{"entity": "researcher", "timestamp": "2026-08-20T20:37:08.365Z", "family": "Bj\u00f6rnstedt", "given": "Mikael", "initials": "M", "orcid": "0000-0003-2831-3837", "affiliations": ["Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, SE-141 86, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/08e79d991fab47c18b7390c7ddc12963.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/08e79d991fab47c18b7390c7ddc12963"}}, "publications": [{"entity": "publication", "iuid": "2108b46955d444a39235fed52f4243dc", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2108b46955d444a39235fed52f4243dc.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2108b46955d444a39235fed52f4243dc"}}, "title": "Mutational insights into human kynurenine aminotransferase 1: modulation of transamination and \u03b2-elimination activities across diverse substrates.", "authors": [{"family": "Selvam", "given": "Arun Kumar", "initials": "AK", "orcid": "0000-0002-9854-2048", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8e7a8d1d439a4ed0aebad8389a7253e2.json"}}, {"family": "Sun", "given": "Renhua", "initials": "R", "orcid": "0000-0002-8203-4946", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/29b44e08db3a4482a6a40bbda52fe815.json"}}, {"family": "Razaghi", "given": "Ali", "initials": "A", "orcid": "0000-0001-8771-998X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b978f17f56764dfb8fbef3fd06d10214.json"}}, {"family": "Salter", "given": "Hugh", "initials": "H", "orcid": "0000-0001-5705-2950", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c405a1c865d34a769095ada5edc8d04b.json"}}, {"family": "Sandalova", "given": "Tatiana", "initials": "T", "orcid": "0000-0002-7694-6420", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d2ea3d2ec9e94fe3876f88bd0786c24b.json"}}, {"family": "Bj\u00f6rnstedt", "given": "Mikael", "initials": "M", "orcid": "0000-0003-2831-3837", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/08e79d991fab47c18b7390c7ddc12963.json"}}, {"family": "Achour", "given": "Adnane", "initials": "A", "orcid": "0000-0003-0432-710X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/65fba324156a4fcbafbe636e642587a9.json"}}], "type": "journal article", "published": "2025-08-18", "journal": {"title": "Biochem. J.", "issn": "1470-8728", "volume": "482", "issue": "16", "pages": "1163-1180", "issn-l": "0264-6021"}, "abstract": "Human kynurenine aminotransferase 1 (hKYAT1) plays a crucial role in the transamination of aromatic amino acids and kynurenine. This promiscuous homodimeric enzyme transaminates various amino acids into their corresponding \u03b1-keto acids. Additionally, hKYAT1 is known to catalyze the \u03b2-elimination of cysteine-S conjugates and cysteine-Se conjugates. In this study, we performed mutational analyses of hKYAT1, targeting its catalytic, ligand-binding, and substrate-binding sites. The transamination activity of 13 mutant variants was systematically evaluated against sixteen different amino acid substrates, including kynurenine, selenomethionine (SeMet), and Se-methylselenocysteine (MSC), as well as for the \u03b2-elimination of SeMet and MSC. Our results demonstrate that mutations of residues E27 in the catalytic site and H279 in the substratestabilizing site significantly enhanced the transamination of several amino acids, including phenylalanine, tryptophan, histidine, and MSC. The H279F mutation increased transamination and \u03b2-elimination of MSC by 2- and 1.5-fold, respectively. Furthermore, mutation at the ligand-binding residues R398, F125, and N185 substantially reduced MSC transamination activity of hKYAT1. Interestingly, none of the tested mutations affected the transamination of l-kynurenine, a natural substrate of hKYAT1. Altogether, these findings support future investigation into hKYAT1 as a modifiable target in selenium-mediated anticancer approaches.", "doi": "10.1042/BCJ20253178", "pmid": "40785633", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12493182"}, {"db": "pii", "key": "236366"}], "notes": [], "created": "2026-08-20T09:28:22.125Z", "modified": "2026-08-20T09:28:22.422Z"}, {"entity": "publication", "iuid": "e09b19d3e5094597b9ab77bfc8a50ea0", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e09b19d3e5094597b9ab77bfc8a50ea0.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e09b19d3e5094597b9ab77bfc8a50ea0"}}, "title": "A Novel mRNA-Mediated and MicroRNA-Guided Approach to Specifically Eradicate Drug-Resistant Hepatocellular Carcinoma Cell Lines by Se-Methylselenocysteine.", "authors": [{"family": "Selvam", "given": "Arun Kumar", "initials": "AK", "orcid": "0000-0002-9854-2048", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8e7a8d1d439a4ed0aebad8389a7253e2.json"}}, {"family": "Jawad", "given": "Rim", "initials": "R"}, {"family": "Gramignoli", "given": "Roberto", "initials": "R", "orcid": "0000-0003-3362-4170", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a68ade86efde42e89d9e76ae394bac43.json"}}, {"family": "Achour", "given": "Adnane", "initials": "A", "orcid": "0000-0003-0432-710X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/65fba324156a4fcbafbe636e642587a9.json"}}, {"family": "Salter", "given": "Hugh", "initials": "H"}, {"family": "Bj\u00f6rnstedt", "given": "Mikael", "initials": "M", "orcid": "0000-0003-2831-3837", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/08e79d991fab47c18b7390c7ddc12963.json"}}], "type": "journal article", "published": "2021-07-07", "journal": {"title": "Antioxidants (Basel)", "issn": "2076-3921", "volume": "10", "issue": "7", "issn-l": null}, "abstract": "Despite progress in the treatment of non-visceral malignancies, the prognosis remains poor for malignancies of visceral organs and novel therapeutic approaches are urgently required. We evaluated a novel therapeutic regimen based on treatment with Se-methylselenocysteine (MSC) and concomitant tumor-specific induction of Kynurenine aminotransferase 1 (KYAT1) in hepatocellular carcinoma (HCC) cell lines, using either vector-based and/or lipid nanoparticle-mediated delivery of mRNA. Supplementation of MSC in KYAT1 overexpressed cells resulted in significantly increased cytotoxicity, due to ROS formation, as compared to MSC alone. Furthermore, microRNA antisense-targeted sites for miR122, known to be widely expressed in normal hepatocytes while downregulated in hepatocellular carcinoma, were added to specifically limit cytotoxicity in HCC cells, thereby limiting the off-target effects. KYAT1 expression was significantly reduced in cells with high levels of miR122 supporting the concept of miR-guided induction of tumor-specific cytotoxicity. The addition of alpha-ketoacid favored the production of methylselenol, enhancing the cytotoxic efficacy of MSC in HCC cells, with no effects on primary human hepatocytes. Altogether, the proposed regimen offers great potential to safely and specifically target hepatic tumors that are currently untreatable.", "doi": "10.3390/antiox10071094", "pmid": "34356326", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8301172"}, {"db": "pii", "key": "antiox10071094"}], "notes": [], "created": "2026-08-20T13:38:24.049Z", "modified": "2026-08-20T13:38:24.268Z"}, {"entity": "publication", "iuid": "fa59c1ce0746481a8a46dc75496f8b1b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/fa59c1ce0746481a8a46dc75496f8b1b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/fa59c1ce0746481a8a46dc75496f8b1b"}}, "title": "Targeted enzyme assisted chemotherapy (TEAC) \u2013 a novel microRNA-guided and selenium-based regimen to specifically eradicate hepatocellular carcinoma", "authors": [{"family": "Selvam", "given": "Arun Kumar", "initials": "AK", "orcid": "0000-0002-9854-2048", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8e7a8d1d439a4ed0aebad8389a7253e2.json"}}, {"family": "Jawad", "given": "Rim", "initials": "R"}, {"family": "Gramignoli", "given": "Roberto", "initials": "R"}, {"family": "Achour", "given": "Adnane", "initials": "A"}, {"family": "Salter", "given": "Hugh", "initials": "H"}, {"family": "Bj\u00f6rnstedt", "given": "Mikael", "initials": "M", "orcid": "0000-0003-2831-3837", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/08e79d991fab47c18b7390c7ddc12963.json"}}], "type": "posted-content", "published": "2021-02-12", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2021.02.09.430426", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T10:02:39.019Z", "modified": "2026-08-20T10:02:39.079Z"}]}