Lipocalin-type prostaglandin D synthase (β-trace) is a newly recognized type of retinoid transporter

Abstract

Lipocalin-type prostaglandin D synthase is responsible for the biosynthesis of prostaglandin De in the central nervous system and the genital organs and is secreted into the cerebrospinal fluid and the seminal plasma as β-trace. Here we analyzed retinoids binding of the enzyme by monitoring the fluorescence quenching of an intrinsic tryptophan residue, and appearance of circular dichroism around 330 nm, and a red shift of the UV absorption spectra of retinoids. We found that the enzyme binds all-trans- or 9-cis-retinoic acid and all-trans- or 13-cis-retinal, but not all-trans- retinol, with affinities (K(d) of 70-80 nM) sufficient for function as a retinoid transporter. All-trans-retinoic acid inhibited the enzyme activity in a noncompetitive manner, suggesting that it binds to the same hydrophobic pocket as prostaglandin H2, the substrate for prostaglandin D synthase, but at a different site in this pocket. It is likely that this enzyme is a bifunctional protein that acts as both retinoid transporter and prostaglandin D2-producing enzyme.