(A) Phyre2 structural homology models predict that
asparagine-47 interacts with the FMN in Rha1 (left) and tyrosine-195
coordinates NADPH in Rha2 (right). (B) Rates of NADPH
oxidation (200 µM) by WT (blue) and mutant (orange) variants of Rha1 and
Rha2 in the presence of 4-HNE. (C) Rate of NADPH oxidation
(200 µM) by human enzyme AKR1C1 in the presence of 4-HNE.
(D) NADPH oxidation rate by Rha1 and Rha2 in the
presence of 640 µM final concentration of various aldehydes.
(E) TLC plates showing the migration of reaction
contents of Lane 1: 4-HNE, Lane 2: 1,4-DHN, and Lanes 3–6: indicated
enzymes with 4-HNE in the absence and presence of NADPH after 1 hr of
reaction at room temperature. 4-HNE -- black arrow, 4-HNA -- red arrow,
1,4-DHN -- blue arrow. (F) Diagram of 4-HNE to 4-HNA
conversion. Data in (B), (C), (D)
and (E) are representative of at least three independent
experiments.