{"entity": "researcher", "timestamp": "2026-03-09T08:56:51.411Z", "family": "\u0160kerlov\u00e1", "given": "Jana", "initials": "J", "orcid": "0000-0002-9579-4047", "affiliations": ["Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/cde5c1c6ccb94ca3be0b092771e67524.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/cde5c1c6ccb94ca3be0b092771e67524"}}, "publications": [{"entity": "publication", "iuid": "1d08fde7b77e4bf5b87eac8ed9144e1c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1d08fde7b77e4bf5b87eac8ed9144e1c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1d08fde7b77e4bf5b87eac8ed9144e1c"}}, "title": "Activity of botulinum neurotoxin X and its structure when shielded by a non-toxic non-hemagglutinin protein.", "authors": [{"family": "Mart\u00ednez-Carranza", "given": "Markel", "initials": "M", "orcid": "0000-0003-0192-9762", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ad7db8205c847a5bf56843d600e5ce1.json"}}, {"family": "\u0160kerlov\u00e1", "given": "Jana", "initials": "J", "orcid": "0000-0002-9579-4047", "researcher": {"href": "https://publications.scilifelab.se/researcher/cde5c1c6ccb94ca3be0b092771e67524.json"}}, {"family": "Lee", "given": "Pyung-Gang", "initials": "PG"}, {"family": "Zhang", "given": "Jie", "initials": "J"}, {"family": "Kr\u010d", "given": "Ajda", "initials": "A", "orcid": "0009-0007-5842-8527", "researcher": {"href": "https://publications.scilifelab.se/researcher/cda5c360c20149279692c5d69df7a694.json"}}, {"family": "Sirohiwal", "given": "Abhishek", "initials": "A", "orcid": "0000-0002-4073-7627", "researcher": {"href": "https://publications.scilifelab.se/researcher/5171ae67d7bc4979908b2c12ecf1ce75.json"}}, {"family": "Burgin", "given": "Dave", "initials": "D"}, {"family": "Elliott", "given": "Mark", "initials": "M"}, {"family": "Philippe", "given": "Jules", "initials": "J"}, {"family": "Donald", "given": "Sarah", "initials": "S"}, {"family": "Hornby", "given": "Fraser", "initials": "F"}, {"family": "Henriksson", "given": "Linda", "initials": "L"}, {"family": "Masuyer", "given": "Geoffrey", "initials": "G", "orcid": "0000-0002-9527-2310", "researcher": {"href": "https://publications.scilifelab.se/researcher/41dcc0806dba4a56bb04725812f3a000.json"}}, {"family": "Kaila", "given": "Ville R I", "initials": "VRI", "orcid": "0000-0003-4464-6324", "researcher": {"href": "https://publications.scilifelab.se/researcher/cdcc63256cea406c9cb9cdaecc9cbcbe.json"}}, {"family": "Beard", "given": "Matthew", "initials": "M"}, {"family": "Dong", "given": "Min", "initials": "M", "orcid": "0000-0002-1744-7293", "researcher": {"href": "https://publications.scilifelab.se/researcher/30fd6ee44bfd4ae38eb733e19cbf338c.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": "2024-08-13", "journal": {"title": "Commun Chem", "issn": "2399-3669", "volume": "7", "issue": "1", "pages": "179", "issn-l": null}, "abstract": "Botulinum neurotoxins (BoNTs) are the most potent toxins known and are used to treat an increasing number of medical disorders. All BoNTs are naturally co-expressed with a protective partner protein (NTNH) with which they form a 300 kDa complex, to resist acidic and proteolytic attack from the digestive tract. We have previously identified a new botulinum neurotoxin serotype, BoNT/X, that has unique and therapeutically attractive properties. We present the cryo-EM structure of the BoNT/X-NTNH/X complex and the crystal structure of the isolated NTNH protein. Unexpectedly, the BoNT/X complex is stable and protease-resistant at both neutral and acidic pH and disassembles only in alkaline conditions. Using the stabilizing effect of NTNH, we isolated BoNT/X and showed that it has very low potency both in vitro and in vivo. Given the high catalytic activity and translocation efficacy of BoNT/X, low activity of the full toxin is likely due to the receptor-binding domain, which presents very weak ganglioside binding and exposed hydrophobic surfaces.", "doi": "10.1038/s42004-024-01262-8", "pmid": "39138288", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11322297"}, {"db": "pii", "key": "10.1038/s42004-024-01262-8"}], "notes": [], "created": "2024-11-15T13:45:47.397Z", "modified": "2025-10-25T10:17:13.297Z"}, {"entity": "publication", "iuid": "058fd5d30a614f4d938deb48ebf7b6fe", "links": {"self": {"href": "https://publications.scilifelab.se/publication/058fd5d30a614f4d938deb48ebf7b6fe.json"}, "display": {"href": "https://publications.scilifelab.se/publication/058fd5d30a614f4d938deb48ebf7b6fe"}}, "title": "The cryo-EM structure of the BoNT/Wo-NTNH complex reveals two immunoglobulin-like domains.", "authors": [{"family": "Ko\u0161enina", "given": "Sara", "initials": "S", "orcid": "0000-0001-7893-0249", "researcher": {"href": "https://publications.scilifelab.se/researcher/9370d4ecf19c438bb205c43c23f94f26.json"}}, {"family": "\u0160kerlov\u00e1", "given": "Jana", "initials": "J", "orcid": "0000-0002-9579-4047", "researcher": {"href": "https://publications.scilifelab.se/researcher/cde5c1c6ccb94ca3be0b092771e67524.json"}}, {"family": "Zhang", "given": "Sicai", "initials": "S"}, {"family": "Dong", "given": "Min", "initials": "M"}, {"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": "2024-02-00", "journal": {"title": "FEBS J.", "issn": "1742-4658", "volume": "291", "issue": "4", "pages": "676-689", "issn-l": "1742-464X"}, "abstract": "The botulinum neurotoxin-like toxin from Weissella oryzae (BoNT/Wo) is one of the BoNT-like toxins recently identified outside of the Clostridium genus. We show that, like the canonical BoNTs, BoNT/Wo forms a complex with its non-toxic non-hemagglutinin (NTNH) partner, which in traditional BoNT serotypes protects the toxin from proteases and the acidic environment of the hosts' guts. We here report the cryo-EM structure of the 300 kDa BoNT/Wo-NTNH/Wo complex together with pH stability studies of the complex. The structure reveals molecular details of the toxin's interactions with its protective partner. The overall structural arrangement is similar to other reported BoNT-NTNH complexes, but NTNH/Wo uniquely contains two extra bacterial immunoglobulin-like (Big) domains on the C-terminus. Although the function of these Big domains is unknown, they are structurally most similar to bacterial proteins involved in adhesion to host cells. In addition, the BoNT/Wo protease domain contains an internal disulfide bond not seen in other BoNTs. Mass photometry analysis revealed that the BoNT/Wo-NTNH/Wo complex is stable under acidic conditions and may dissociate at neutral to basic pH. These findings established that BoNT/Wo-NTNH/Wo shares the general fold of canonical BoNT-NTNH complexes. The presence of unique structural features suggests that it may have an alternative mode of activation, translocation and recognition of host cells, raising interesting questions about the activity and the mechanism of action of BoNT/Wo as well as about its target environment, receptors and substrates.", "doi": "10.1111/febs.16964", "pmid": "37746829", "labels": {"Cryo-EM": "Service"}, "xrefs": [], "notes": [], "created": "2023-11-28T13:03:49.085Z", "modified": "2025-10-25T10:17:41.448Z"}, {"entity": "publication", "iuid": "9efcb16d38144c20934369e886656d99", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9efcb16d38144c20934369e886656d99.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9efcb16d38144c20934369e886656d99"}}, "title": "Structure of the native pyruvate dehydrogenase complex reveals the mechanism of substrate insertion.", "authors": [{"family": "\u0160kerlov\u00e1", "given": "Jana", "initials": "J", "orcid": "0000-0002-9579-4047", "researcher": {"href": "https://publications.scilifelab.se/researcher/cde5c1c6ccb94ca3be0b092771e67524.json"}}, {"family": "Berndtsson", "given": "Jens", "initials": "J", "orcid": "0000-0001-6627-8134", "researcher": {"href": "https://publications.scilifelab.se/researcher/7620a5c7c0f245a28771d57d7179abbd.json"}}, {"family": "Nolte", "given": "Hendrik", "initials": "H"}, {"family": "Ott", "given": "Martin", "initials": "M", "orcid": "0000-0001-6367-3091", "researcher": {"href": "https://publications.scilifelab.se/researcher/b27b582dbd2a47bcbb0fb3194277902a.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": "2021-09-06", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "12", "issue": "1", "pages": "5277", "issn-l": "2041-1723"}, "abstract": "The pyruvate dehydrogenase complex (PDHc) links glycolysis to the citric acid cycle by converting pyruvate into acetyl-coenzyme A. PDHc encompasses three enzymatically active subunits, namely pyruvate dehydrogenase, dihydrolipoyl transacetylase, and dihydrolipoyl dehydrogenase. Dihydrolipoyl transacetylase is a multidomain protein comprising a varying number of lipoyl domains, a peripheral subunit-binding domain, and a catalytic domain. It forms the structural core of the complex, provides binding sites for the other enzymes, and shuffles reaction intermediates between the active sites through covalently bound lipoyl domains. The molecular mechanism by which this shuttling occurs has remained elusive. Here, we report a cryo-EM reconstruction of the native E. coli dihydrolipoyl transacetylase core in a resting state. This structure provides molecular details of the assembly of the core and reveals how the lipoyl domains interact with the core at the active site.", "doi": "10.1038/s41467-021-25570-y", "pmid": "34489474", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-021-25570-y"}, {"db": "pmc", "key": "PMC8421416"}], "notes": [], "created": "2021-09-07T14:15:11.241Z", "modified": "2021-11-10T12:22:09.547Z"}, {"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"}]}