Snapshots of the Catalytic Cycle of an O2 , Pyridoxal Phosphate-Dependent Hydroxylase

ACS Chemical Biology
Jason B HedgesKatherine S Ryan

Abstract

Enzymes that catalyze hydroxylation of unactivated carbons normally contain heme and nonheme iron cofactors. By contrast, how a pyridoxal phosphate (PLP)-dependent enzyme could catalyze such a hydroxylation was unknown. Here, we investigate RohP, a PLP-dependent enzyme that converts l-arginine to ( S)-4-hydroxy-2-ketoarginine. We determine that the RohP reaction consumes oxygen with stoichiometric release of H2O2. To understand this unusual chemistry, we obtain ∼1.5 Å resolution structures that capture intermediates along the catalytic cycle. Our data suggest that RohP carries out a four-electron oxidation and a stereospecific alkene hydration to give the ( S)-configured product. Together with our earlier studies on an O2, PLP-dependent l-arginine oxidase, our work suggests that there is a shared pathway leading to both oxidized and hydroxylated products from l-arginine.

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Citations

Sep 6, 2018·Natural Product Reports·Yi-Ling Du, Katherine S Ryan
Jun 25, 2019·Angewandte Chemie·Jason B Hedges, Katherine S Ryan
Mar 7, 2020·The FEBS Journal·Elesha R HoffarthKatherine S Ryan
Nov 19, 2018·Current Opinion in Chemical Biology·Yasuhisa Asano, Kazuyuki Yasukawa
Jul 13, 2019·Journal of the American Chemical Society·Jin GuoKatherine S Ryan

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