{"entity": "researcher", "timestamp": "2026-09-28T23:51:13.615Z", "family": "Morgenstern", "given": "Ralf", "initials": "R", "orcid": "0000-0001-9094-0554", "affiliations": ["Institute of Environmental Medicine, Karolinska Institutet , SE-171 77 Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/1814990a0e1b437bb40b0371849dde6c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/1814990a0e1b437bb40b0371849dde6c"}}, "publications": [{"entity": "publication", "iuid": "79f23bbf7d5d404e88f576faa35621f6", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/79f23bbf7d5d404e88f576faa35621f6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/79f23bbf7d5d404e88f576faa35621f6"}}, "title": "Global Kinetic Mechanism of Microsomal Glutathione Transferase 1 and Insights into Dynamic Enzyme Activation.", "authors": [{"family": "Spahiu", "given": "Linda", "initials": "L"}, {"family": "\u00c5lander", "given": "Johan", "initials": "J"}, {"family": "Ottosson-Wadlund", "given": "Astrid", "initials": "A"}, {"family": "Svensson", "given": "Richard", "initials": "R"}, {"family": "Lehmer", "given": "Carina", "initials": "C"}, {"family": "Armstrong", "given": "Richard N", "initials": "RN"}, {"family": "Morgenstern", "given": "Ralf", "initials": "R", "orcid": "0000-0001-9094-0554", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1814990a0e1b437bb40b0371849dde6c.json"}}], "type": "journal article", "published": "2017-06-20", "journal": {"title": "Biochemistry", "issn": "1943-295X", "volume": "56", "issue": "24", "pages": "3089-3098", "issn-l": "0006-2960"}, "abstract": "Microsomal glutathione transferase 1 (MGST1) has a unique ability to be activated, \u226430-fold, by modification with sulfhydryl reagents. MGST1 exhibits one-third-of-the-sites reactivity toward glutathione and hence heterogeneous binding to different active sites in the homotrimer. Limited turnover stopped-flow kinetic measurements of the activated enzyme allowed us to more accurately determine the KD for the \"third\" low-affinity GSH binding site (1.4 \u00b1 0.3 mM). The rate of thiolate formation, k2 (0.77 \u00b1 0.06 s-1), relevant to turnover, could also be determined. By deriving the steady-state rate equation for a random sequential mechanism for MGST1, we can predict KM, kcat, and kcat/KM values from these and previously determined pre-steady-state rate constants (all determined at 5 \u00b0C). To assess whether the pre-steady-state behavior can account for the steady-state kinetic behavior, we have determined experimental values for kinetic parameters at 5 \u00b0C. For reactive substrates and the activated enzyme, data for the microscopic steps account for the global mechanism of MGST1. For the unactivated enzyme and more reactive electrophilic substrates, pre-steady-state and steady-state data can be reconciled only if a more active subpopulation of MGST1 is assumed. We suggest that unactivated MGST1 can be partially activated in its unmodified form. The existence of an activated subpopulation (approximately 10%) could be demonstrated in limited turnover experiments. We therefore suggest that MSGT1 displays a preexisting dynamic equilibrium between high- and low-activity forms.", "doi": "10.1021/acs.biochem.7b00285", "pmid": "28558199", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS964830"}, {"db": "pmc", "key": "PMC5954419"}], "notes": [], "created": "2018-12-05T12:59:03.462Z", "modified": "2026-09-23T12:54:43.903Z"}]}