Skip to main content
Physical/Tech

The structural basis of malodorant skatole formation by the glycyl radical enzyme indoleacetate decarboxylase.

| Source: Proceedings of the National Academy of Sciences of the United States of America

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 wa

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 Olsenella uli . 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 2 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'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.

Read the original source →

Related Stories

Physical/Tech

Mark A. Ratner (1942-2026): Founded molecular electronics while spearheading the growth of science at Northwestern University.

Recently, we lost one of the original developers of the field of molecular electronics. Mark A. Ratner wrote a famous paper in 1974 that developed the theoretical framework for making a molecule act as a rectifier. This idea, and a host of further ideas that were stimulated by this and other papers, led to a huge amount of experimental and theoretical studies that continue to this day. But Mark's career was much more than that, with leadership at Northwestern University and beyond that continues

Continue reading
Physical/Tech

Historical trends show more declining than increasing species among European pollinators.

Anthropogenic global change presents a growing threat to insect pollinators. Yet, long-term, continental-scale assessments of their population trends remain limited. Here, we leveraged a curated database of over four million occurrence records, covering 88% of extant bee and hoverfly species in Europe, to assess persistence, richness, and occupancy trends over the past century. Species persistence at the European level was relatively high, with modern records available for 87% of bee and 89% of

Continue reading
Physical/Tech

The ABCD hypothesis.

If [Formula: see text] and [Formula: see text] are cardinals, then the cardinal exponentiation [Formula: see text] is the set of all functions from [Formula: see text] into [Formula: see text]. The ABCD hypothesis is the statement that for all infinite cardinals [Formula: see text] and [Formula: see text], [Formula: see text] if and only if [Formula: see text] and [Formula: see text]. The Axiom of Determinacy, AD, states that every two-player infinite game on [Formula: see text] has a winning st

Continue reading
Physical/Tech

Designing school choice for diversity in the San Francisco Unified School District

More than 65 years after the Brown v. Board of Education ruling that school segregation is unconstitutional, public schools across the United States are again experiencing rising segregation. In districts like San Francisco, efforts to implement district-wide choice policies have largely failed to reverse these trends. Since 2019, we have collaborated with the San Francisco Unified School District to design a student assignment policy meeting the district’s goals of diversity, predictability, an

Continue reading
Physical/Tech

On-site, subannual climate records decouple Neolithic expansion from climate instability

How the life of prehistoric people was influenced by climate change and extreme events often remains elusive. Finding appropriate spatiotemporal scales is the major challenge for studies with socioenvironmental questions. This challenge can be overcome by sourcing climatic information from archaeological sites, alongside traces of human agency. For instance, extreme cold-events have been proposed as causing a standstill in early farming expansion across the Mediterranean 8600-8000 years ago. How

Continue reading