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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,22]]},"abstract":"<jats:p>\n                    Glycyl radical enzymes (GREs) catalyze challenging chemical reactions using a posttranslationally installed glycyl radical cofactor. One such enzyme, indoleacetate decarboxylase (IAD), performs the radical-based decarboxylation of indole-3-acetate (I3A) to form the malodorant molecule skatole. In addition to being an odor nuisance, skatole is a human and livestock lung toxin, a suspected carcinogen, and a mosquito attractant, all of which impact human health, agriculture, food production, and wastewater treatment. Here, we use cryogenic electron microscopy to solve a 2.45-\u00c5 resolution structure of IAD from the gut bacterium\n                    <jats:italic toggle=\"yes\">Olsenella uli<\/jats:italic>\n                    . We observe IAD in a homotetrameric form with the substrate I3A bound in all four protomers. The positioning of I3A in the active site is unexpected and is more consistent with a Kolbe-type decarboxylation mechanism, i.e., a decarboxylation initiated by a 1-electron oxidation of the carboxylate moiety rather than being initiated by hydrogen atom transfer (HAT). Previously, a high deuterium content in skatole from IAD assays in D\n                    <jats:sub>2<\/jats:sub>\n                    O was used to support a HAT mechanism over a Kolbe-type mechanism. However, we show here that deuterium content does not necessarily inform on mechanism as IAD can catalyze the exchange of skatole\u2019s 3\u2032-methyl hydrogens postturnover. Structural comparisons show that both IAD and hydroxyphenylacetate decarboxylase display structural features that are not found in other characterized GREs, suggesting that they represent a distinct GRE-subclass. Collectively, these insights will inform IAD inhibitor design aimed at decreasing skatole production.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2618341123","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:35:06Z","timestamp":1789752906000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["The structural basis of malodorant skatole formation by the glycyl radical enzyme indoleacetate decarboxylase"],"prefix":"10.1073","volume":"123","author":[{"given":"Christa N.","family":"Imrich","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042nb2s44","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Massachusetts Institute of Technology","place":["Cambridge"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0323-1336","authenticated-orcid":false,"given":"Lindsey R. 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