10AL

indoleacetate decarboxylase with bound indole-3-acetate

Summary for 10AL

• Entry DOI: 10.2210/pdb10al/pdb
• EMDB information: 75028
• Descriptor: Formate C-acetyltransferase, 1H-INDOL-3-YLACETIC ACID (3 entities in total)
• Functional Keywords: glycyl radical enzyme, decarboxylase, anaerobic, lyase
• Biological source: Olsenella uli DSM 7084
• Total number of polymer chains: 4
• Total formula weight: 406239.61

Authors

Imrich, C.N.,Drennan, C.L. (deposition date: 2026-01-08, release date: 2026-09-16, Last modification date: 2026-09-30)

Primary citation

Imrich, C.N.,Backman, L.R.F.,Allworth, A.P.,Andorfer, M.C.,Paris, J.C.,Greeley, N.M.,Fu, B.,Balskus, E.P.,Drennan, C.L.
The structural basis of malodorant skatole formation by the glycyl radical enzyme indoleacetate decarboxylase.
Proc.Natl.Acad.Sci.USA, 123:e2618341123-e2618341123, 2026

PubMed Abstract: 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-Å resolution structure of IAD from the gut bacterium . 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 DO 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's 3'-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.

PubMed: 42758728
DOI: 10.1073/pnas.2618341123

Experimental method

ELECTRON MICROSCOPY (2.45 Å)