2026-08-20T06:25:27.525Z", "modified": "2026-08-20T06:25:27.657Z"}, {"entity": "publication", "iuid": "b28fc4cc0e8a4eaca57d651057592f0b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b28fc4cc0e8a4eaca57d651057592f0b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b28fc4cc0e8a4eaca57d651057592f0b"}}, "title": "Kinetic and structural characterization of NUDT15 and NUDT18 as catalysts of isoprene pyrophosphate hydrolysis.", "authors": [{"family": "Scaletti", "given": "Emma R", "initials": "ER"}, {"family": "Unterlass", "given": "Judith E", "initials": "JE"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Vallin", "given": "Karl S", "initials": "KS"}, {"family": "Kapsitidou", "given": "Despina", "initials": "D"}, {"family": "Tsuber", "given": "Viktoriia", "initials": "V"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51f26d370fb74994b8e2b4fa1c9c2f7a.json"}}], "type": "journal article", "published": "2024-10-00", "journal": {"title": "FEBS J.", "issn": "1742-4658", "volume": "291", "issue": "19", "pages": "4301-4322", "issn-l": "1742-464X"}, "abstract": "Isoprene pyrophosphates play a crucial role in the synthesis of a diverse array of essential nonsterol and sterol biomolecules and serve as substrates for posttranslational isoprenylation of proteins, enabling specific anchoring to cellular membranes. Hydrolysis of isoprene pyrophosphates would be a means to modulate their levels, downstream products, and protein isoprenylation. While NUDIX hydrolases from plants have been described to catalyze the hydrolysis of isoprene pyrophosphates, homologous enzymes with this function in animals have not yet been reported. In this study, we screened an extensive panel of human NUDIX hydrolases for activity in hydrolyzing isoprene pyrophosphates. We found that human nucleotide triphosphate diphosphatase NUDT15 and 8-oxo-dGDP phosphatase NUDT18 efficiently catalyze the hydrolysis of several physiologically relevant isoprene pyrophosphates. Notably, we demonstrate that geranyl pyrophosphate is an excellent substrate for NUDT18, with a catalytic efficiency of 2.1 \u00d7 105 m-1\u00b7s-1, thus making it the best substrate identified for NUDT18 to date. Similarly, geranyl pyrophosphate proved to be the best isoprene pyrophosphate substrate for NUDT15, with a catalytic efficiency of 4.0 \u00d7 104 M-1\u00b7s-1. LC-MS analysis of NUDT15 and NUDT18 catalyzed isoprene pyrophosphate hydrolysis revealed the generation of the corresponding monophosphates and inorganic phosphate. Furthermore, we solved the crystal structure of NUDT15 in complex with the hydrolysis product geranyl phosphate at a resolution of 1.70 \u00c5. This structure revealed that the active site nicely accommodates the hydrophobic isoprenoid moiety and helped identify key binding residues. Our findings imply that isoprene pyrophosphates are endogenous substrates of NUDT15 and NUDT18, suggesting they are involved in animal isoprene pyrophosphate metabolism.", "doi": "10.1111/febs.17202", "pmid": "38944687", "labels": [], "xrefs": [{"db": "RefSeq", "key": "XP_003984764.1"}], "notes": [], "created": "2026-08-20T11:18:05.835Z", "modified": "2026-08-20T11:18:05.916Z"}, {"entity": "publication", "iuid": "0902e5b11ab54a689ca71a5f9c6a0c31", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0902e5b11ab54a689ca71a5f9c6a0c31.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0902e5b11ab54a689ca71a5f9c6a0c31"}}, "title": "Bacterial transcriptional repressor NrdR \u2013 a flexible multifactorial nucleotide sensor", "authors": [{"family": "Rozman Grinberg", "given": "Inna", "initials": "I", "orcid": "0000-0003-3094-1998", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fcae87675b4b421099e3ca26f5b321f1.json"}}, {"family": "Bima\u00ef", "given": "Ornella", "initials": "O", "orcid": "0000-0003-0562-7251", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d6c0d299f3434311a43e77fbb764975a.json"}}, {"family": "Shahid", "given": "Saher", "initials": "S", "orcid": "0000-0003-4107-8069", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/358e4cd11b3644ad92107c4152ff9e96.json"}}, {"family": "Philipp", "given": "Lena", "initials": "L"}, {"family": "Mart\u00ednez-Carranza", "given": "Markel", "initials": "M", "orcid": "0000-0003-0192-9762", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c5bc72614c24441788f53beac24df48a.json"}}, {"family": "Banerjee", "given": "Ipsita", "initials": "I"}, {"family": "Lundin", "given": "Daniel", "initials": "D", "orcid": "0000-0002-8779-6464", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/290a3bc9eb554620906b93d7f1d57184.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}, {"family": "Sj\u00f6berg", "given": "Britt Marie", "initials": "BM", "orcid": "0000-0001-5953-3360", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c6b66e4a9c374090bd55d5a302e98065.json"}}, {"family": "Logan", "given": "Derek T", "initials": "DT", "orcid": "0000-0002-0098-8560", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/64e6e27f8c8f470e9b390575d3bdbf17.json"}}], "type": "posted-content", "published": "2024-09-08", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2024.09.04.609659", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T10:58:19.348Z", "modified": "2026-08-20T10:58:19.595Z"}, {"entity": "publication", "iuid": "77475c1df233406b93598c917df16eeb", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/77475c1df233406b93598c917df16eeb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/77475c1df233406b93598c917df16eeb"}}, "title": "Kinetic and structural characterization of human NUDIX hydrolases NUDT15 and NUDT18 as catalysts of isoprene pyrophosphate hydrolysis", "authors": [{"family": "Scaletti", "given": "Emma R", "initials": "ER", "orcid": "0000-0002-8741-8981", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/77be7f5d51564a75a753579e976c7c72.json"}}, {"family": "Unterlass", "given": "Judith E", "initials": "JE", "orcid": "0000-0002-7504-8338", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0aa7804a71ab4293aca5a78554737016.json"}}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Vallin", "given": "Karl S", "initials": "KS"}, {"family": "Kapsitidou", "given": "Despina", "initials": "D"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}, {"family": "Jemth", "given": "Ann Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51f26d370fb74994b8e2b4fa1c9c2f7a.json"}}], "type": "posted-content", "published": "2023-11-29", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2023.11.29.569174", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T10:50:34.757Z", "modified": "2026-08-20T10:50:34.875Z"}, {"entity": "publication", "iuid": "ad59b1b98d8c42d881dd45a6ac12c52a", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ad59b1b98d8c42d881dd45a6ac12c52a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ad59b1b98d8c42d881dd45a6ac12c52a"}}, "title": "Coupling cellular drug-target engagement to downstream pharmacology with CeTEAM", "authors": [{"family": "Valerie", "given": "Nicholas C K", "initials": "NCK", "orcid": "0000-0002-9423-964X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/48bb9c8ab8a5465a8a4da1997f1af56d.json"}}, {"family": "Sanjiv", "given": "Kumar", "initials": "K", "orcid": "0000-0002-5415-9952", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f96227a0cfd8467ca6e8ac1146dda00a.json"}}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O", "orcid": "0000-0002-4290-4994", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f546fe8f2c54824b942f7f88976e3bd.json"}}, {"family": "Zhang", "given": "Si Min", "initials": "SM", "orcid": "0000-0001-7763-603X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/755a7ac0bd8c4e869428927871cead93.json"}}, {"family": "Alam", "given": "Seher", "initials": "S", "orcid": "0000-0002-8494-832X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/38a0280842714f1f92e6b54f49dcb559.json"}}, {"family": "Pires", "given": "Maria J", "initials": "MJ"}, {"family": "Stigsdotter", "given": "Hannah", "initials": "H"}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Langelier", "given": "Marie France", "initials": "MF", "orcid": "0000-0001-9815-1840", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/79beb7ce9d3b46528f35b1cf9038cf65.json"}}, {"family": "Rehling", "given": "Daniel", "initials": "D", "orcid": "0000-0002-8627-3469", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5aff0e51eb124b7183a9e752256288a4.json"}}, {"family": "Throup", "given": "Adam", "initials": "A", "orcid": "0000-0001-6512-8679", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1d7373aaa685464492b615ea4152b843.json"}}, {"family": "Desroses", "given": "Matthieu", "initials": "M", "orcid": "0000-0003-4152-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b251e222615747a7822bf3cc26749cde.json"}}, {"family": "Onireti", "given": "Jacob", "initials": "J"}, {"family": "Wakchaure", "given": "Prasad", "initials": "P", "orcid": "0000-0003-2828-4642", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4d20f3f040894567b699c50b8b9e9fd4.json"}}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Bostr\u00f6m", "given": "Johan", "initials": "J", "orcid": "0000-0001-5252-4023", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6e6b3b2450f0498f9d0be4d9af615e89.json"}}, {"family": "Bevc", "given": "Luka", "initials": "L"}, {"family": "Benzi", "given": "Giorgia", "initials": "G"}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}, {"family": "Pascal", "given": "John M", "initials": "JM", "orcid": "0000-0002-2714-4317", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/82a900bd9df84da594641911c65750f1.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}, {"family": "Page", "given": "Brent D G", "initials": "BDG", "orcid": "0000-0002-2101-1329", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6cb0faad98c34cf7b9d4f60d03274727.json"}}, {"family": "Altun", "given": "Mikael", "initials": "M", "orcid": "0000-0002-6937-6124", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d77b74fe6e7d44f4800fe8bb4404ad8f.json"}}], "type": "posted-content", "published": "2022-09-19", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2022.09.19.505646", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T10:14:18.579Z", "modified": "2026-08-20T10:14:19.029Z"}, {"entity": "publication", "iuid": "69a3ee484c8d4ce5aef327a1cef6b239", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/69a3ee484c8d4ce5aef327a1cef6b239.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/69a3ee484c8d4ce5aef327a1cef6b239"}}, "title": "Front Cover: The First Structure of Human MTHFD2L and Its Implications for the Development of Isoform\u2010Selective Inhibitors (ChemMedChem 18/2022)", "authors": [{"family": "Scaletti", "given": "Emma R", "initials": "ER"}, {"family": "Gustafsson Westergren", "given": "Robert", "initials": "R"}, {"family": "Andersson", "given": "Yasmin", "initials": "Y"}, {"family": "Wiita", "given": "Elisee", "initials": "E"}, {"family": "Henriksson", "given": "Martin", "initials": "M"}, {"family": "Homan", "given": "Evert J", "initials": "EJ"}, {"family": "Jemth", "given": "Ann\u2010Sofie", "initials": "A"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}], "type": "journal-article", "published": "2022-09-16", "journal": {"title": "ChemMedChem", "issn": "1860-7179", "volume": "17", "issue": "18", "issn-l": null}, "abstract": null, "doi": "10.1002/cmdc.202200478", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T06:31:24.526Z", "modified": "2026-08-20T06:31:24.596Z"}, {"entity": "publication", "iuid": "aecd36c8899d44f9b64d1e239c6cd3b9", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/aecd36c8899d44f9b64d1e239c6cd3b9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/aecd36c8899d44f9b64d1e239c6cd3b9"}}, "title": "The First Structure of Human MTHFD2L and Its Implications for the Development of Isoform-Selective Inhibitors.", "authors": [{"family": "Scaletti", "given": "Emma R", "initials": "ER"}, {"family": "Gustafsson Westergren", "given": "Robert", "initials": "R"}, {"family": "Andersson", "given": "Yasmin", "initials": "Y"}, {"family": "Wiita", "given": "Elisee", "initials": "E"}, {"family": "Henriksson", "given": "Martin", "initials": "M"}, {"family": "Homan", "given": "Evert J", "initials": "EJ"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}], "type": "journal article", "published": "2022-09-16", "journal": {"title": "ChemMedChem", "issn": "1860-7187", "volume": "17", "issue": "18", "pages": "e202200274", "issn-l": "1860-7179"}, "abstract": "Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a mitochondrial 1-carbon metabolism enzyme, which is an attractive anticancer drug target as it is highly upregulated in cancer but is not expressed in healthy adult cells. Selective MTHFD2 inhibitors could therefore offer reduced side-effects during treatment, which are common with antifolate drugs that target other 1C-metabolism enzymes. This task is challenging however, as MTHFD2 shares high sequence identity with the constitutively expressed isozymes cytosolic MTHFD1 and mitochondrial MTHFD2L. In fact, one of the most potent MTHFD2 inhibitors reported to date, TH7299, is actually more active against MTHFD1 and MTHFD2L. While structures of MTHFD2 and MTHFD1 exist, no MTHFD2L structures are available. We determined the first structure of MTHFD2L and its complex with TH7299, which reveals the structural basis for its highly potent MTHFD2L inhibition. Detailed analysis of the MTHFD2L structure presented here clearly highlights the challenges associated with developing truly isoform-selective MTHFD2 inhibitors.", "doi": "10.1002/cmdc.202200274", "pmid": "35712863", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9796130"}], "notes": [], "created": "2026-08-20T06:31:22.750Z", "modified": "2026-08-20T06:31:22.819Z"}, {"entity": "publication", "iuid": "5c5bfa7eea964cf7961bdec3453b5d92", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5c5bfa7eea964cf7961bdec3453b5d92.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5c5bfa7eea964cf7961bdec3453b5d92"}}, "title": "Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function.", "authors": [{"family": "Michel", "given": "Maurice", "initials": "M", "orcid": "0000-0003-3261-2493", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f4696e361fe4aa3823d263674d1a498.json"}}, {"family": "Ben\u00edtez-Buelga", "given": "Carlos", "initials": "C"}, {"family": "Calvo", "given": "Patricia A", "initials": "PA"}, {"family": "Hanna", "given": "Bishoy M F", "initials": "BMF", "orcid": "0000-0001-7027-6553", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/61301102836e44d189f5628bb33c1335.json"}}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O", "orcid": "0000-0002-4290-4994", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f546fe8f2c54824b942f7f88976e3bd.json"}}, {"family": "Masuyer", "given": "Geoffrey", "initials": "G", "orcid": "0000-0002-9527-2310", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c62ba219d3e34662aaa458dbd361cf31.json"}}, {"family": "Davies", "given": "Jonathan", "initials": "J", "orcid": "0000-0002-4986-8594", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e74e0781a72d480c8e705a9a824e5e5a.json"}}, {"family": "Wallner", "given": "Olov", "initials": "O", "orcid": "0000-0002-6481-237X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3601a5a4d88f4452b6d1ac5f22c79d9f.json"}}, {"family": "Sanjiv", "given": "Kumar", "initials": "K", "orcid": "0000-0002-5415-9952", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f96227a0cfd8467ca6e8ac1146dda00a.json"}}, {"family": "Albers", "given": "Julian J", "initials": "JJ", "orcid": "0000-0001-9579-6360", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8278cc4e9e7e4bde823f672b1982591d.json"}}, {"family": "Casta\u00f1eda-Zegarra", "given": "Sergio", "initials": "S", "orcid": "0000-0002-2808-6788", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3438015dbc1d41b797a02c25a37fef60.json"}}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51f26d370fb74994b8e2b4fa1c9c2f7a.json"}}, {"family": "Visnes", "given": "Torkild", "initials": "T", "orcid": "0000-0003-1047-988X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9fef10d6a8604971a6ad1849b9f8b029.json"}}, {"family": "Sastre-Perona", "given": "Ana", "initials": "A", "orcid": "0000-0002-4502-3025", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7d1f1df32dbd449c8f10a5ce0872a6b3.json"}}, {"family": "Danda", "given": "Akhilesh N", "initials": "AN"}, {"family": "Homan", "given": "Evert J", "initials": "EJ", "orcid": "0000-0002-9057-1848", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3a68aa16414c4c159c52a5e75d5537c1.json"}}, {"family": "Marimuthu", "given": "Karthick", "initials": "K"}, {"family": "Zhenjun", "given": "Zhao", "initials": "Z", "orcid": "0000-0003-1976-0790", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/019926f6c3d649ea9b04b7b37956dfda.json"}}, {"family": "Chi", "given": "Celestine N", "initials": "CN"}, {"family": "Sarno", "given": "Antonio", "initials": "A", "orcid": "0000-0002-9308-8018", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/22883e442f534ba99f2917cf45d95b3d.json"}}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "von Nicolai", "given": "Catharina", "initials": "C", "orcid": "0000-0002-7116-2635", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b6a7ea3d84de4bcb9366c5dcb5b36779.json"}}, {"family": "Komor", "given": "Anna J", "initials": "AJ", "orcid": "0000-0003-4806-4233", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5c3ee8bcb2ee41f1982b48bfed84b76f.json"}}, {"family": "Rajagopal", "given": "Varshni", "initials": "V"}, {"family": "M\u00fcller", "given": "Sarah", "initials": "S", "orcid": "0000-0002-9923-3298", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5012b873ff66448eb2e0ae2e284f7b5b.json"}}, {"family": "Hank", "given": "Emily C", "initials": "EC", "orcid": "0000-0002-3777-4697", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2b412977f2364bef9ec63aa5e552331a.json"}}, {"family": "Varga", "given": "Marek", "initials": "M", "orcid": "0000-0002-9685-8145", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/707532fc225c49d1b2d4f9bec632e13f.json"}}, {"family": "Scaletti", "given": "Emma R", "initials": "ER", "orcid": "0000-0002-8741-8981", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/77be7f5d51564a75a753579e976c7c72.json"}}, {"family": "Pandey", "given": "Monica", "initials": "M", "orcid": "0000-0002-5783-5995", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1d5af32166634f20b29a5f1ed9e12c43.json"}}, {"family": "Karsten", "given": "Stella", "initials": "S", "orcid": "0000-0001-6191-4314", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3a27ec21e4a34600aa24a7213372e19c.json"}}, {"family": "Haslene-Hox", "given": "Hanne", "initials": "H"}, {"family": "Loevenich", "given": "Simon", "initials": "S", "orcid": "0000-0001-5424-8755", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6a06b60008414ef09b0c1e360ae1d10f.json"}}, {"family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ed95784f80a45d9abb072fbb74fc225.json"}}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Mamonov", "given": "Kirill", "initials": "K", "orcid": "0000-0001-5971-4305", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2aeb36f9611f4c03883b8def30565da1.json"}}, {"family": "Ortis", "given": "Florian", "initials": "F", "orcid": "0000-0002-0458-5187", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a2e13b716bc349eb9dac083d7f801549.json"}}, {"family": "Sch\u00f6mberg", "given": "Fritz", "initials": "F", "orcid": "0000-0003-0092-0627", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7f10b06057e94d03a44967cce431c1a8.json"}}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Stewart", "given": "Josephine", "initials": "J"}, {"family": "D'Arcy-Evans", "given": "Nicholas", "initials": "N"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Henriksson", "given": "Martin", "initials": "M"}, {"family": "Michel", "given": "Dana", "initials": "D"}, {"family": "de Ory", "given": "Ana", "initials": "A"}, {"family": "Acero", "given": "Lucia", "initials": "L", "orcid": "0000-0001-8101-5412", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/af80832b8d8c4019bea17c15fa7651e2.json"}}, {"family": "Calvete", "given": "Oriol", "initials": "O", "orcid": "0000-0002-2623-2876", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0ee0251167344b24b97b971b8c750795.json"}}, {"family": "Scobie", "given": "Martin", "initials": "M", "orcid": "0000-0002-7073-8495", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bdce0df415d54e9d84a4fcbb4d1350e5.json"}}, {"family": "Hertweck", "given": "Christian", "initials": "C", "orcid": "0000-0002-0367-337X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2b1f3fa37a7d4378b06381c2e68a10cb.json"}}, {"family": "Vilotijevic", "given": "Ivan", "initials": "I", "orcid": "0000-0001-6199-0632", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/eec3fc0f230046ccbe7ff46b2da70792.json"}}, {"family": "Kalder\u00e9n", "given": "Christina", "initials": "C", "orcid": "0000-0001-7004-7048", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e9c7121a5e14414b8bace2708e8add2f.json"}}, {"family": "Osorio", "given": "Ana", "initials": "A", "orcid": "0000-0001-8124-3984", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6ecd4cc9c17d43009703efb95d979e09.json"}}, {"family": "Perona", "given": "Rosario", "initials": "R", "orcid": "0000-0002-2973-5153", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5b116837f5c346d49e70ad5eb28d7afb.json"}}, {"family": "Stolz", "given": "Alexandra", "initials": "A", "orcid": "0000-0002-3340-439X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4bde36f21953479a8762c1c858b4c451.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8b6cab92fb2c4597a0c04777095f80db.json"}}, {"family": "de Vega", "given": "Miguel", "initials": "M", "orcid": "0000-0003-1285-7549", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6196fa790b4645c3acef45a87cdac3d0.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}], "type": "journal article", "published": "2022-06-24", "journal": {"title": "Science (New York, N.Y.)", "issn": "1095-9203", "volume": "376", "issue": "6600", "pages": "1471-1476", "issn-l": "0036-8075"}, "abstract": "Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed \u03b2,\u03b4-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging.", "doi": "10.1126/science.abf8980", "pmid": "35737787", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:59:29.051Z", "modified": "2026-08-20T11:59:30.134Z"}, {"entity": "publication", "iuid": "85dfc86719fd4e699a0a07008f7b0f67", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/85dfc86719fd4e699a0a07008f7b0f67.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/85dfc86719fd4e699a0a07008f7b0f67"}}, "title": "Crystal structures of human PAICS reveal substrate and product binding of an emerging cancer target.", "authors": [{"family": "\u0160kerlov\u00e1", "given": "Jana", "initials": "J", "orcid": "0000-0002-9579-4047", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2981680ce6de48ca84cfee5f74a94f27.json"}}, {"family": "Unterlass", "given": "Judith", "initials": "J"}, {"family": "G\u00f6ttmann", "given": "Mona", "initials": "M"}, {"family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ed95784f80a45d9abb072fbb74fc225.json"}}, {"family": "Homan", "given": "Evert", "initials": "E"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51f26d370fb74994b8e2b4fa1c9c2f7a.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}], "type": "journal article", "published": "2020-08-14", "journal": {"title": "J Biol Chem", "issn": "1083-351X", "volume": "295", "issue": "33", "pages": "11656-11668", "issn-l": "0021-9258"}, "abstract": "The bifunctional human enzyme phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthetase (PAICS) catalyzes two essential steps in the de novo purine biosynthesis pathway. PAICS is overexpressed in many cancers and could be a promising target for the development of cancer therapeutics. Here, using gene knockdowns and clonogenic survival and cell viability assays, we demonstrate that PAICS is required for growth and survival of prostate cancer cells. PAICS catalyzes the carboxylation of aminoimidazole ribonucleotide (AIR) and the subsequent conversion of carboxyaminoimidazole ribonucleotide (CAIR) and l-aspartate to N-succinylcarboxamide-5-aminoimidazole ribonucleotide (SAICAR). Of note, we present the first structures of human octameric PAICS in complexes with native ligands. In particular, we report the structure of PAICS with CAIR bound in the active sites of both domains and SAICAR bound in one of the SAICAR synthetase domains. Moreover, we report the PAICS structure with SAICAR and an ATP analog occupying the SAICAR synthetase active site. These structures provide insight into substrate and product binding and the architecture of the active sites, disclosing important structural information for rational design of PAICS inhibitors as potential anticancer drugs.", "doi": "10.1074/jbc.RA120.013695", "pmid": "32571877", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7450103"}, {"db": "pii", "key": "S0021-9258(17)48465-1"}, {"db": "PDB", "key": "5clj"}, {"db": "PDB", "key": "2h31"}, {"db": "PDB", "key": "4ja0"}, {"db": "PDB", "key": "3rgg"}, {"db": "PDB", "key": "2nsl"}, {"db": "PDB", "key": "2gqs"}, {"db": "PDB", "key": "4fe2"}, {"db": "PDB", "key": "4o7w"}, {"db": "PDB", "key": "2z02"}, {"db": "PDB", "key": "2cnv"}, {"db": "PDB", "key": "2cnu"}, {"db": "PDB", "key": "1obd"}], "notes": [], "created": "2026-08-20T09:32:23.628Z", "modified": "2026-08-20T09:32:23.752Z"}, {"entity": "publication", "iuid": "e8c5934c61524c688421a2e4b3dd5c20", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e8c5934c61524c688421a2e4b3dd5c20.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e8c5934c61524c688421a2e4b3dd5c20"}}, "title": "MutT homologue 1 (MTH1) removes N6-methyl-dATP from the dNTP pool.", "authors": [{"family": "Scaletti", "given": "Emma Rose", "initials": "ER"}, {"family": "Vallin", "given": "Karl S", "initials": "KS"}, {"family": "Br\u00e4utigam", "given": "Lars", "initials": "L"}, {"family": "Sarno", "given": "Antonio", "initials": "A", "orcid": "0000-0002-9308-8018", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/22883e442f534ba99f2917cf45d95b3d.json"}}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51f26d370fb74994b8e2b4fa1c9c2f7a.json"}}], "type": "journal article", "published": "2020-04-10", "journal": {"title": "J Biol Chem", "issn": "1083-351X", "volume": "295", "issue": "15", "pages": "4761-4772", "issn-l": "0021-9258"}, "abstract": "MutT homologue 1 (MTH1) removes oxidized nucleotides from the nucleotide pool and thereby prevents their incorporation into the genome and thereby reduces genotoxicity. We previously reported that MTH1 is an efficient catalyst of O6-methyl-dGTP hydrolysis suggesting that MTH1 may also sanitize the nucleotide pool from other methylated nucleotides. We here show that MTH1 efficiently catalyzes the hydrolysis of N6-methyl-dATP to N6-methyl-dAMP and further report that N6-methylation of dATP drastically increases the MTH1 activity. We also observed MTH1 activity with N6-methyl-ATP, albeit at a lower level. We show that N6-methyl-dATP is incorporated into DNA in vivo, as indicated by increased N6-methyl-dA DNA levels in embryos developed from MTH1 knock-out zebrafish eggs microinjected with N6-methyl-dATP compared with noninjected embryos. N6-methyl-dATP activity is present in MTH1 homologues from distantly related vertebrates, suggesting evolutionary conservation and indicating that this activity is important. Of note, N6-methyl-dATP activity is unique to MTH1 among related NUDIX hydrolases. Moreover, we present the structure of N6-methyl-dAMP-bound human MTH1, revealing that the N6-methyl group is accommodated within a hydrophobic active-site subpocket explaining why N6-methyl-dATP is a good MTH1 substrate. N6-methylation of DNA and RNA has been reported to have epigenetic roles and to affect mRNA metabolism. We propose that MTH1 acts in concert with adenosine deaminase-like protein isoform 1 (ADAL1) to prevent incorporation of N6-methyl-(d)ATP into DNA and RNA. This would hinder potential dysregulation of epigenetic control and RNA metabolism via conversion of N6-methyl-(d)ATP to N6-methyl-(d)AMP, followed by ADAL1-catalyzed deamination producing (d)IMP that can enter the nucleotide salvage pathway.", "doi": "10.1074/jbc.RA120.012636", "pmid": "32144205", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7152754"}, {"db": "pii", "key": "S0021-9258(17)48573-5"}, {"db": "PDB", "key": "3ZR1"}, {"db": "PDB", "key": "3ZR0"}, {"db": "PDB", "key": "5OTM"}, {"db": "PDB", "key": "6QVO"}, {"db": "PDB", "key": "5OTN"}, {"db": "PDB", "key": "6FL4"}, {"db": "PDB", "key": "3A6T"}], "notes": [], "created": "2026-08-20T09:32:21.804Z", "modified": "2026-08-20T09:32:21.945Z"}, {"entity": "publication", "iuid": "9ab5835c732a4b7d97d4b021c093454b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/9ab5835c732a4b7d97d4b021c093454b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/9ab5835c732a4b7d97d4b021c093454b"}}, "title": "Structural basis for the interaction of the chaperone Cbp3 with newly synthesized cytochrome b during mitochondrial respiratory chain assembly.", "authors": [{"family": "Ndi", "given": "Mama", "initials": "M"}, {"family": "Masuyer", "given": "Geoffrey", "initials": "G", "orcid": "0000-0002-9527-2310", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c62ba219d3e34662aaa458dbd361cf31.json"}}, {"family": "Dawitz", "given": "Hannah", "initials": "H"}, {"family": "Carlstr\u00f6m", "given": "Andreas", "initials": "A"}, {"family": "Michel", "given": "Mirco", "initials": "M"}, {"family": "Elofsson", "given": "Arne", "initials": "A"}, {"family": "Rapp", "given": "Mikaela", "initials": "M"}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}, {"family": "Ott", "given": "Martin", "initials": "M", "orcid": "0000-0001-6367-3091", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3a4e515dde6d415cb0b0b4877cc7207a.json"}}], "type": "journal article", "published": "2019-11-08", "journal": {"title": "J Biol Chem", "issn": "1083-351X", "volume": "294", "issue": "45", "pages": "16663-16671", "issn-l": "0021-9258"}, "abstract": "Assembly of the mitochondrial respiratory chain requires the coordinated synthesis of mitochondrial and nuclear encoded subunits, redox co-factor acquisition, and correct joining of the subunits to form functional complexes. The conserved Cbp3-Cbp6 chaperone complex binds newly synthesized cytochrome b and supports the ordered acquisition of the heme co-factors. Moreover, it functions as a translational activator by interacting with the mitoribosome. Cbp3 consists of two distinct domains: an N-terminal domain present in mitochondrial Cbp3 homologs and a highly conserved C-terminal domain comprising a ubiquinol-cytochrome c chaperone region. Here, we solved the crystal structure of this C-terminal domain from a bacterial homolog at 1.4 \u00c5 resolution, revealing a unique all-helical fold. This structure allowed mapping of the interaction sites of yeast Cbp3 with Cbp6 and cytochrome b via site-specific photo-cross-linking. We propose that mitochondrial Cbp3 homologs carry an N-terminal extension that positions the conserved C-terminal domain at the ribosomal tunnel exit for an efficient interaction with its substrate, the newly synthesized cytochrome b protein.", "doi": "10.1074/jbc.RA119.010483", "pmid": "31537648", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6851329"}, {"db": "pii", "key": "S0021-9258(20)30513-5"}, {"db": "PDB", "key": "6GIQ"}, {"db": "PDB", "key": "5MRC"}, {"db": "PDB", "key": "6RWT"}], "notes": [], "created": "2026-08-20T09:32:17.818Z", "modified": "2026-08-20T09:32:17.966Z"}]}