{"entity": "researcher", "timestamp": "2026-06-15T17:51:06.237Z", "family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "affiliations": ["Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/2e3e92bdf843456784f98d3b521d2ccd.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/2e3e92bdf843456784f98d3b521d2ccd"}}, "publications": [{"entity": "publication", "iuid": "12f24de0714c4426bd445a0e28fb18c0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/12f24de0714c4426bd445a0e28fb18c0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/12f24de0714c4426bd445a0e28fb18c0"}}, "title": "Formate overflow drives toxic folate trapping in MTHFD1 inhibited cancer cells.", "authors": [{"family": "Green", "given": "Alanna C", "initials": "AC", "orcid": "0000-0002-0175-1485", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3c3193266a24fafb796e21b0a95c6cb.json"}}, {"family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e3e92bdf843456784f98d3b521d2ccd.json"}}, {"family": "Kiweler", "given": "Nicole", "initials": "N", "orcid": "0000-0001-7493-703X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8b0eaee2d574b4daba1ee735c512797.json"}}, {"family": "Chalkiadaki", "given": "Christina", "initials": "C"}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "Cookson", "given": "Victoria", "initials": "V"}, {"family": "Lesur", "given": "Antoine", "initials": "A"}, {"family": "Eiden", "given": "Kim", "initials": "K"}, {"family": "Bernardin", "given": "Fran\u00e7ois", "initials": "F", "orcid": "0000-0002-6329-5542", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc67be6d569140d3afa6d923a7b85e9d.json"}}, {"family": "Vallin", "given": "Karl S A", "initials": "KSA"}, {"family": "Borhade", "given": "Sanjay", "initials": "S"}, {"family": "Long", "given": "Maeve", "initials": "M"}, {"family": "Ghahe", "given": "Elahe Kamali", "initials": "EK"}, {"family": "Jim\u00e9nez-Alonso", "given": "Julio J", "initials": "JJ"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd07c6c543544af1a904e039f73ba857.json"}}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Mortusewicz", "given": "Oliver", "initials": "O", "orcid": "0000-0002-4290-4994", "researcher": {"href": "https://publications.scilifelab.se/researcher/b62a88fc39a54906a40e28e679c9f624.json"}}, {"family": "Meyers", "given": "Marianne", "initials": "M"}, {"family": "Viry", "given": "Elodie", "initials": "E"}, {"family": "Johansson", "given": "Annika I", "initials": "AI", "orcid": "0000-0001-5000-1288", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b0835b94db946929c1cb0c8f9319068.json"}}, {"family": "Hodek", "given": "Ond\u0159ej", "initials": "O", "orcid": "0000-0001-8307-9575", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e3bcef870804d4f9ec3d3e257cbc323.json"}}, {"family": "Homan", "given": "Evert", "initials": "E"}, {"family": "Bonagas", "given": "Nadilly", "initials": "N", "orcid": "0000-0001-7336-4065", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e38f3b0752740969c5c13fb77885b27.json"}}, {"family": "Ramos", "given": "Louise", "initials": "L", "orcid": "0000-0002-3808-6853", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe708067508a48eba89caed34f06be36.json"}}, {"family": "Sandberg", "given": "Lars", "initials": "L"}, {"family": "Fr\u00f6din", "given": "Morten", "initials": "M"}, {"family": "Moussay", "given": "Etienne", "initials": "E", "orcid": "0000-0002-0879-8067", "researcher": {"href": "https://publications.scilifelab.se/researcher/28965f7f1da94e969c5e16ec594462e2.json"}}, {"family": "Slipicevic", "given": "Ana", "initials": "A"}, {"family": "Letellier", "given": "Elisabeth", "initials": "E", "orcid": "0000-0001-8242-9393", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc06ccab76e24f2d88755bb90b713423.json"}}, {"family": "Paggetti", "given": "J\u00e9r\u00f4me", "initials": "J", "orcid": "0000-0001-9460-5876", "researcher": {"href": "https://publications.scilifelab.se/researcher/19962ab6e6974b35946c660a2c7551e5.json"}}, {"family": "S\u00f8rensen", "given": "Claus Storgaard", "initials": "CS"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Henriksson", "given": "Martin", "initials": "M", "orcid": "0000-0002-2230-4887", "researcher": {"href": "https://publications.scilifelab.se/researcher/8ad0e6d72bac4962805ba267db810a90.json"}}, {"family": "Meiser", "given": "Johannes", "initials": "J", "orcid": "0000-0002-9093-6210", "researcher": {"href": "https://publications.scilifelab.se/researcher/b83edb0c60e54fc9a26ddfb3165d069b.json"}}], "type": "journal article", "published": "2023-04-00", "journal": {"title": "Nat Metab", "issn": "2522-5812", "issn-l": "2522-5812", "volume": "5", "issue": "4", "pages": "642-659"}, "abstract": "Cancer cells fuel their increased need for nucleotide supply by upregulating one-carbon (1C) metabolism, including the enzymes methylenetetrahydrofolate dehydrogenase-cyclohydrolase 1 and 2 (MTHFD1 and MTHFD2). TH9619 is a potent inhibitor of dehydrogenase and cyclohydrolase activities in both MTHFD1 and MTHFD2, and selectively kills cancer cells. Here, we reveal that, in cells, TH9619 targets nuclear MTHFD2 but does not inhibit mitochondrial MTHFD2. Hence, overflow of formate from mitochondria continues in the presence of TH9619. TH9619 inhibits the activity of MTHFD1 occurring downstream of mitochondrial formate release, leading to the accumulation of 10-formyl-tetrahydrofolate, which we term a 'folate trap'. This results in thymidylate depletion and death of MTHFD2-expressing cancer cells. This previously uncharacterized folate trapping mechanism is exacerbated by physiological hypoxanthine levels that block the de novo purine synthesis pathway, and additionally prevent 10-formyl-tetrahydrofolate consumption for purine synthesis. The folate trapping mechanism described here for TH9619 differs from other MTHFD1/2 inhibitors and antifolates. Thus, our findings uncover an approach to attack cancer and reveal a regulatory mechanism in 1C metabolism.", "doi": "10.1038/s42255-023-00771-5", "pmid": "37012496", "labels": {"Swedish Metabolomics Centre": "Collaborative", "Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10132981"}, {"db": "pii", "key": "10.1038/s42255-023-00771-5"}], "notes": [], "created": "2023-08-30T07:09:03.400Z", "modified": "2025-10-17T13:05:07.625Z"}, {"entity": "publication", "iuid": "15722bb1086f44f7bd700d32703ab2a9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/15722bb1086f44f7bd700d32703ab2a9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/15722bb1086f44f7bd700d32703ab2a9"}}, "title": "Identification and evaluation of small-molecule inhibitors against the dNTPase SAMHD1viaa comprehensive screening funnel", "authors": [{"family": "Zhang", "given": "Si Min", "initials": "SM", "orcid": "0000-0001-7763-603X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1eac01c3a53d4940ade49b24f13dd214.json"}}, {"family": "Paulin", "given": "Cynthia B J", "initials": "CBJ", "orcid": "0000-0002-5698-7962", "researcher": {"href": "https://publications.scilifelab.se/researcher/f54dd3938c0640f1b770a3b52baba6d9.json"}}, {"family": "Michel", "given": "Maurice", "initials": "M", "orcid": "0000-0003-3261-2493", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f7cb5d695254481b745f86a824ac1b5.json"}}, {"family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e3e92bdf843456784f98d3b521d2ccd.json"}}, {"family": "Yag\u00fce-Capilla", "given": "Miriam", "initials": "M"}, {"family": "Bwanika", "given": "Henri Colyn", "initials": "HC"}, {"family": "Shu", "given": "Huazhang", "initials": "H"}, {"family": "Vekatram", "given": "Rajagopal Papagudi", "initials": "RP"}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "Jemth", "given": "Ann Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd07c6c543544af1a904e039f73ba857.json"}}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Ortis", "given": "Florian", "initials": "F"}, {"family": "Dirks", "given": "Christopher", "initials": "C", "orcid": "0000-0003-4503-8291", "researcher": {"href": "https://publications.scilifelab.se/researcher/2188fde32a784feaa40cfff1e18c1125.json"}}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Linde", "given": "Erika", "initials": "E"}, {"family": "Lee", "given": "Sun", "initials": "S"}, {"family": "Llona-Minguez", "given": "Sabin", "initials": "S", "orcid": "0000-0003-3187-722X", "researcher": {"href": "https://publications.scilifelab.se/researcher/437b1f98ad21471f884226ed89a3da12.json"}}, {"family": "Haraldsson", "given": "Martin", "initials": "M", "orcid": "0000-0003-0743-7830", "researcher": {"href": "https://publications.scilifelab.se/researcher/42031e3e48ba47f896b74bfb733cdeff.json"}}, {"family": "Str\u00f6mberg", "given": "Kia", "initials": "K"}, {"family": "Homan", "given": "Evert J", "initials": "EJ"}, {"family": "Scobie", "given": "Martin", "initials": "M", "orcid": "0000-0002-7073-8495", "researcher": {"href": "https://publications.scilifelab.se/researcher/87c041a8b3414f5db02873dc8013806b.json"}}, {"family": "Lundb\u00e4ck", "given": "Thomas", "initials": "T", "orcid": "0000-0002-8145-7808", "researcher": {"href": "https://publications.scilifelab.se/researcher/e13df787cb884549bcf333aba4e6f010.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf1e23d9748e4868a4b5e966e423b1a9.json"}}], "type": "posted-content", "published": "2023-01-18", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2023.01.17.524275", "pmid": null, "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [], "notes": [], "created": "2023-10-18T18:41:03.768Z", "modified": "2025-12-18T19:56:49.749Z"}, {"entity": "publication", "iuid": "483fd25be0c940a88ec33ee37fd176c8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/483fd25be0c940a88ec33ee37fd176c8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/483fd25be0c940a88ec33ee37fd176c8"}}, "title": "Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress.", "authors": [{"family": "Bonagas", "given": "Nadilly", "initials": "N", "orcid": "0000-0001-7336-4065", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e38f3b0752740969c5c13fb77885b27.json"}}, {"family": "Gustafsson", "given": "Nina M S", "initials": "NMS"}, {"family": "Henriksson", "given": "Martin", "initials": "M"}, {"family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e3e92bdf843456784f98d3b521d2ccd.json"}}, {"family": "Gustafsson", "given": "Robert", "initials": "R", "orcid": "0000-0002-4854-5531", "researcher": {"href": "https://publications.scilifelab.se/researcher/16dd7e73adad4f85972d1d546bfa6d2a.json"}}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "Borhade", "given": "Sanjay", "initials": "S"}, {"family": "Green", "given": "Alanna C", "initials": "AC"}, {"family": "Vallin", "given": "Karl S A", "initials": "KSA"}, {"family": "Sarno", "given": "Antonio", "initials": "A"}, {"family": "Svensson", "given": "Richard", "initials": "R"}, {"family": "G\u00f6kt\u00fcrk", "given": "Camilla", "initials": "C"}, {"family": "Pham", "given": "Therese", "initials": "T"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd07c6c543544af1a904e039f73ba857.json"}}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Cookson", "given": "Victoria", "initials": "V", "orcid": "0000-0003-3089-4837", "researcher": {"href": "https://publications.scilifelab.se/researcher/3cd81b473de74c26bad811b3c2f25b7f.json"}}, {"family": "Kiweler", "given": "Nicole", "initials": "N", "orcid": "0000-0001-7493-703X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8b0eaee2d574b4daba1ee735c512797.json"}}, {"family": "Sandberg", "given": "Lars", "initials": "L"}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "Unterlass", "given": "Judith E", "initials": "JE"}, {"family": "Haraldsson", "given": "Martin", "initials": "M"}, {"family": "Andersson", "given": "Yasmin", "initials": "Y"}, {"family": "Scaletti", "given": "Emma R", "initials": "ER"}, {"family": "Bengtsson", "given": "Christoffer", "initials": "C"}, {"family": "Paulin", "given": "Cynthia B J", "initials": "CBJ"}, {"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Abdurakhmanov", "given": "Eldar", "initials": "E"}, {"family": "Pudelko", "given": "Linda", "initials": "L"}, {"family": "Kunz", "given": "Ben", "initials": "B"}, {"family": "Desroses", "given": "Matthieu", "initials": "M"}, {"family": "Iliev", "given": "Petar", "initials": "P"}, {"family": "F\u00e4rneg\u00e5rdh", "given": "Katarina", "initials": "K"}, {"family": "Kr\u00e4mer", "given": "Andreas", "initials": "A", "orcid": "0000-0003-3294-2660", "researcher": {"href": "https://publications.scilifelab.se/researcher/37f158e9b24d43b69753ccbf029cb793.json"}}, {"family": "Garg", "given": "Neeraj", "initials": "N"}, {"family": "Michel", "given": "Maurice", "initials": "M"}, {"family": "H\u00e4ggblad", "given": "Sara", "initials": "S"}, {"family": "Jarvius", "given": "Malin", "initials": "M"}, {"family": "Kalder\u00e9n", "given": "Christina", "initials": "C"}, {"family": "Jensen", "given": "Amanda B\u00f6gedahl", "initials": "AB"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Karsten", "given": "Stella", "initials": "S", "orcid": "0000-0001-6191-4314", "researcher": {"href": "https://publications.scilifelab.se/researcher/4cbde9247c7145ff8ea0bbc0b0c5c477.json"}}, {"family": "Zhang", "given": "Si Min", "initials": "SM"}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M"}, {"family": "Eriksson", "given": "Anders", "initials": "A"}, {"family": "Liu", "given": "Jianping", "initials": "J", "orcid": "0000-0002-7336-3895", "researcher": {"href": "https://publications.scilifelab.se/researcher/e77624d9d5b841608e142afbe2ead1d7.json"}}, {"family": "Glinghammar", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Nekhotiaeva", "given": "Natalia", "initials": "N"}, {"family": "Klingeg\u00e5rd", "given": "Fredrik", "initials": "F"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Martens", "given": "Ulf", "initials": "U"}, {"family": "Llona-Minguez", "given": "Sabin", "initials": "S"}, {"family": "Moulson", "given": "Ruth", "initials": "R"}, {"family": "Nordstr\u00f6m", "given": "Helena", "initials": "H"}, {"family": "Parrow", "given": "Vendela", "initials": "V"}, {"family": "Dahllund", "given": "Leif", "initials": "L"}, {"family": "Sj\u00f6berg", "given": "Birger", "initials": "B"}, {"family": "Vargas", "given": "Irene L", "initials": "IL"}, {"family": "Vo", "given": "Duy Duc", "initials": "DD"}, {"family": "Wannberg", "given": "Johan", "initials": "J", "orcid": "0000-0001-5494-0848", "researcher": {"href": "https://publications.scilifelab.se/researcher/d093f5fb52f644ce8994f3a6308272a8.json"}}, {"family": "Knapp", "given": "Stefan", "initials": "S", "orcid": "0000-0001-5995-6494", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4d84c40612d48f280d4ead25558d835.json"}}, {"family": "Krokan", "given": "Hans E", "initials": "HE"}, {"family": "Arvidsson", "given": "Per I", "initials": "PI", "orcid": "0000-0002-9453-6812", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae064b90b750457e80e974947f2dfc7a.json"}}, {"family": "Scobie", "given": "Martin", "initials": "M"}, {"family": "Meiser", "given": "Johannes", "initials": "J"}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.json"}}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW"}, {"family": "Homan", "given": "Evert J", "initials": "EJ"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}], "type": "journal article", "published": "2022-02-00", "journal": {"title": "Nat Cancer", "issn": "2662-1347", "volume": "3", "issue": "2", "pages": "156-172", "issn-l": null}, "abstract": "The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors.", "doi": "10.1038/s43018-022-00331-y", "pmid": "35228749", "labels": {"Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s43018-022-00331-y"}, {"db": "pmc", "key": "PMC8885417"}], "notes": [], "created": "2022-05-07T05:35:33.240Z", "modified": "2025-10-17T13:05:07.816Z"}, {"entity": "publication", "iuid": "911de50d46654337a749860d7a8635b1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/911de50d46654337a749860d7a8635b1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/911de50d46654337a749860d7a8635b1"}}, "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.scilifelab.se/researcher/cde5c1c6ccb94ca3be0b092771e67524.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.scilifelab.se/researcher/2e3e92bdf843456784f98d3b521d2ccd.json"}}, {"family": "Homan", "given": "Evert", "initials": "E"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd07c6c543544af1a904e039f73ba857.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.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": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pii", "key": "S0021-9258(17)48465-1"}, {"db": "pmc", "key": "PMC7450103"}, {"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": "2020-10-03T09:58:37.898Z", "modified": "2021-11-10T12:48:19.342Z"}]}