The ferrous-oxy complex of human aromatase.

Grinkova YV, Denisov IG, Waterman MR, Arase M, Kagawa N, Sligar SG
Biochem Biophys Res Commun. 2008 372 (2): 379-82

PMID: 18482580 · PMCID: PMC2478517 · DOI:10.1016/j.bbrc.2008.05.011

In this communication, we document the self-assembly of heterologously expressed truncated human aromatase (CYP19) into nanometer scale phospholipids bilayers (Nanodiscs). The resulting P450 CYP19 preparation is stable and can tightly associate with the substrate androstenedione to form a nearly complete high-spin ferric protein. Ferrous CYP19 in Nanodiscs was mixed anaerobically in a rapid-scan stopped-flow with atmospheric dioxygen and the formation of the ferrous-oxy complex observed. First order decay of the oxy-complex to release superoxide and regenerate the ferric enzyme was monitored kinetically. Surprisingly, the ferrous-oxy complex of aromatase is more stable than that of hepatic CYP3A4, opening the path to precisely determine the biochemical and biophysical properties of the reaction cycle intermediates in this important human drug target.

MeSH Terms (8)

Androstenedione Aromatase Humans Iron Lipid Bilayers Nanostructures Oxidation-Reduction Phospholipids

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