The expression “catalytic reversibility” describes the situation where a bidirectional molecular redox catalyst can function in either direction of the reaction under near equilibrium conditions, as o...

[FeFe] hydrogenases are highly efficient metalloenzymes that catalyze hydrogen conversion via a sophisticated active site cofactor known as the H-cluster. Biosynthesis of its [2Fe]H subcluster, which ...

Nature - Computer approach creates synthetic enzymes 100 times more efficient than those designed by AI.

Radical SAM enzymes are the most widespread biocatalysts. These metalloenzymes, using S-adenosyl-l-methionine (SAM) and a [4Fe-4S] cluster as central cofactors, catalyze a broad range of chemically ch...

Radical SAM enzymes are the most widespread biocatalysts. These metalloenzymes, using S-adenosyl-l-methionine (SAM) and a [4Fe-4S] cluster as central cofactors, catalyze a broad range of chemically challenging transformations. The vast majority of radical SAM enzymes initiate their reaction by the homolytic cleavage of the SAM C5′–S bond and the generation of the central 5′-deoxyadenosyl radical (5′-dA·). In this study, by combining spectroscopic approaches with labeling and biochemical analyses, we show that ArsL, the key enzyme in the biosynthesis of the arsenic-containing antibiotic arsinothricin, catalyzes a unique reaction: the addition of the 3-amino-3-carboxypropyl radical (ACP·) to As(III). Remarkably, by exploiting several radical trapping strategies, we demonstrate that in sharp contrast to canonical radical SAM enzymes ArsL cleaves the SAM Cγ-S bond. In addition, using electron paramagnetic resonance (EPR) and hyperfine sublevel correlation (HYSCORE) spectroscopies, we establish that ArsL has a unique SAM binding mode, consistent with its catalytic properties and predicted structure. Notably, EPR and HYSCORE analyses support that SAM interacts with the radical SAM [4Fe-4S] cluster in an uncharacteristic conformation to form ACP·. Collectively, our study reveals that members of the superfamily of radical SAM enzymes are able to finely tune the binding of the SAM cofactor in order to perform unique chemistries.

A protein language model enables structure prediction and analysis of more than 600 million metagenomic proteins.

Antibiotic resistance presents a growing global health crisis, demanding new therapeutic strategies that target novel bacterial mechanisms. Recent advances in protein structure prediction and machine ...

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This study shows that only those dual-targeting antibiotics limit resistance in Gram-negative pathogens that also target the membrane of the bacteria. This mechanism provides a basis for designing fut...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019, can infect the gastrointestinal (GI) tract, and individuals who exhibit GI symptoms of...